Main Strategic Applications of Named Reactions in Organic Synthesis

Strategic Applications of Named Reactions in Organic Synthesis

,
Kurti and Czako have produced an indispensable tool for specialists and non-specialists in organic chemistry. This innovative reference work includes 250 organic reactions and their strategic use in the synthesis of complex natural and unnatural products. Reactions are thoroughly discussed in a convenient, two-page layout-using full color. Its comprehensive coverage, superb organization, quality of presentation, and wealth of references, make this a necessity for every organic chemist.* The first reference work on named reactions to present colored schemes for easier understanding* 250 frequently used named reactions are presented in a convenient two-page layout with numerous examples* An opening list of abbreviations includes both structures and chemical names* Contains more than 10,000 references grouped by seminal papers, reviews, modifications, and theoretical works* Appendices list reactions in order of discovery, group by contemporary usage, and provide additional study tools* Extensive index quickly locates information using words found in text and drawings
Year: 2005
Edition: 1
Publisher: Academic Press
Language: english
Pages: 810
ISBN 10: 0124297854
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Strategic Applications
of Named Reactions in
Organic Synthesis

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Strategic Applications
of Named Reactions in
Organic Synthesis
Background and
Detailed Mechanisms
by

László Kürti and Barbara Czakó
UNIVERSITY OF PENNSYLVANIA

250 Named Reactions

AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD • PARIS
SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO
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Senior Publishing Editor Jeremy Hayhurst
Project Manager Carl M. Soares
Editorial Assistant Desiree Marr
Marketing Manager Linda Beattie
Cover Printer RR Donnelley
Interior Printer RR Donnelley
Elsevier Academic Press
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This book is printed on acid-free paper.
Copyright © 2005, Elsevier Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any
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storage and retrieval system, without permission in writing from the publisher.
Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford,
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also complete your request on-line via the Elsevier homepage (http://elsevier.com), by selecting
“Customer Support” and then “Obtaining Permissions.”
Library of Congress Cataloging-in-Publication Data
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A catalogue record for this book is available from the British Library
ISBN: 0-12-429785-4
For all information on all Elsevier Academic Press Publications
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Printed in the United States of America
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This book is dedicated to
Professor Madeleine M. Joullié
for her lifelong commitment
to mentoring graduate students

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ABOUT THE AUTHORS

Barbara Czakó was born and raised in Hungary. She
received her Diploma from Lajos Kossuth University in
Debrecen, Hungary (now University of Debrecen). She
obtained her Master of Science degree at University of
Missouri-Columbia. Currently she is pursuing her Ph.D.
degree

in

synthetic

organic

chemistry

under

the

supervision of Professor Gary A. Molander at the
University of Pennsylvania.

László Kürti was born and raised in Hungary. He
received his Diploma from Lajos Kossuth University in
Debrecen, Hungary (now University of Debrecen). He
obtained his Master of Science degree at University of
Missouri-Columbia. Currently he is pursuing his Ph.D.
degree

in

synthetic

organic

chemistry

under

the

supervision of Professor Amos B. Smith III at the
University of Pennsylvania.

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ACKNOWLEDGEMENTS
The road that led to the completion of this book was difficult, however, we enjoyed the support of
many wonderful people who guided and helped us along the way. The most influential person was
Professor Madeleine M. Joullié whose insight, honest criticism and invaluable suggestions helped to
mold the manuscript into its current form.
When we completed half of the manuscript in early 2004, Professor Amos B. Smith III was
teaching his synthesis class "Strategies and Tactics in Organic Synthesis" and adopted the manuscript.
We would like to thank him for his support and encouragement. We also thank the students in his class
for their useful observations that aided the design of a number of difficult schemes.
Our thanks also go to Professor Gary A. Molander for his valuable remarks regarding the
organometallic reactions. He had several excellent suggestions on which named reactions to include.
Earlier this year our publisher, Academic Press/Elsevier Science, sent the manuscript to a
number of research groups in the US as well as in the UK. The thorough review conducted by the
professors and in some cases also by volunteer graduate students is greatly appreciated.
They are (in alphabetical order):
Professor Donald H. Aue (University of California
Santa Barbara)
Professor Ian Fleming (University of Cambridge,
UK)
Professor Rainer Glaser (University of MissouriColumbia)
Professor Michael Harmata (University of MissouriColumbia)

Professor Robert A. W. Johnstone (University of
Liverpool, UK)
Professor Erik J. Sorensen (Princeton University)
Professor P. A. Wender (Stanford University) and
two of his graduate students Cindy Kan and John
Kowalski
Professor Peter Wipf (University of Pittsburgh)

We would like to express our gratitude to the following friends/colleagues who have carefully read
multiple versions of the manuscript and we thank them for the excellent remarks and helpful discussions.
They were instrumental in making the manuscript as accurate and error free as possible:
James P. Carey (Merck Research Laboratories)
Akin H. Davulcu (Bristol-Myers Squibb/University of
Pennsylvania)
Dr. Mehmet Kahraman (Kalypsys, Inc.)

Justin Ragains (University of Pennsylvania)
Thomas Razler (University of Pennsylvania)

There were several other friends/colleagues who reviewed certain parts of the manuscript or
earlier versions and gave us valuable feedback on the content as well as in the design of the schemes.
Clay Bennett (University of Pennsylvania)
Prof. Cheon-Gyu Cho (Hanyang University,
Korea/University of Pennsylvania)
Dr. Shane Foister (University of Pennsylvania)
Dr. Eugen Mesaros (University of Pennsylvania)

Dr. Emmanuel Meyer (University of Pennsylvania)
David J. St. Jean, Jr. (University of Pennsylvania)
Dr. Kirsten Zeitler (University of Regensburg,
Germany)

Finally, we would like to thank our editor at Elsevier, Jeremy Hayhurst, who gave us the chance
to make a contribution to the education of graduate students in the field of organic chemistry. He
generously approved all of our requests for technical support thus helping us tremendously to finish the
writing in a record amount of time. Our special thanks are extended to editorial assistants Desireé Marr
and previously, Nora Donaghy, who helped conduct the reviews and made sure that we did not get lost
in a maze of documents.

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CONTENTS

I.

Foreword by E.J. Corey.................................................................................................... x

II.

Introduction by K.C. Nicolaou ......................................................................................... xi

III.

Preface ............................................................................................................................xii

IV.

Explanation of the Use of Colors in the Schemes and Text ..........................................xiv

V.

List of Abbreviations ..................................................................................................xvii

VI.

List of Named Organic Reactions................................................................................xlv

VII.

Named Organic Reactions in Alphabetical Order ........................................................ 1

VIII.

Appendix: Listing of the Named Reactions by Synthetic Type and by their Utility...... 502
8.1 Brief explanation of the organization of this section.............................................. 502
8.2 List of named reactions in chronological order of their discovery.......................... 503
8.3 Reaction categories – Categorization of named reactions in tabular format......... 508
8.4 Affected functional groups – Listing of transformations in tabular format.............. 518
8.5 Preparation of functional groups – Listing of transformations in tabular format .... 526

IX.

References................................................................................................................... 531

X.

Index............................................................................................................................. 715

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FOREWORD
This book on "Strategic Applications of Named Reactions in Organic Synthesis"
is destined to become unusually useful, valuable, and influential for advanced students
and researchers in the field. It breaks new ground in many ways and sets an admirable
standard for the next generation of texts and reference works. Its virtues are so
numerous there is a problem in deciding where to begin. My first impression upon
opening the book was that the appearance of its pages is uniformly elegant and pleasing
– from the formula graphics, to the print, to the layout, and to the logical organization and
format. The authors employ four-color graphics in a thoughtful and effective way. All the
chemical formulas are exquisitely drawn.
The book covers many varied and useful reactions for the synthesis of complex
molecules, and in a remarkably clear, authoritative and balanced way, considering that
only two pages are allocated for each. This is done with unusual rigor and attention to
detail. Packed within each two-page section are historical background, a concise
exposition of reaction mechanism and salient and/or recent applications. The context of
each example is made crystal clear by the inclusion of the structure of the final synthetic
target. The referencing is eclectic but extensive and up to date; important reviews are
included.
The amount of information that is important for chemists working at the frontiers
of synthesis to know is truly enormous, and also constantly growing. For a young chemist
in this field, there is so much to learn that the subject is at the very least daunting. It
would be well neigh impossible were it not for the efforts of countless authors of
textbooks and reviews. This book represents a very efficient and attractive way forward
and a model for future authors. If I were a student of synthetic chemistry, I would read
this volume section by section and keep it close at hand for reference and further study.
I extend congratulations to László Kürti and Barbara Czakó for a truly fine
accomplishment and a massive amount of work that made it possible. The scholarship
and care that they brought to this task will be widely appreciated because they leap out of
each page. I hope that this wonderful team will consider extending their joint venture to
other regions of synthetic chemical space. Job well done!

E. J. Corey
January, 2005

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INTRODUCTION
The field of chemical synthesis continues to amaze with its growing and
impressive power to construct increasingly complex and diverse molecular architectures.
Being the precise science that it is, this discipline often extends not only into the realms
of technology, but also into the domains of the fine arts, for it engenders unparallel
potential for creativity and imagination in its practice. Enterprises in chemical synthesis
encompass both the discovery and development of powerful reactions and the invention
of synthetic strategies for the construction of defined target molecules, natural or
designed, more or less complex. While studies in the former area –synthetic
methodology– fuel and enable studies in the latter –target synthesis– the latter field offers
a testing ground for the former. Blending the two areas provides for an exciting endeavor
to contemplate, experience, and watch. The enduring art of total synthesis, in particular,
affords the most stringent test of chemical reactions, old and new, named and unnamed,
while its overall reach and efficiency provides a measure of its condition at any given
time. The interplay of total synthesis and its tools, the chemical reactions, is a fascinating
subject whether it is written, read, or practiced.
This superb volume by László Kürti and Barbara Czakó demonstrates clearly the
power and beauty of this blend of science and art. The authors have developed a
standard two-page format for discussing each of their 250 selections whereby each
named reaction is concisely introduced, mechanistically explained, and appropriately
exemplified with highlights of constructions of natural products, key intermediates and
other important molecules. These literature highlights are a real treasure trove of
information and a joy to read, bringing each named reaction to life and conveying a
strong sense of its utility and dynamism. The inclusion of an up-to-date reference listing
offers a complete overview of each reaction at one’s fingertips.
The vast wealth of information so effectively compiled in this colorful text will not
only prove to be extraordinarily useful to students and practitioners of the art of chemical
synthesis, but will also help facilitate the shaping of its future as it moves forward into
ever higher levels of complexity, diversity and efficiency. The vitality of the enduring field
of total synthesis exudes from this book, captivating the attention of the reader
throughout. The authors are to be congratulated for the rich and lively style they
developed and which they so effectively employed in their didactic and aesthetically
pleasing presentations. The essence of the art and science of synthesis comes alive from
the pages of this wonderful text, which should earn its rightful place in the synthetic
chemist’s library and serve as an inspiration to today’s students to discover, invent and
apply their own future named reactions. Our thanks are certainly due to László Kürti and
Barbara Czakó for a splendid contribution to our science.

K.C. Nicolaou
January, 2005

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PREFACE
Today’s organic chemist is faced with the challenge of navigating his or her way
through the vast body of literature generated daily. Papers and review articles are full of
scientific jargon involving the description of methods, reactions and processes defined by
the names of the inventors or by a well-accepted phrase. The use of so-called “named
reactions” plays an important role in organic chemistry. Recognizing these named
reactions and understanding their scientific content is essential for graduate students and
practicing organic chemists.
This book includes some of the most frequently used named reactions in organic
synthesis. The reactions were chosen on the basis of importance and utility in synthetic
organic chemistry. Our goal is to provide the reader with an introduction that includes a
detailed mechanism to a given reaction, and to present its use in recent synthetic
examples. This manuscript is not a textbook in the classical sense: it does not include
exercises or chapter summaries. However, by describing 250 named organic reactions
and methods with an extensive list of leading references, the book is well-suited for
independent or classroom study. On one hand, the compiled information for these
indispensable reactions can be used for finding important articles or reviews on a given
subject. On the other hand, it can also serve as supplementary material for the study of
organic reaction mechanisms and synthesis.
This book places great emphasis on the presentation of the material. Drawings
are presented accurately and with uniformity. Reactions are listed alphabetically and
each named reaction is presented in a convenient two-page layout. On the first page, a
brief introduction summarizes the use and importance of the reaction, including
references to original literature and to all major reviews published after the primary
reference. When applicable, leading references to modifications and theoretical studies
are also given. The introduction is followed by a general scheme of the reaction and by a
detailed mechanism drawn using a four-color code (red, blue, green and black) to ensure
easy understanding. The mechanisms always reflect the latest evidence available for the
given reaction. If the mechanism is unknown or debatable, references to the relevant
studies are included. The second page contains 3 or 4 recent synthetic examples utilizing
the pertinent named reaction. In most cases the examples are taken from a synthetic
sequence leading to the total synthesis of an important molecule or a natural product.
Some examples are taken from articles describing novel methodologies. The synthetic
sequences are drawn using the four-color code, and the procedures are described briefly
in 2-3 sentences. If a particular named reaction involves a complex rearrangement or the
formation of a polycyclic ring system, numbering of the carbon-skeleton is included in
addition to the four-color code. In the depicted examples, the reaction conditions as well
as the ratio of observed isomers (if any) and the reported yields are shown. The target of

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the particular synthetic effort is also illustrated with colors indicating where the
intermediates reside in the final product.
The approach used in this book is also unique in that it emphasizes the clever
use of many reactions that might otherwise have been overlooked.
The almost 10,000 references are indexed at the end of the book and include the
title of the cited book, book section, chapter, journal or review article. The titles of seminal
papers written in a foreign language were translated to English. The name of the author
of a specific synthetic example was chosen as the one having an asterisk in the
reference.
In order to make the book as user-friendly as possible, we have included a
comprehensive list of abbreviations used in the text or drawings along with the structure
of the protecting groups and reagents. Also in an appendix, the named organic reactions
are grouped on the basis of their use in contemporary synthesis. Thus the reader can
readily

ascertain

which

named

organic

reactions

effect

the

same

synthetic

transformations or which functional groups are affected by the use of a particular named
reaction. Finally, an index is provided to allow rapid access to desired information based
on keywords found in the text or the drawings.

László Kürti & Barbara Czakó
University of Pennsylvania
Philadelphia, PA
January 2005

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IV. EXPLANATION OF THE USE OF COLORS
IN THE SCHEMES AND TEXT
The book uses four colors (black, red, blue, and green) to depict the synthetic and mechanistic schemes and highlight
certain parts of the text. In the “Introduction” and “Mechanism” sections of the text, the title named reaction/process
is highlighted in blue and typed in italics:
“The preparation of ketones via the C-alkylation of esters of 3-oxobutanoic acid
(acetoacetic esters) is called the acetoacetic ester synthesis. Acetoacetic esters
can be deprotonated at either the C2 or at both the C2 and C4 carbons,
depending on the amount of base used.”
All other named reactions/processes that are mentioned are typed in italics:
“Dilute acid hydrolyzes the ester group, and the resulting β-keto acid undergoes
decarboxylation to give a ketone (mono- or disubstituted acetone derivative),
while aqueous base induces a retro-Claisen reaction to afford acids after
protonation.”
In the “Synthetic Applications” section, the name of the target molecule is highlighted in blue:
“During the highly stereoselective total synthesis of epothilone B by J.D. White
and co-workers, the stereochemistry of the alcohol portion of the macrolactone
was established by applying Davis’s oxaziridine oxidation of a sodium enolate.”
In the schemes, colors are applied to highlight the changes in a given molecule or intermediate (formation and
breaking of bonds). It is important to note that due to the immense diversity of reactions, it is impossible to implement
a strictly unified use of colors. Therefore, each scheme has a unique use of colors specifically addressing the
given transformation. By utilizing four different colors the authors’ goal is to facilitate understanding. The authors
hope that the readers will look up the cited articles and examine the details of a given synthesis. The following
sample schemes should help the readers to understand how colors are used in this book.
•

In most (but not all) schemes the starting molecule is colored blue, while the reagent or the reaction partner may
be of any of the remaining two colors (red and green). The newly formed bonds are always black.
new bond
BnO

BnO
O

Zn-Cu,
Et2O, 0 °C

BnO

Cl

O

Cl3CCOCl

Cl

BnO

O

OBn

OBn
new bond

•

The general schemes follow the same principle of coloring, and where applicable the same type of key reagents
are depicted using the same color. (In this example the two different metal-derived reagents are colored green.)
Simmons & Smith (1958):
R2

R2

CH2

Zn-Cu

R1
(Z)-1,2-disubstituted alkene

CH2I2 / ether

R1

R

R

1

R4
R3
substituted
alkene

non-coordinating
solvent

CH2I2 / ether

CH2
R1
1,2-trans-Disubstituted cyclopropane

Charette asymmetric modification (1994):
R5

H
Et2Zn / R5CHI2

Zn-Cu

R1
(E)-1,2-disubstituted
alkene

1,2-cis-Disubstituted
cyclopropane

Furukawa modification (1966):
2

R2

R2

R2

C

R6

HO
R1

R1

R4
R3
Substituted
cyclopropane

R2

+
R3

O

R6

B

Et2Zn
R5CHI2

O

DME/DCM

Bu
allylic alcohol dioxaborolane

R5

H
R1

C

OH

R2
R3
Optically active
cyclopropane

R1-4 = H, substituted alkyl and aryl; R5 = H, Me, phenyl; R6 = CONMe2; non-coordinating solvent: toluene, benzene, DCM, DCE

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The mechanistic schemes benefit the most from the use of four colors. These schemes also include extensive
arrow-pushing. The following two schemes demonstrate this point very well.
•

The catalytic cycle for the Suzuki cross-coupling:
LnPd(0)
R1 R 2

R2 X

reductive
elimination

oxidative
addition

R1 B(R)2

L

L(n-1)Pd(II)

M+(-OR)
base

+

organoborane

R1

X
LnPd(II)

R2

R2

OR
1

R

B(R)2

M+(-OR)

borate

transmetallation

metathesis

L + RO B(R)2
OR
LnPd(II)

•

M+(-X)

OR
R2

The mechanism of the Swern oxidation:

Activation of DMSO with TFAA:
O
F 3C

O
O

O
CF3

F3C

CH3

H 3C S

O S

CF3

O

O

< -30 °C

O

S CH3

O

CH3

R

F 3C

2

HO

CH3

O
O

R1

S

CH3

- CF3COOH

R1

O

H

H 3C

Activation of DMSO with oxalyl chloride:
O

H 3C

H 3C S

H 3C
Activation of the alcohol:
CH3
Cl S
HO
CH3
chlorosulfonium
salt

F 3C

S

CH2
O

O
side product

H

NEt3

H 3C

R1

S

CH2
R1

O

R2
alkoxysulfonium
ylide

R2
alkoxysulfonium
salt

O

CH3

- Cl

O

H 3C

S

O

Cl

R1

H
S

CH2

O
R

CH3
S

CH3

R

H 3C

- HCl

R1

O

S

S

H2
C

NEt3

H

R2

1

xv

S

C
H2

H

O
+

C +

R2
R1
Ketone or Aldehyde

CO

O

H3C

S
O

R1

O

H 3C

+

CH3
chlorosulfonium
salt

R2

H
2

Cl

O

R2

O

CH3

Cl

O

CH3

H 3C
Formation of the product:

Cl

Cl

S O

Pummerer
rearrangement

S

O

Cl
O

H2
C

O

R2

Cl

H 3C

trifluoroacetoxydimethylsulfonium trifluoroacetate

Activation of the alcohol:
F 3C

> -30 °C

CF3

O

CH3

CH3

CH3

CF3CO2
H 3C S O

O

CH2
R1

R2
alkoxysulfonium
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In the case of complex rearrangements, numbering of the initial carbon skeleton has been applied in addition to
the colors to facilitate understanding. Again, the newly formed bonds are black.

OH
5

4

OK
KH, 18-crown-6

3

6

HN 2

6

THF, r.t.

1

4

5

N2

N2

2-aza-Cope

1

OK
5

6

4

3

H

1

CN

•

[3,3]

3

In most instances, the product of a given named reaction/process will be part of a larger structure (e.g., natural
product) at the end of the described synthetic effort. For pedagogical reasons, the authors decided to indicate
where the building block appears in the target structure. It is the authors’ hope that the reader will be able to put
the named reaction/process in context and the provided synthetic example will not be just an abstract one.

OTHP

OTHP
1. NaHMDS, THF,
-78 °C

N

Bn

O
O

•

PhO2S

steps
OH

O

2.

O

N

Ph

3. CSA, THF, -78 °C
71% for 3 steps

O
N
O
O

O

S

Bn

OH

N
O
O
OH
Epothilone B

O

The references at the end of the book are listed in alphabetical order, and the named reaction for which the
references are listed is typed in blue and with boldface (see Dakin oxidation). Important: the references are
listed in chronological order when they appear as superscript numbers in the text (e.g., reference 10 is a
more recent paper than reference 12, but it received a smaller reference number because it was cited in the text
earlier).
Mechanism: 12,10,15-17
The mechanism of the Dakin oxidation is very similar to the mechanism of the Baeyer-Villiger oxidation.

•

For the Dakin oxidation example, the references at the end of the book will be printed in the order they have
been cited, but within a group of references (e.g., 15-17) they appear in chronological order.
Dakin oxidation
10. Hocking, M. B. Dakin oxidation of o-hydroxyacetophenone and some benzophenones. Rate enhancement and mechanistic aspects.
Can. J. Chem. 1973, 51, 2384-2392.
11. Matsumoto, M., Kobayashi, K., Hotta, Y. Acid-catalyzed oxidation of benzaldehydes to phenols by hydrogen peroxide. J. Org. Chem.
1984, 49, 4740-4741.
12. Ogata, Y., Sawaki, Y. Kinetics of the Baeyer-Villiger reaction of benzaldehydes with perbenzoic acid in aquo-organic solvents. J. Org.
Chem. 1969, 34, 3985-3991.
13. Boeseken, J., Coden, W. D., Kip, C. J. The synthesis of sesamol and of its β-glucoside. The Baudouin reaction. Rec. trav. chim. 1936,
55, 815-820.
14. Kabalka, G. W., Reddy, N. K., Narayana, C. Sodium percarbonate: a convenient reagent for the Dakin reaction. Tetrahedron Lett. 1992,
33, 865-866.
15. Hocking, M. B., Ong, J. H. Kinetic studies of Dakin oxidation of o- and p-hydroxyacetophenones. Can. J. Chem. 1977, 55, 102-110.
16. Hocking, M. B., Ko, M., Smyth, T. A. Detection of intermediates and isolation of hydroquinone monoacetate in the Dakin oxidation of phydroxyacetophenone. Can. J. Chem. 1978, 56, 2646-2649.
17. Hocking, M. B., Bhandari, K., Shell, B., Smyth, T. A. Steric and pH effects on the rate of Dakin oxidation of acylphenols. J. Org. Chem.
1982, 47, 4208-4215.

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V. LIST OF ABBREVIATIONS
Abbreviation

Chemical Name

Chemical Structure
O
O

O

18-Cr-6

18-crown-6
O

O
O

O

Ac

acetyl

acac

acetylacetonyl

AA
AD

asymmetric aminohydroxylation
asymmetric dihydroxylation

ad

adamantyl

O

O

NA
NA

O
N

ADDP

N N

1,1'-(azodicarbonyl)dipiperidine
N

O

ADMET

NA

acyclic diene metathesis polymerization

O

acaen

N

N,N’-bis(1-methyl-3-oxobutylidene)ethylenediamine

N

O

AIBN

2,2'-azo bisisobutyronitrile

Alloc

allyloxycarbonyl
O

Am

amyl (n-pentyl)

An

p-anisyl

ANRORC
aq

anionic ring-opening ring-closing
aqueous

O

NA
NA

O

AQN

anthraquinone
O

Ar

aryl (substituted aromatic ring)

xvii

N

N N

N

NA

O

TABLE OF CONTENTS

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Abbreviation

Chemical Name

Chemical Structure

ATD

aluminum tris(2,6-di-tert-butyl-4-methylphenoxide)

atm

1 atmosphere = 10 Pa (pressure)

O

Al

3
5

NA
Ph

ATPH

aluminum tris(2,6-diphenylphenoxide)

Al

O
Ph

BBN (9-BBN)

9-borabicyclo[3.3.1]nonane (9-BBN)

B

H

B

BCME

9-borabicyclo[3.3.1]nonyl

bis(chloromethyl)ether

3

B

Cl

O

Cl

O

BCN

BDPP

N-benzyloxycarbonyloxy-5-norbornene-2,3dicarboximide

(2R, 4R) or (2S, 4S) bis(diphenylphosphino)pentane

N O
O
O

O

Ph2P

PPh2
(R)

(R)

BER

NA

borohydride exchange resin

OH

BHT

2,6-di-t-butyl-p-cresol (butylated hydroxytoluene)

BICP

2(R)-2’(R)-bis(dipenylphosphino)-1(R),1’(R)dicyclopentane

BINAL-H

BINAP

2,2'-dihydroxy-1,1'-binaphthyl lithium aluminum
hydride

2,2'-bis(diphenylphosphino)-1,1'-binaphthyl

(R) (R)
(R)

(R)

Ph2P

PPh2

O
O

H
Al

Li
H

PPh2
PPh2

xviii

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Abbreviation

Chemical Name

BINOL

1,1'-bi-2,2'-naphthol

Chemical Structure

OH
OH

O
S

Bip

biphenyl-4-sulfonyl

bipy

2,2'-bipyridyl

BLA

Brönsted acid assisted chiral Lewis acid

bmin

1-butyl-3-methylimidazolium cation

BMS

Borane-dimethyl sulfide complex

Bn

benzyl

O

N

N

NA

N

N

H3B SMe2

O

BNAH

1-benzyl-1,4-dihydronicotinamide

BOB

4-benzyloxybutyryl

Boc

t-butoxycarbonyl

N

NH2

O

O

O

O

O

BOM

benzyloxymethyl

BOP-Cl

bis(2-oxo-3-oxazolidinyl)phosphinic chloride

O

O

Cl

O

P
N

N

O

O

NA

bp

boiling point

BPD

bis(pinacolato)diboron

O
O

B B

O
O
O

O

O

BPO

benzoyl peroxide

BPS (TBDPS)

t-butyldiphenylsilyl

O

Ph

Si

xix

Ph

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Abbreviation

Chemical Name

BQ

benzoquinone

Chemical Structure
O

O

O

Bs

brosyl =
(4-bromobenzenesulfonyl)

BSA

N,O-bis(trimethylsilyl)acetamide

BSA

Bovine serum albumin

Bt

1- or 2-benzotriazolyl

S

Br

O

O
Si

Si N

NA

N
N
N

F

BTAF

benzyltrimethylammonium fluoride

BTEA

benzyltriethylammonium

BTEAC

benzyltriethylammonium chloride

BTFP

3-bromo-1,1,1-trifluoro-propan-2-one

N

N

Cl
N

F

O

F
F
Br

BTMA

benzyltrimethylammonium

N

BTMSA

bis(trimethylsilyl) acetylene

Si

Si

O

BTS

bis(trimethylsilyl) sulfate

Si

O

benzothiazole 2-sulfonic acid

BTSP

bis(trimethylsilyl) peroxide

Bz

benzoyl

Bu ( Bu)

n

n-butyl

c

cyclo

S

HO S
N

O

Si

O

O

O

NA

xx

Si

O

O

BTSA

O

S

Si

TABLE OF CONTENTS

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Abbreviation

Chemical Name

Chemical Structure

ca

NA

CA

circa
(approximately)
chloroacetyl

CAN

cerium(IV) ammonium nitrate (cericammonium
nitrate)

Ce(NH4)2(NO3)6

cat.

catalytic

NA

CB

catecholborane

O

Cl

O
HB
O
H Ph

CBS

Corey-Bakshi-Shibata reagent
N B

Ph
R = H, alkyl

O

R

Cbz (Z)

O

benzyloxycarbonyl

O

cc. or conc.
CCE

NA

concentrated
constant current electrolysis

NA
O

CDI

carbonyl diimidazole

CHD

1,3 or 1,4-cyclohexadiene

N

N

N

1,3-CHD

N

1,4-CHD

Ph

CHIRAPHOS

2,3-bis(diphenylphosphino)butane

Ph

(S)

P

(S)

P
Ph

Ph

Chx (Cy)

cyclohexyl

Cl

CIP

2-chloro-1,3-dimethylimidazolidinium
hexafluorophosphate

CM (XMET)

cross metathesis

CMMP

cyanomethylenetrimethyl phosphorane

COD

1,5-cyclooctadiene

COT

1,3,5-cyclooctatriene

Cp

cyclopentadienyl

N

NH

PF6

NA

P

N

O
S O

CPTS

collidinium-p-toluenesulfonate

xxi

O

H N

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Abbreviation

Chemical Name

Chemical Structure

CRA

complex reducing agent

NA

Cr-PILC

chromium-pillared clay catalyst

NA

CSA

camphorsufonic acid
O

CSI

SO3H

O

chlorosulfonyl isocyanate

CTAB

cetyl trimethylammonium bromide

CTACl

cetyl trimethylammonium chloride

N

S

Cl

C

O

O

N

N

Cl

C15H31

CTAP

N

cetyl trimethylammonium permanganate

MnO4

C15H31

Δ
d

heat
days (length of reaction time)

DABCO

1,4-diazabicyclo[2.2.2]octane

NA
NA
N
N
N

N

F

DAST

diethylaminosulfur trifluoride

F S N
F

DATMP

diethylaluminum 2,2,6,6-tetramethylpiperidide

N
AlEt2

Ph

DBA (dba)

dibenzylideneacetone

Ph
O

O

DBAD

N

di-tert-butylazodicarboxylate
O

O
N
O

O

Br
N

DBI

dibromoisocyanuric acid

O

NH
N
Br

xxii

O

Br

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
O

DBM

O

dibenzoylmethane

9

DBN

1

1,5-diazabicyclo[4.3.0]non-5-ene

6

N

4

5

dibenzosuberyl

11

DBU

3

8
7

DBS

2

N

1,8-diazabicyclo[5.4.0]undec-7-ene

1

2

3

N

10
9

N

4

7

5
6

8

CN

DCA

9,10-dicyanoanthracene
CN
Cl

DCB

1,2-dichlorobenzene

DCC

dicyclohexylcarbodiimide

DCE

1,1-dichloroethane

Cl

N

C

N

Cl
Cl

DCM

CH2Cl2

dichloromethane

CN

DCN

1,4-dicyanonaphthalene
CN

Dcpm

dicyclopropylmethyl

DCU

N,N’-dicyclohexylurea

O
N
H

N
H
O

NC

DDQ

Cl

2,3-dichloro-5,6-dicyano-1,4-benzoquinone
NC

Cl
O

de

diastereomeric excess

xxiii

NA

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Abbreviation

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Chemical Name

Chemical Structure
O

DEAD

diethyl azodicarboxylate

O

N

N

O
O

DEIPS

diethylisopropylsilyl

DEPBT

3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin4(3H)-one

Si

N

O

O

DET

O

OEt
O
N
P

EtO

OH
O

(R)

diethyl tartrate

N

(R)

O
HO

DHP

O

3,4-dihydro-2H-pyran
O

OMe

DHQ

H

dihydroquinine

OH
N

N

H

Et

Et
N

(DHQ)2PHAL

H

bis(dihydroquinino)phthalazine

H

N

N N
O

O

H
H

MeO

OMe
N

N

OMe

DHQD

dihydroquinidine

H

N
OH
H

N

Et

Et
N
H

(DHQD)2PHAL

bis(dihydroquinidino)phthalazine

H

N
N N

O

O

H
OMe

N

N

O

DIAD

diisopropyl azodicarboxylate

N
O

O
N
O
O

DIB
(BAIB or PIDA)

(diacetoxyiodo)benzene

O
O

I
O

xxiv

H

MeO

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Abbreviation

Chemical Name

DIBAL (DIBAH)
DIBAL-H

diisobutylaluminum hydride

DIC

diisopropyl carbodiimide

diop

Chemical Structure
H
Al

N

4,5-bis-[(diphenylphosphanyl)methyl]-2,2-dimethyl[1,3]dioxolane

C

N

O

(R)

PPh2

O

(R)

PPh2

O

DIPAMP

P

1,2-bis(o-anisylphenylphosphino)ethane
P
O

DIPEA
(Hünig's base)

diisopropylethylamine

N

O

DIPT

diisopropyl tartrate

O

OH
(R) (R)

HO

O
O

O

DLP

C10H21

dilauroyl peroxide

O

O

C10H21
O

O

DMA (DMAC)

N,N-dimethylacetamide

DMAD

dimethyl acetylene dicarboxylate

DMAP

N,N-4-dimethylaminopyridine

DMB

m-dimethoxybenzene

N

O

O

O

O

N

N

O

DMDO

dimethyl dioxirane

O

O
O

DME

1,2-dimethoxyethane

xxv

O

O

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Abbreviation

Chemical Name

Chemical Structure

DMF

N,N-dimethylformamide

O

N
H

O

DMI

1,3-dimethylimidazolidin-2-one

N

N

O

DMP

Dess-Martin periodinane

O
I

OAc
AcO OAc

DMPS

Si

dimethylphenylsilyl

N

1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone
DMPU

N

(N,N-dimethyl propylene urea)
DMTSF

dimethyl(methylthio)sulfonium tetrafluoroborate

S

Me

O

Me

S

BF4

Me

DMS

dimethylsulfide

DMSO

dimethylsulfoxide

DMT

4,4’-dimethoxytrityl

S

O
S

O

O

O

DMTMM

4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4methylmorpholinium chloride

N
O

N
N

N

O

Cl

DMTr

4,4’-dimethyltrityl

DMTST

(dimethylthio)methylsulfonium
trifluoromethanesulfonate

S

DNA

deoxyribonucleic acid

xxvi

S

O F
O S

S

O F

NA

F

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Abbreviation

Chemical Name

DPA (DIPA)

diisopropylamine

Chemical Structure
N
H

DPBP

2,2'-bis(diphenylphosphino)biphenyl

(S)

Ph2P PPh2

O

DPDC

diisopropyl peroxydicarbonate

O
O

O
O
O

NN+

DPDM

diphenyl diazomethane

H2N

DPEDA

NH2
(R) (R)

1,2-diamino-1,2-diphenylethane

Ph

DPIBF

diphenylisobenzofuran

O
Ph

DPPA

diphenylphosphoryl azide (diphenylphosphorazidate)

O
O

Dppb (ddpb)

1,4-bis(diphenylphosphino)butane

P

O
N N+ N-

Ph2P
PPh2

dppe

1,2-bis(diphenylphosphino)ethane

dppf

1,1'-bis(diphenylphosphino)ferrocene

PPh2
Ph2P

PPh2
Fe
PPh2

dppm

bis(diphenylphosphino)methane

dppp

1,3-bis(diphenylphosphino)propane

DPS
(also TBDPS or
BPS)

t-butyldiphenylsilyl

Ph2P

PPh2

Ph2P

PPh2

Si

xxvii

TABLE OF CONTENTS

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Abbreviation

Chemical Name

DPTC

O,O’-di(2’-pyridyl)thiocarbonate

dr

diastereomeric ratio

DTBAD (DBAD)

di-tert-butyl azodicarboxylate

Chemical Structure
S
N

O

O

N

NA

O
N
O

O
N
O

DTBB

4,4’-di-tert-butylbiphenyl

DTBP

2,6-di-tert-butylpyridine

DTBMP

2,6-di-tert-butyl-4-methylpyridine

N

N

OH

DTE

1,4-dithioerythritol

SH
SH

DVS

OH

Me

1,3-divinyl-1,1,3,3-tetramethyldisiloxane

O

Si
Me

+

E
E2
ED

electrophile (denotes any electrophile in general)
bimolecular elimination
effective dosage

EDA

ethyl diazoacetate

Me
Si
Me

NA
NA
NA
O
N+

O

EDDA

ethylenediamine diacetate

OAc
NH3

H3N
OAc

EDC (EDAC)

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
(ethyldimethylaminopropylcarbodiimide)
N

EDCI

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
hydrochloride

N

C

C

N-

N

N

N

NH

Cl

PO3H2

EDCP

2,3-bis-phosphonopentanedioic acid
(ethylene dicarboxylic 2,3-diphosphonic acid)

EDG

electron-donating group

EDTA

ethylenediamine tetraacetic acid

HOOC

COOH
PO3H2

NA
HOOC

HOOC
N
N
COOH

xxviii

COOH

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Abbreviation

Chemical Name

Chemical Structure

ee

enantiomeric excess
ethoxyethyl

NA
O

EE

NA

Ei

intramolecular syn elimination

en

ethylenediamine

EOM

ethoxymethyl

O

ESR

electron spin resonance (spectroscopy)

NA

Et

ethyl

ETSA

ethyl trimethylsilylacetate

H2N

NH2

O
Si

O

EVE

ethyl vinyl ether

O

EWG

electron-withdrawing group

NA

Fc

ferrocenyl

Fe

H2O3POH2C

FDP

fructose-1,6-diphosphate

H

O
HO

HO

H

OH
CH2OPO3H2

H

F

FDPP

pentafluorophenyl diphenylphosphinate

F

F

O

F

Ph P O F
Ph

Fl

fluorenyl

FMO

frontier molecular orbital (theory)

NA
O
O

Fmoc

9-fluorenylmethoxycarbonyl

F
F

fod

6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5octanedione

F

F F

F O

O

F

NA

fp
FSM

flash point
Mesoporous silica

FTT

1-fluoro-2,4,6-trimethylpyridinium triflate

NA

O F
N FO S
O F

xxix

F

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Abbreviation

Chemical Name

Chemical Structure

FVP
GEBC
h
hν

flash vacuum pyrolysis
gel entrapped base catalyst
hours (length of reaction time)
irradiation with light

NA
NA
NA
NA
PF6

HATU

Het

O-(7-azabenzotriazol-1-yl)-N,N,N’,N’tetramethyluronium hexafluorophosphate

N
O+

N
N

N
N N

NA

heterocycle
O

hfacac

hexafluoroacetylacetone

F3 C

CF3

F F

F

HFIP

O

1,1,1,3,3,3-hexafluoro-2-propanol
(hexafluoroisopropanol)

F

F

F
OH

HO

HGK

4-hydroxy-2-ketoglutarate

O
O
O O

Hgmm
HLE

millimeter of mercury (760 Hgmm = 1 atm = 760 Torr)
horse liver esterase

Hmb

2-hydroxy-4-methoxybenzyl

HMDS

1,1,1,3,3,3-hexamethyldisilazane

HMPA

hexamethylphosphoric acid triamide
(hexamethylphosphoramide)

O

NA
NA

O

OH

Si

H
N

Si

N
N P N
O

N

HMPT

hexamethylphosphorous triamide

N

P

N

N

HOAt

N

1-hydroxy-7-azabenzotriazole

N

N

OH

N

HOBt (HOBT)

N

1-hydroxybenzotriazole

N
OH

HOMO

highest occupied molecular orbital

HOSu

N-hydroxysuccinimide

HPLC
HWE
i

high-pressure liquid chromatography
Horner-Wadsworth-Emmons
iso
xxx

NA

OH
O

N

NA
NA
NA

O

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
O

IBA

I

2-iodosobenzoic acid

O
HO

O

IBX

o-iodoxybenzoic acid

O
I
HO

IDCP

bis(2,4,6-collidine)iodonium perchlorate

N

O

I+ N

ClO4-

HN

Imid (Im)

imidazole

INOC

intramolecular nitrile oxide cycloaddition

IPA

isopropyl alcohol

Ipc

isopinocamphenyl

IR
K-10

infrared spectroscopy
a type of Montmorillonite clay

KDA

potassium diisopropylamide

KHMDS

potassium bis(trimethylsilyl)amide

KSF
L

a type of Montmorillonite clay
ligand

L.R.

Lawesson’s reagent (2,4-bis-(4-methoxyphenyl)[1,3,2,4]dithiadiphosphetane 2,4-dithion)

N

NA

HO

H

NA
NA

K

N

K
N

Si

Si

NA
NA
S
S P
MeO

OMe

P S
S

NA

LA
LAB

Lewis acid
lithium amidotrihydroborate

LAH

lithium aluminum hydride

LiAlH4

LD50

dose that is lethal to 50% of the test subjects (cells,
animals, humans etc.)

NA

LDA

lithium diisopropylamide

LiH2NBH3

N

LDBB

lithium 4,4’-t-butylbiphenylide

xxxi

Li

Li

TABLE OF CONTENTS

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Abbreviation

Chemical Name

Chemical Structure

LDE

lithium diethylamide

LDPE

lithium perchlorate-diethyl etherate

LHMDS
(LiHMDS)

lithium bis(trimethylsilyl)amide

LICA

lithium isopropylcyclohexylamide

Li

N

LiClO4 - Et2O

Li
N

Si

Si

N
Li

LICKOR (super
base)
liq.

butyllithium-potassium tert-butoxide

BuLi - KOt-Bu

liquid

NA

LiTMP
(LTMP)

lithium 2,2,6,6-tetramethylpiperidide

LPT

lithium pyrrolidotrihydroborate
(lithium pyrrolidide-borane)

L-selectride

lithium tri-sec-butylborohydride

LTA

lead tetraacetate

Pb(OAc)4

LUMO

lowest unoccupied molecular orbital

NA

lut

2,6-lutidine

m

meta

MA

maleic anhydride

MAD

Li

N

Li(CH 2)4NBH3

BH

Li

N

NA

O

methyl aluminum bis(2,6-di-t-butyl-4methylphenoxide)

O

O

O

AlMe

2

MAT

methyl aluminum bis(2,4,6-tri-t-butylphenoxide)

O

AlMe
2

xxxii

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
S

MBT

2-mercaptobenzothiazole

HS
N

COOOH

m-CPBA

meta chloroperbenzoic acid
Cl

CH3

Me

methyl

MEM

(2-methoxyethoxy)methyl

O

O

O

MEPY

methyl 2-pyrrolidone-5(S)-carboxylate

Mes

mesityl

H
N

O

O

HO

mesal

N-methylsalicylaldimine
N

MIC

methyl isocyanate

O C N

O
O

MMPP
(MMPT)

magnesium monoperoxyphthalate

Mg2+ O
O
O

O

MOM

methoxymethyl

MoOPH
mp
MPa

oxodiperoxomolybdenum(pyridine)(hexamethylphosphoric triamide)
melting point
6
megapascal = 10 Pa = 10 atm (pressure)

NA
NA

O

MPD
(NMP)

N-methyl-2-pyrrolidinone

MPM

methoxy(phenylthio)methyl

MPM
(PMB)

p-methoxybenzyl

N

O
S

O

xxxiii

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
Cl

MPPC

NH

O Cr O

N-methyl piperidinium chlorochromate

O
O
S CH3

Ms

mesyl (methanesulfonyl)

MS
MS

mass spectrometry
molecular sieves

NA

MSA

methanesulfonic acid

HO S CH3

MSH

o-mesitylenesulfonyl hydroxylamine

O

NA
O
O
H
N

HO

O
S

O

O
F

MSTFA

N-methyl-N-(trimethylsilyl) trifluoroacetamide

Si

N

F

F
O

MTAD

O

N-methyltriazolinedione

N
N N

MTEE
(MTBE)

methyl t-butyl ether

MTM

methylthiomethyl

MTO

methyltrioxorhenium

O

S

O
O Re CH3
O
Me

Mtr

Me

O

(4-methoxy-2,3,6-trimethylphenyl)sulfonyl

S

OMe

O
Me

MVK

methyl vinyl ketone
O

mw
n

NA

microwave
normal (e.g. unbranched alkyl chain)

NA
H O

H

NH2
N

O

O
NH2

NADPH

nicotinamide adenine dinucleotide phosphate

OH OH
O

O

P O P O
OH

OH

N

N
N

N
O

O
OH O P OH
OH

xxxiv

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
Na

NaHMDS

sodium bis(trimethylsilyl)amide

Naph
(Np)

naphthyl

N

Si

Si

O

NBA

N-bromoacetamide

NBD
(nbd)

norbornadiene

Br

N
H

O

NBS

N-bromosuccinimide

N Br
O
O

NCS

N Cl

N-chlorosuccinimide

O

Nf

nonafluorobutanesulfonyl

O

F

F

O

F

F

S
F

F

F

F

F

O

NHPI

N-hydroxyphthalimide

N OH
O
I
N

O

NIS

N-iodosuccinimide

NMM

N-methylmorpholine

NMO

N-methylmorpholine oxide

O

N

O

O

N
O

O

NMP

N-methyl-2-pyrrolidinone

NMR

nuclear magnetic resonance

NORPHOS

bis(diphenylphosphino)bicyclo[2.2.1]-hept-5-ene

N

NA

Ph2P

PPh2

O

Nos

4-nitrobenzenesulfonyl

S
O

xxxv

O
N
O

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
O

NPM

N-phenylmaleimide

N
O

NA

NR

no reaction

Ns

2-nitrobenzenesulfonyl

O
O N
O
S
O

NSAID
Nuc
o

non steroidal anti-inflammatory drug
nucleophile (general)
ortho

NA

Oxone

potassium peroxymonosulfate

KHSO5

p

para

NA

NA
NA

R

PAP

R
N R
N

P
N

2,8,9-trialkyl-2,5,8,9-tetraaza1-phospha-bicyclo[3.3.3]undecane

N

PBP

N

pyridinium bromide perbromide

Br3

H

O

PCC

pyridinium chlorochromate

PDC

pyridinium dichromate

PEG

polyethylene glycol

N
H

N
H

Cl

O
Cr
O

O
O
O
Cr
Cr
O
O
O O

NA
Ph

Pf

9-phenylfluorenyl

pfb

perfluorobutyrate

F
F

Ph

phenyl

PHAL

phthalazine

F O

F
O
F F

F

N
N

phen

9,10-phenanthroline
N N

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N
H

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
O
C

Phth

phthaloyl
C
O

pic

2-pyridinecarboxylate

O
O

N

O

PIDA
(BAIB or DIB)

phenyliodonium diacetate

O
O

I
O

O

PIFA

F3C

phenyliodonium bis(trifluoroacetate)

O
O

I
O

CF3

Piv

pivaloyl

PLE

pig liver esterase

PMB
(MPM)

p-methoxybenzyl

PMP

4-methoxyphenyl

PMP

1,2,2,6,6-pentamethylpiperidine

O

NA

O

O

Me

Me
N

Me

Me

Me

PNB

O

p-nitrobenzyl

N
O

O

PNZ

p-nitrobenzyloxycarbonyl

O

O
N

O

PPA

polyphosphoric acid

PPI

2-phenyl-2-(2-pyridyl)-2H-imidazole

NA

N
N
N

PPL

pig pancreatic lipase

PPO

4-(3-phenylpropyl)pyridine-N-oxide

PPSE

polyphosphoric acid trimethylsilyl ester

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NA

O N

Ph

NA

TABLE OF CONTENTS

Abbreviation

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Chemical Name

Chemical Structure
O

PPTS

S O

pyridinium p-toluenesulfonate

Pr

propyl

psi

pounds per square inch

N
H

O

NA
N N

PT

1-phenyl-1H-tetrazol-yl

N N
Ph

NA

P.T.

proton transfer

PTAB

phenyltrimethylammonium perbromide

PTC

Phase transfer catalyst

PTMSE

(2-phenyl-2-trimethylsilyl)ethyl

PTSA
(or TsOH)

p-toluenesulfonic acid

PVP

poly(4-vinylpyridine)

Py
(pyr)
r.t.
rac

pyridine

N

Br3

NA

Si

HO3S

CH3

NA

N

NA

room temperature
racemic

NA
NH2
N

RAMP

(R)-1-amino-2-(methoxymethyl)pyrrolidine

RaNi

Raney nickel

NA

RB
RCAM
RCM
Rds (or RDS)

Rose Bengal
ring-closing alkyne metathesis
ring-closing metathesis
rate-determining step

See Rose bengal

Red-Al

sodium bis(2-methoxyethoxy) aluminum hydride

(R)

O

NA
NA
NA

O

O
O
O Al H
H

H
O Me
O
O H
O H

Rham

rhamnosyl

Rf

perfluoroalkyl group

CnF2n+1

Rf

retention factor in chromatography

NA

ROM

ring-opening metathesis

NA

ROMP

ring-opening metathesis polymerization

NA

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Na

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
I

I

O

Rose Bengal
(RB)

2,4,5,7-tetraiodo-3',4',5',6'-tetrachlorofluorescein
disodium salt

O

O

I

I
Cl

2 Na

COO

(a photosensitizer)
Cl

Cl
Cl

s

seconds (length of reaction time)

S,S,-chiraphos

(S,S)-2,3-bis(diphenylphosphino)butane

NA
PPh2
(S)

(S)

PPh2

Salen

N,N’-ethylenebis(salicylideneiminato)
bis(salicylidene)ethylenediamine

N

N

OH

salophen

N

o-phenylenebis(salicylideneiminato)

N

OH

SAMP

(S)-1-amino-2-(methoxymethyl)pyrrolidine

HO

HO

NH2
N
O

SC CO2

supercritical carbon-dioxide

SDS

sodium dodecylsulfate

NA
O Na
O S O
O

NA

sec

secondary

SEM

2-(trimethylsilyl)ethoxymethyl

SES

2-[(trimethylsilyl)ethyl]sulfonyl

Si

O

O

Si

S
O

SET

single electron transfer

Sia

1,2-dimethylpropyl (secondary isoamyl)

SPB

sodium perborate

NA

Na BO3

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TABLE OF CONTENTS

Abbreviation
TADDOL

SEARCH TEXT

Chemical Name
1

Chemical Structure
H

1

2,2-dimethyl-α,α,α , α -tetraaryl-1,3-dioxolane-4,5dimethanol

O

OH
Ar
Ar
Ar

(R)
(R)

O
H

Ar
OH

NEt2

TASF

tris(diethylamino)sulfonium difluorotrimethylsilicate

Et2N

S

SiMe3F2

NEt2

TBAB

tetra-n-butylammonium bromide
N

Br

TBAF

tetra-n-butylammonium fluoride

Bu4N F

TBAI

tetra-n-butylammonium iodide

Bu4N I

Br

TBCO

tetrabromocyclohexadienone

Br
O
Br
Br

TBDMS
(TBS)

t-butyldimethylsilyl

TBDPS
(BPS)

t-butyldiphenylsilyl

TBH

tert-butyl hypochlorite

O

TBHP

tert-butyl hydroperoxide

O

TBP

tributylphosphine

Si

Si

Cl

OH

P

N N

TBT

N N

1-tert-butyl-1H-tetrazol-5-yl

t-Bu

TBTH

tributyltin hydride

TBTSP

t-butyl trimethylsilyl peroxide

H
Sn

xl

Si

O

O

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
O

TCCA

trichloroisocyanuric acid

Cl
N

Cl

N

O
N

O

Cl

S

TCDI

thiocarbonyl diimidazole

N

N

N

TCNE

TCNQ

N

N

N

N

N

tetracyanoethylene

NC

CN

NC

CN

7,7,8,8-tetracyano-para-quinodimethane

Si

TDS

dimethyl thexylsilyl

TEA

triethylamine

TEBACl

benzyl trimethylammonium chloride

TEMPO

2,2,6,6-tetramethyl-1-piperidinyloxy free radical

N

Cl
N

N
O•

Teoc

2-(trimethylsilyl)ethoxycarbonyl
O

Si

O

O

TEP

triethylphosphite

TES

triethylsilyl

P O
O

Si

F

trifluoromethanesulfonyl

F

TFA

trifluoroacetic acid

F

Tfa

trifluoroacetamide

F

Tf

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O
S

F

O

F

OH

F

O

F

NH2

F

O

TABLE OF CONTENTS

Abbreviation

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Chemical Name

Chemical Structure
O

O

F

TFAA

TFE

trifluoroacetic anhydride

F
O

F

F

F

F

2,2,2-trifluoroethanol

OH

F

TFMSA

trifluoromethanesulfonic acid
(triflic acid)

TFP

tris(2-furyl)phosphine

F
F O

F

S OH
F O

O
P

O

O

S

Th

2-thienyl

thexyl

1,1,2-trimethylpropyl

THF

tetrahydrofuran

THP

2-tetrahydropyranyl

TIPB

1,3,5-triisopropylbenzene

TIPS

triisopropylsilyl

TMAO (TMANO)

trimethylamine N-oxide

TMEDA

N,N,N',N'-tetramethylethylenediamine

TMG

1,1,3,3-tetramethylguanidine

O

O

Si

N+ O-

N

N

N

N
NH

TMGA

tetramethylguanidinium azide

N

N
NH2
N3

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F

TABLE OF CONTENTS

Abbreviation

SEARCH TEXT

Chemical Name

Chemical Structure
O

Tmob

2,4,6-trimethoxybenzyl

O
O

TMP

2,2,6,6-tetramethylpiperidine

TMS

trimethylsilyl

TMSA

trimethylsilyl azide

TMSEE

(trimethylsilyl)ethynyl ether

N
H

Si

Si

N

N+

N-

Si

Si
O

TMU

N

tetramethylurea

N
O

-

O

-

O

N+

O

O
N+
O
N+ O
O
O

TNM

tetranitromethane

Tol

p-tolyl

tolbinap

2,2'-bis(di-p-tolylphosphino)-1,1'-binaphthyl

+

N

2

P
P

2

O
N

TPAP

tetra-n-propylammonium perruthenate

TPP

triphenylphosphine

O Ru O
O

P

Ph

NH

TPP

5,10,15,20-tetraphenylporphyrin

N
Ph

Ph
N

HN

Ph

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Abbreviation

Chemical Name

Chemical Structure

TPS

triphenylsilyl

Si

Tr

trityl (triphenylmethyl)

C

Trisyl

2,4,6-triisopropylbenzenesulfonyl

O
S
O

Troc

2,2,2-trichloroethoxycarbonyl

Cl

Cl

O

Cl

O

TS

transition state (or transition structure)

Ts (Tos)

p-toluenesulfonyl

NA
O
S
O

TSE (TMSE)

2-(trimethylsilyl)ethyl

TTBP

2,4,5-tri-tert-butylpyrimidine

Si

N
N

TTMSS

tris(trimethylsilyl)silane

Si
Si SiH
Si

TTN

thallium(III)-trinitrate

Tl(NO3)3

UHP

urea-hydrogen peroxide complex

H2 N

NH2
H2O2
O

O

Vitride
(Red-Al)

sodium bis(2-methoxyethoxy)aluminum hydride

O
O
O Al H
Na

H

wk

weeks (length of reaction time)

Z (Cbz)

benzyloxycarbonyl

NA
O
O

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VI. LIST OF NAMED ORGANIC REACTIONS

Acetoacetic Ester Synthesis....................................................................................................................................2
Acyloin Condensation .............................................................................................................................................4
Alder (Ene) Reaction (Hydro-Allyl Addition) ............................................................................................................6
Aldol Reaction .........................................................................................................................................................8
Alkene (Olefin) Metathesis ....................................................................................................................................10
Alkyne Metathesis .................................................................................................................................................12
Amadori Reaction/Rearrangement........................................................................................................................14
Arbuzov Reaction (Michaelis-Arbuzov Reaction) ..................................................................................................16
Arndt-Eistert Homologation/Synthesis...................................................................................................................18
Aza-Claisen Rearrangement (3-Aza-Cope Rearrangement).................................................................................20
Aza-Cope Rearrangement ....................................................................................................................................22
Aza-Wittig Reaction...............................................................................................................................................24
Aza-[2,3]-Wittig Rearrangement............................................................................................................................26
Baeyer-Villiger Oxidation/Rearrangement .............................................................................................................28
Baker-Venkataraman Rearrangement ..................................................................................................................30
Baldwin’s Rules/Guidelines for Ring-Closing Reactions .......................................................................................32
Balz-Schiemann Reaction (Schiemann Reaction).................................................................................................34
Bamford-Stevens-Shapiro Olefination...................................................................................................................36
Barbier Coupling Reaction ....................................................................................................................................38
Bartoli Indole synthesis .........................................................................................................................................40
Barton Nitrite Ester Reaction.................................................................................................................................42
Barton Radical Decarboxylation Reaction.............................................................................................................44
Barton-McCombie Radical Deoxygenation Reaction ............................................................................................46
Baylis-Hillman Reaction ........................................................................................................................................48
Beckmann Rearrangement ...................................................................................................................................50
Benzilic Acid Rearrangement ................................................................................................................................52
Benzoin and Retro-Benzoin Condensation ...........................................................................................................54
Bergman Cycloaromatization Reaction .................................................................................................................56
Biginelli Reaction...................................................................................................................................................58
Birch Reduction.....................................................................................................................................................60
Bischler-Napieralski Isoquinoline Synthesis ..........................................................................................................62

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Brook Rearrangement...........................................................................................................................................64
Brown Hydroboration Reaction .............................................................................................................................66
Buchner Method of Ring Expansion (Buchner Reaction) ......................................................................................68
Buchwald-Hartwig Cross-Coupling .......................................................................................................................70
Burgess Dehydration Reaction..............................................................................................................................72
Cannizzaro Reaction.............................................................................................................................................74
Carroll Rearrangement (Kimel-Cope Rearrangement)..........................................................................................76
Castro-Stephens Coupling ....................................................................................................................................78
Chichibabin Amination Reaction (Chichibabin Reaction) ......................................................................................80
Chugaev Elimination Reaction (Xanthate Ester Pyrolysis)....................................................................................82
Ciamician-Dennstedt Rearrangement ...................................................................................................................84
Claisen Condensation/Claisen Reaction ...............................................................................................................86
Claisen Rearrangement ........................................................................................................................................88
Claisen-Ireland Rearrangement ............................................................................................................................90
Clemmensen Reduction........................................................................................................................................92
Combes Quinoline Synthesis ................................................................................................................................94
Cope Elimination / Cope Reaction ........................................................................................................................96
Cope Rearrangement............................................................................................................................................98
Corey-Bakshi-Shibata Reduction (CBS Reduction) ............................................................................................100
Corey-Chaykovsky Epoxidation and Cyclopropanation.......................................................................................102
Corey-Fuchs Alkyne Synthesis ...........................................................................................................................104
Corey-Kim Oxidation ...........................................................................................................................................106
Corey-Nicolaou Macrolactonization.....................................................................................................................108
Corey-Winter Olefination.....................................................................................................................................110
Cornforth Rearrangement ...................................................................................................................................112
Criegee Oxidation ...............................................................................................................................................114
Curtius Rearrangement.......................................................................................................................................116
Dakin Oxidation...................................................................................................................................................118
Dakin-West Reaction ..........................................................................................................................................120
Danheiser Benzannulation ..................................................................................................................................122
Danheiser Cyclopentene Annulation ...................................................................................................................124
Danishefsky’s Diene Cycloaddition .....................................................................................................................126
Darzens Glycidic Ester Condensation.................................................................................................................128
Davis' Oxaziridine Oxidations..............................................................................................................................130

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De Mayo Cycloaddition (Enone-Alkene [2+2] Photocycloaddition) .....................................................................132
Demjanov Rearrangement and Tiffeneau-Demjanov Rearrangement ................................................................134
Dess-Martin Oxidation.........................................................................................................................................136
Dieckmann Condensation ...................................................................................................................................138
Diels-Alder Cycloaddition ....................................................................................................................................140
Dienone-Phenol Rearrangement.........................................................................................................................142
Dimroth Rearrangement......................................................................................................................................144
Doering-LaFlamme Allene Synthesis ..................................................................................................................146
Dötz Benzannulation Reaction ............................................................................................................................148
Enders SAMP/RAMP Hydrazone Alkylation........................................................................................................150
Enyne Metathesis................................................................................................................................................152
Eschenmoser Methenylation ...............................................................................................................................154
Eschenmoser-Claisen Rearrangement ...............................................................................................................156
Eschenmoser-Tanabe Fragmentation.................................................................................................................158
Eschweiler-Clarke Methylation (Reductive Alkylation) ........................................................................................160
Evans Aldol Reaction ..........................................................................................................................................162
Favorskii and Homo-Favorskii Rearrangement ...................................................................................................164
Feist-Bénary Furan Synthesis .............................................................................................................................166
Ferrier Reaction/Rearrangement.........................................................................................................................168
Finkelstein Reaction............................................................................................................................................170
Fischer Indole Synthesis .....................................................................................................................................172
Fleming-Tamao Oxidation...................................................................................................................................174
Friedel-Crafts Acylation.......................................................................................................................................176
Friedel-Crafts Alkylation ......................................................................................................................................178
Fries-, Photo-Fries, and Anionic Ortho-Fries Rearrangement.............................................................................180
Gabriel Synthesis ................................................................................................................................................182
Gattermann and Gattermann-Koch Formylation .................................................................................................184
Glaser Coupling ..................................................................................................................................................186
Grignard Reaction ...............................................................................................................................................188
Grob Fragmentation ............................................................................................................................................190
Hajos-Parrish Reaction .......................................................................................................................................192
Hantzsch Dihydropyridine Synthesis...................................................................................................................194
Heck Reaction.....................................................................................................................................................196
Heine Reaction....................................................................................................................................................198

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Hell-Volhard-Zelinsky Reaction ...........................................................................................................................200
Henry Reaction ...................................................................................................................................................202
Hetero Diels-Alder Cycloaddition (HDA) .............................................................................................................204
Hofmann Elimination ...........................................................................................................................................206
Hofmann-Löffler-Freytag Reaction (Remote Functionalization) ..........................................................................208
Hofmann Rearrangement....................................................................................................................................210
Horner-Wadsworth-Emmons Olefination.............................................................................................................212
Horner-Wadsworth-Emmons Olefination – Still-Gennari Modification .................................................................214
Houben-Hoesch Reaction/Synthesis...................................................................................................................216
Hunsdiecker Reaction .........................................................................................................................................218
Jacobsen Hydrolytic Kinetic Resolution ..............................................................................................................220
Jacobsen-Katsuki Epoxidation ............................................................................................................................222
Japp-Klingemann Reaction .................................................................................................................................224
Johnson-Claisen Rearrangement........................................................................................................................226
Jones Oxidation/Oxidation of Alcohols by Chromium Reagents .........................................................................228
Julia-Lythgoe Olefination.....................................................................................................................................230
Kagan-Molander Samarium Diiodide-Mediated Coupling ...................................................................................232
Kahne Glycosidation ...........................................................................................................................................234
Keck Asymmetric Allylation .................................................................................................................................236
Keck Macrolactonization .....................................................................................................................................238
Keck Radical Allylation........................................................................................................................................240
Knoevenagel Condensation ................................................................................................................................242
Knorr Pyrrole Synthesis ......................................................................................................................................244
Koenigs-Knorr Glycosidation...............................................................................................................................246
Kolbe-Schmitt Reaction.......................................................................................................................................248
Kornblum Oxidation.............................................................................................................................................250
Krapcho Dealkoxycarbonylation (Krapcho reaction) ...........................................................................................252
Kröhnke Pyridine Synthesis ................................................................................................................................254
Kulinkovich Reaction...........................................................................................................................................256
Kumada Cross-Coupling .....................................................................................................................................258
Larock Indole Synthesis ......................................................................................................................................260
Ley Oxidation ......................................................................................................................................................262
Lieben Haloform Reaction...................................................................................................................................264
Lossen Rearrangement.......................................................................................................................................266

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Luche Reduction .................................................................................................................................................268
Madelung Indole Synthesis .................................................................................................................................270
Malonic Ester Synthesis......................................................................................................................................272
Mannich Reaction ...............................................................................................................................................274
McMurry Coupling ...............................................................................................................................................276
Meerwein Arylation..............................................................................................................................................278
Meerwein-Ponndorf-Verley Reduction ................................................................................................................280
Meisenheimer Rearrangement............................................................................................................................282
Meyer-Schuster and Rupe Rearrangement ........................................................................................................284
Michael Addition Reaction...................................................................................................................................286
Midland Alpine Borane Reduction .......................................................................................................................288
Minisci Reaction ..................................................................................................................................................290
Mislow-Evans Rearrangement ............................................................................................................................292
Mitsunobu Reaction ............................................................................................................................................294
Miyaura Boration .................................................................................................................................................296
Mukaiyama Aldol Reaction..................................................................................................................................298
Myers Asymmetric Alkylation ..............................................................................................................................300
Nagata Hydrocyanation.......................................................................................................................................302
Nazarov Cyclization ............................................................................................................................................304
Neber Rearrangement ........................................................................................................................................306
Nef Reaction .......................................................................................................................................................308
Negishi Cross-Coupling ......................................................................................................................................310
Nenitzescu Indole Synthesis ...............................................................................................................................312
Nicholas Reaction ...............................................................................................................................................314
Noyori Asymmetric Hydrogenation......................................................................................................................316
Nozaki-Hiyama-Kishi Reaction............................................................................................................................318
Oppenauer Oxidation ..........................................................................................................................................320
Overman Rearrangement ...................................................................................................................................322
Oxy-Cope Rearrangement and Anionic Oxy-Cope Rearrangement....................................................................324
Paal-Knorr Furan Synthesis ................................................................................................................................326
Paal-Knorr Pyrrole Synthesis ..............................................................................................................................328
Passerini Multicomponent Reaction ....................................................................................................................330
Paterno-Büchi Reaction ......................................................................................................................................332
Pauson-Khand Reaction .....................................................................................................................................334

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Payne Rearrangement ........................................................................................................................................336
Perkin Reaction...................................................................................................................................................338
Petasis Boronic Acid-Mannich Reaction .............................................................................................................340
Petasis-Ferrier Rearrangement...........................................................................................................................342
Peterson Olefination............................................................................................................................................344
Pfitzner-Moffatt Oxidation....................................................................................................................................346
Pictet-Spengler Tetrahydroisoquinoline Synthesis ..............................................................................................348
Pinacol and Semipinacol Rearrangement ...........................................................................................................350
Pinner Reaction...................................................................................................................................................352
Pinnick Oxidation ................................................................................................................................................354
Polonovski Reaction............................................................................................................................................356
Pomeranz-Fritsch Reaction.................................................................................................................................358
Prévost Reaction.................................................................................................................................................360
Prilezhaev Reaction ............................................................................................................................................362
Prins Reaction.....................................................................................................................................................364
Prins-Pinacol Rearrangement .............................................................................................................................366
Pummerer Rearrangement .................................................................................................................................368
Quasi-Favorskii Rearrangement .........................................................................................................................370
Ramberg-Bäcklund Rearrangement....................................................................................................................372
Reformatsky Reaction.........................................................................................................................................374
Regitz Diazo Transfer .........................................................................................................................................376
Reimer-Tiemann Reaction ..................................................................................................................................378
Riley Selenium Dioxide Oxidation .......................................................................................................................380
Ritter Reaction ....................................................................................................................................................382
Robinson Annulation ...........................................................................................................................................384
Roush Asymmetric Allylation...............................................................................................................................386
Rubottom Oxidation ............................................................................................................................................388
Saegusa Oxidation..............................................................................................................................................390
Sakurai Allylation.................................................................................................................................................392
Sandmeyer Reaction...........................................................................................................................................394
Schmidt Reaction ................................................................................................................................................396
Schotten-Baumann Reaction ..............................................................................................................................398
Schwartz Hydrozirconation .................................................................................................................................400
Seyferth-Gilbert Homologation ............................................................................................................................402

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Sharpless Asymmetric Aminohydroxylation ........................................................................................................404
Sharpless Asymmetric Dihydroxylation ...............................................................................................................406
Sharpless Asymmetric Epoxidation.....................................................................................................................408
Shi Asymmetric Epoxidation ...............................................................................................................................410
Simmons-Smith Cyclopropanation ......................................................................................................................412
Skraup and Doebner-Miller Quinoline Synthesis.................................................................................................414
Smiles Rearrangement .......................................................................................................................................416
Smith-Tietze Multicomponent Dithiane Linchpin Coupling ..................................................................................418
Snieckus Directed Ortho Metalation....................................................................................................................420
Sommelet-Hauser Rearrangement .....................................................................................................................422
Sonogashira Cross-Coupling ..............................................................................................................................424
Staudinger Ketene Cycloaddition ........................................................................................................................426
Staudinger Reaction............................................................................................................................................428
Stephen Aldehyde Synthesis (Stephen Reduction).............................................................................................430
Stetter Reaction ..................................................................................................................................................432
Stevens Rearrangement .....................................................................................................................................434
Stille Carbonylative Cross-Coupling....................................................................................................................436
Stille Cross-Coupling (Migita-Kosugi-Stille Coupling)..........................................................................................438
Stille-Kelly Coupling ............................................................................................................................................440
Stobbe Condensation..........................................................................................................................................442
Stork Enamine Synthesis ....................................................................................................................................444
Strecker Reaction................................................................................................................................................446
Suzuki Cross-Coupling (Suzuki-Miyaura Cross-Coupling) ..................................................................................448
Swern Oxidation..................................................................................................................................................450
Takai-Utimoto Olefination (Takai Reaction) ........................................................................................................452
Tebbe Olefination/Petasis-Tebbe Olefination......................................................................................................454
Tishchenko Reaction...........................................................................................................................................456
Tsuji-Trost Reaction/Allylation.............................................................................................................................458
Tsuji-Wilkinson Decarbonylation Reaction ..........................................................................................................460
Ugi Multicomponent Reaction .............................................................................................................................462
Ullmann Biaryl Ether and Biaryl Amine Synthesis/Condensation ........................................................................464
Ullmann Reaction/Coupling/Biaryl Synthesis ......................................................................................................466
Vilsmeier-Haack Formylation ..............................................................................................................................468
Vinylcyclopropane-Cyclopentene Rearrangement ..............................................................................................470

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von Pechman Reaction .......................................................................................................................................472
Wacker Oxidation................................................................................................................................................474
Wagner-Meerwein Rearrangement .....................................................................................................................476
Weinreb Ketone Synthesis ..................................................................................................................................478
Wharton Fragmentation ......................................................................................................................................480
Wharton Olefin Synthesis (Wharton Transposition) ............................................................................................482
Williamson Ether Synthesis.................................................................................................................................484
Wittig Reaction ....................................................................................................................................................486
Wittig Reaction - Schlosser Modification .............................................................................................................488
Wittig-[1,2]- and [2,3]-Rearrangement.................................................................................................................490
Wohl-Ziegler Bromination....................................................................................................................................492
Wolff Rearrangement ..........................................................................................................................................494
Wolff-Kishner Reduction .....................................................................................................................................496
Wurtz Coupling....................................................................................................................................................498
Yamaguchi Macrolactonization ...........................................................................................................................500

lii

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NAMED ORGANIC REACTIONS IN ALPHABETICAL ORDER

2

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ACETOACETIC ESTER SYNTHESIS
(References are on page 531)
Importance:
1-4

5-9

10-19

[Seminal Publications ; Reviews ; Modifications & Improvements

]

The preparation of ketones via the C-alkylation of esters of 3-oxobutanoic acid (acetoacetic esters) is called the
acetoacetic ester synthesis. Acetoacetic esters can be deprotonated at either the C2 or at both the C2 and C4
carbons, depending on the amount of base used. The C-H bonds on the C2 carbon atom are activated by the
electron-withdrawing effect of the two neighboring carbonyl groups. These protons are fairly acidic (pKa ~11 for C2
and pKa ~24 for C4), so the C2 position is deprotonated first in the presence of one equivalent of base (sodium
alkoxide, LDA, NaHMDS or LiHMDS, etc.). The resulting anion can be trapped with various alkylating agents. A
second alkylation at C2 is also possible with another equivalent of base and alkylating agent. When an acetoacetic
13-15,18,19
When an
ester is subjected to excess base, the corresponding dianion (extended enolate) is formed.
electrophile (e.g., alkyl halide) is added to the dianion, alkylation occurs first at the most nucleophilic (reactive) C4
position. The resulting alkylated acetoacetic ester derivatives can be subjected to two types of hydrolytic cleavage,
depending on the conditions: 1) dilute acid hydrolyzes the ester group, and the resulting β-keto acid undergoes
decarboxylation to give a ketone (mono- or disubstituted acetone derivative); 2) aqueous base induces a retroClaisen reaction to afford acids after protonation. The hydrolysis by dilute acid is most commonly used, since the
reaction mixture is not contaminated with by-products derived from ketonic scission. More recently the use of the
Krapcho decarboxylation allows neutral decarboxylation conditions.11,12 As with malonic ester, monoalkyl derivatives
of acetoacetic ester undergo a base-catalyzed coupling reaction in the presence of iodine. Hydrolysis and
decarboxylation of the coupled products produce γ-diketones. The starting acetoacetic esters are most often obtained
via the Claisen condensation of the corresponding esters, but other methods are also available for their
5,8
preparation.
O
4

3

O

O
2

O

O

acetoacetic ester

1. NaOR1 / I2

O

R
O
γ-Diketone

OR

1

O

1. H3O+
2. heat (-CO2)

O

3

R R
C2 dialkylated
acetoacetic ester

R2

OR1

1. H3O+
2. heat (-CO2)

O

O

R2

R2

C4 monoalkylated
acetoacetic ester

dianion

OR1
2

1. H3O+
2. heat (-CO2)

2. H3O+
3. heat (-CO2)

2

R2 X

O

R2

O

O

O

R3 X

R2
C2 monoalkylated
acetoacetic ester

enolate

base
(excess)

base (1 equiv)
OR1

OR1

OR1

1

O

R2 X

base (1 equiv)

R3
Disubstituted
acetone derivative

Monosubstituted
acetone derivative

R1 = 1°, 2° or 3° alkyl, aryl; R2 = 1° or 2° alkyl, allyl, benzyl; R3 = 1° or 2° alkyl, allyl, benzyl; base: NaH, NaOR1,LiHMDS, NaHMDS

Mechanism: 3,20
The first step is the deprotonation of acetoacetic ester at the C2 position with one equivalent of base. The resulting
enolate is nucleophilic and reacts with the electrophilic alkyl halide in an SN2 reaction to afford the C2 substituted
acetoacetic ester, which can be isolated. The ester is hydrolyzed by treatment with aqueous acid to the
corresponding β-keto acid, which is thermally unstable and undergoes decarboxylation via a six-membered transition
state.
Alkylation:
O
O
O

- [HBase]
OR
H

O

O

OR1

enolate

Base

R2

O

SN2

OR1

Hydrolysis:
O

O

1

-X

X

O
OR1

R2
C2 alkylated
acetoacetic ester

Decarboxylation:

O
1.H3O
OR1

R2
C2 alkylated
acetoacetic ester

2. P.T.

H
R2

R2

O

OH

O

O
OH R1

- HOR1
-H

R2

O

H
O
β-keto acid

R2

- CO2

H

tautomerization

O
H
enol

O
Ketone

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ACETOACETIC ESTER SYNTHESIS
Synthetic Applications:
In the laboratory of H. Hiemstra, the synthesis of the bicyclo[2.1.1]hexane substructure of solanoeclepin A was
undertaken utilizing the intramolecular photochemical dioxenone-alkene [2+2] cycloaddition reaction.21 The
dioxenone precursor was prepared from the commercially available tert-butyl acetoacetate using the acetoacetic
ester synthesis. When this dioxenone precursor was subjected to irradiation at 300 nm, complete conversion of the
starting material was observed after about 4h, and the expected cycloadduct was formed in acceptable yield.
O

Br

O

O

KOtBu, NaI (cat.)
O

O
O

THF, 0 °C to reflux, 16h

O

Ac2O, acetone
-10 °C to r.t.,16h

O

36% for 2 steps
O

hν
MeCN/acetone
(9:1 v/v)

O
O

O

r.t., 3.5h

OH

47% for
2 steps

Future
work

CO2H

H

HO

LiAlH4,
r.t.,THF,
10 min

O
H

O

OH
bicyclo
[2.1.1]hexane
skeleton

O HO

O

O

Solanoeclepin A

R. Neier et al. synthesized substituted 2-hydroxy-3-acetylfurans by the alkylation of tert-butylacetoacetate with an α22
haloketone, followed by treatment of the intermediate with trifluoroacetic acid. When furans are prepared from βketoesters and α-haloketones, the reaction is known as the Feist-Bénary reaction. A second alkylation of the C2
alkylated intermediate with various bromoalkanes yielded 2,2-disubstituted products, which upon treatment with TFA,
provided access to trisubstituted furans.

O
O

1. NaH (1.1 equiv), THF
30 min, 0 °C then

O

Br

2

O
O

(1.1 equiv)

t-butylacetoacetate

2

O

O

O

O

O
O
0 °C, 2h then r.t.,12h
92%

O

H

DCM/THF (10:1)
r.t., 12h

O

O

O

TFA, r.t., 1h or

O

O
2-Hydroxy-3-acetylfuran
derivative

87%

M. Nakada and co-workers developed a novel synthesis of tetrahydrofuran and tetrahydropyran derivatives by
reacting dianions of acetoacetic esters with epibromohydrin derivatives.23 The selective formation of the
tetrahydrofuran derivatives was achieved by the use of LiClO4 as an additive.

O

O

O
+
OEt

OH

H
Br

H

BnO

LiClO4 (2.0 equiv)
-60 °C to -40 °C to r.t.
5h; 82%

OBn

Me
dianion

H
Me

H O

OH

BnO
+

O

CO2Et
Me

CO2Et

Tetrahydrofuran : Tetrahydropyran = 135 : 1

A synthetic strategy was developed for the typical core structure of the Stemona alkaloids in the laboratory of C.H.
24
Heathcock. The precursor for the 1-azabicyclo[5.3.0]decane ring system was prepared via the successive double
alkylation of the dianion of ethyl acetoacetate.

EtO

O

O

1. LiI, DME, heat

O
OLi

O

O

O

OLi

i-Pr

1.3h, 0 °C
87%
O

I

EtO2C

O

Cl

2. NaOMe, MeOH
3. set pH 1
4. toluene, heat
47% overall

O

steps

H C N

O

1-Azabicyclo[5.3.0]decane
system

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ACYLOIN CONDENSATION
(References are on page 531)
Importance:
[Seminal Publications

1-4

; Reviews

5-9

10-22

; Modifications & Improvements

]

The acyloin condensation affords acyloins (α-hydroxy ketones) by treating aliphatic esters with molten, highly
dispersed sodium in hot xylene.8 The resulting disodium acyloin derivatives are acidified to liberate the corresponding
acyloins, which are valuable synthetic intermediates. Aliphatic monoesters give symmetrical compounds, while
diesters lead to cyclic acyloins. The intramolecular acyloin condensation is one of the best ways of closing rings of 10
6
members or more (up to 34 membered rings were synthesized). For the preparation of aromatic acyloins (R=Ar), the
benzoin condensation between two aromatic aldehydes is applied. The acyloin condensation is performed in an inert
atmosphere, since the acyloins and their anions are readily oxidized. For small rings (ring size: 4-6), yields are greatly
improved in the presence of TMSCl and by the use of ultrasound.11,13 The addition of TMSCl increases the scope of
this reaction by preventing base-catalyzed side reactions such as β-elimination, Claisen or Dieckmann
condensations. The resulting bis-silyloxyalkenes are either isolated or converted into acyloins by simple hydrolysis or
alcoholysis.
O

O

R

O

R'

TMSO

molten sodium metal

+
R

R'

O

TMSCl

R

xylene, reflux

H+ / H2O

OTMS

O

R

HO

R

R

H
Acyloin

bis-silyloxyalkene

Mechanism: 5,6,23
There are currently two proposed mechanisms for the acyloin ester condensation reaction. In mechanism A the
sodium reacts with the ester in a single electron transfer (SET) process to give a radical anion species, which can
dimerize to a dialkoxy dianion.5,6 Elimination of two alkoxide anions gives a diketone. Further reduction (electron
transfer from the sodium metal to the diketone) leads to a new dianion, which upon acidic work-up yields an enediol
23
that tautomerizes to an acyloin. In mechanism B an epoxide intermediate is proposed.

Mechanism A:

2

R1

OR2

R1

2 Na

OR2

R 2O
R1
O

dimerization

+

reduction

O

R1

OR2

O

O

Na

Na

Na

R1

2 H 3O

R1

reduction

- 2 OR2

R1

R1

O
diketone
OH
H

OH

O Na

2 Na

O

OR2
R1
O
Na

tautomerization

R1

R1

acidic work-up

R1

O
Acyloin

OH
enediol

O
Na

R1

Mechanism B:
O

R'
O

O
R

1

O

R'

Na

O

reduction

3

R

O

OR'

R

3

R

R'O

1

O

R

1
2

O

3

reduction

3

R

R

R

O Na
1

2

O
OR'
Na R

1

O

- NaOR'

3

R

O
diketone

O

2

2

R
O Na

OH

2 H 3O
acidic work-up

3

R

1

R

2

O

Na

Na O
R

R

OR'

OR'

epoxide intermediate

2 Na

OR'
Na

1

Na O

3

R

Na

reduction

O Na

2

2

O

2

2

R'

3

R

Na

OR'
- NaOR'

1

O

1

R

OH
enediol

tautomerization

H
R

OH
3

1

O
Acyloin

R

R

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ACYLOIN CONDENSATION
Synthetic Applications:
J. Salaün and co-workers studied the ultrasound-promoted acyloin condensation and cyclization of carboxylic
esters.13 They found that the acyloin coupling of 1,4-, 1,5-, and 1,6-diesters afforded 4-, 5- and 6-membered ring
products. The cyclization of β-chloroesters to 3-membered ring products in the presence of TMSCl, which previously
required highly dispersed sodium, was simplified and improved under sonochemical activation.

1

Me

COOEt

2

3

2

1

COOEt

1

Me

OTMS

COOMe

2

4

5

3

1

3

COOMe

2

OTMS

3

Na / TMSCl

1

2

)))), 2 h

Me

H

OTMS

OMe

Me

85%

OTMS

1

1

)))), 1.75 h

OTMS

Br
4

85%

2

OTMS

2

Na / TMSCl

1

3

3

)))), 1.75 h

5

4

3

Na / TMSCl

COOEt

2

Cl

)))), 2.5 h
80%

COOEt
4

3

Me

Na / TMSCl

OMe

Me

84%

The diterpene alkaloids of the Anopterus species, of which anopterine (R=tigloyl) is a major constituent, are
associated with a high level of antitumor activity. All of these alkaloids contain the tricyclo[3.3.21,4.0]decane
substructure. S. Sieburth et al. utilized the acyloin condensation as a key step in the short construction of this tricyclic
framework.24

7

MeO2C
H3C
6

MOMO

TMSO

H
5

7
4

2

H

Na / TMSCl

OMOM

3

CH3
CO2Me

H3C

PhMe, reflux

1

90%

1

H
HF, MeCN

OH
H3C
H

H3C

4

5

MOMO

OMOM

3

H

2

H

2 1

CH3
7

OTMS

4

3

OTMS

HO N

Future work

CH3

6

MOMO

CH3

HO

OMOM

OMOM

5

H

6

H

OTMS

OR

R = tigloyl

RO

O

H
MOMO
Anopterine

D.J. Burnell et al. synthesized bicyclic diketones by Lewis acid-promoted geminal acylation involving cyclic acyloins
tethered to an acetal. The required bis-silyloxyalkenes were prepared by using the standard acyloin condensation
conditions.25

1
2

O

H3C
9

O
8
7

CO2Et

3
6
5

CO2Et
4

TMSO

Na / TMSCl
toluene, reflux
82%

O

H3C

9

O

1

6
3

8
7

OTMS

4

5

2

1. BF3.OEt2 (2 equiv)
DCM, -78 °C
2. warm-up to r.t.
then
TFA (10 equiv)
36% for 2 steps

O
9

4

H3C

O

7

6

8
5

1
3

2

Bicyclic diketone

6

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ALDER (ENE) REACTION
(HYDRO-ALLYL ADDITION)
(References are on page 532)
Importance:
1-6

7-33

[Seminal Publications ; Reviews

; Theoretical Studies

34-44

]

In 1943, K. Alder systematically studied reactions that involved the activation of an allylic C-H bond and the allylic
transposition of the C=C bond of readily available alkenes.4-6 This reaction is known as the ene reaction. Formally it is
the addition of alkenes to double bonds (C=C or C=O), and it is one of the simplest ways to form C-C bonds. The ene
reaction of an olefin bearing an allylic hydrogen atom is called “carba-ene reaction”. For the reaction to proceed
without a catalyst, the alkene must have an electron-withdrawing (EWG) substituent. This electrophilic compound is
called the enophile. The ene reaction has a vast number of variants in terms of the enophile used.7-9,11,12,45,14-16,46,1820,24,47,27-30
Olefins are relatively unreactive as enophiles, whereas acetylenes are more enophilic. For example, under
high pressure acetylene reacts with a variety of simple alkenes to form 1,4-dienes. When the enophile is a carbonyl
compound, the ene reaction leads exclusively to the corresponding alcohol instead of the ether (carbonyl-ene
reaction). However, thiocarbonyl compounds react mainly to give allylic sulfides rather than homoallylic thiols. Schiff
bases derived from aldehydes afford homoallylic amines (aza-ene, imino-ene or hetero-ene reaction).19 Metallo-ene
reactions with Pd, Pt, and Ni-catalyzed versions have been successful in intramolecular systems. The ene reaction is
compatible with a variety of functional groups that can be appended to the ene and enophile. The ene reaction can be
highly stereoselective and by adding Lewis acids (RAlX2, Sc(OTf)3, LiClO4, etc.), less reactive enophiles can also be
used. The regioselectivity of the reaction is determined by the steric accessibility of the hydrogen. Usually primary
hydrogens are abstracted faster than secondary hydrogens and tertiary hydrogens are abstracted last.
Functionalization of the reacting components by introduction of a silyl, alkoxy, or amino group, thus changing the
steric and electronic properties, affords more control over the regioselectivity of the reaction.

+
H
ene

X

X

ene reaction

Y

H

tautomerization

Y

Z

Z

H
ene

enophile

R1
R2

Mechanism:

R1

R1
N R3 ;

O ;

X=Y :

R2

R1

R3

R2

R4

S;
R2

+

X
Y

hetero
ene reaction

X
Z

H

Y

enophile

Z: heteroatom

48-52,31

The ene reaction is mechanistically related to the better-known Diels-Alder reaction and is believed to