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Qingle Zeng
Alex Adonis Nking’wa
Sulfoximines
Synthesis, Transformation and
Applications
Sulfoximines
Qingle Zeng · Alex Adonis Nking’wa
Sulfoximines
Synthesis, Transformation and Applications
Qingle Zeng
Chengdu University of Technology
Chengdu, China
Guang’an Institute of Technology
Guang’An, China
Alex Adonis Nking’wa
Morogoro, Tanzania
ISBN 978-981-96-3440-8 ISBN 978-981-96-3441-5 (eBook)
https://doi.org/10.1007/978-981-96-3441-5
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Singapore Pte Ltd. 2025
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse
of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and
transmission or information storage and retrieval, electronic adaptation, computer software, or by similar
or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specific statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book
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the editors give a warranty, expressed or implied, with respect to the material contained herein or for any
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This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd.
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Singapore
If disposing of this product, please recycle the paper.
To the scientists and researchers around the
world who dedicate their lives to the
discovery and development of innovative
compounds. This work is also for our family,
and our research group, whose support and
encouragement have made this journey
possible.
Preface
This book aims to provide a systematic and detailed account of chemistry of
sulfoximines, encompassing their history, synthesis, and applications.
The idea for this book stemmed from our years of research and teaching at
Chengdu University of Technology. We noticed a gap in the literature for a compre-
hensive text that caters t o both students and experienced researchers. Our hope is
that this book serves as a bridge, guiding readers from foundational concepts to
advanced applications in areas such as drug design and catalysis.
Writing this book has been an enriching journey, and we are grateful for the
collaborations and discussions with colleagues and students that have deepened our
understanding of this subject.
We invite you, dear reader, to explore the remarkable potential of sulfoximines,
and we hope this book will ignite your curiosity and inspire your scientific endeavors.
Chengdu, China Professor Qingle Zeng
vii
Acknowledgments This book would not have been possible without the support,
guidance, and encouragement of many individuals and organizations.
First and foremost, we would like to express our gratitude to our colleagues at
Chengdu University of Technology for their invaluable insights and collaboration
throughout this project. Special thanks go to our research group members and our
college, whose dedication and contributions have enriched this work.
We are deeply indebted to our peers in the fields of sulfoximines and organic
chemistry research, who have shared their knowledge and encouraged our exploration
of this fascinating subject.
Our heartfelt thanks also go to Chengdu University of Technology, the National
Natural Science Foundation of China, the Department of Science and Technology
of Sichuan Province, the Department of Education of the Sichuan Province, the
Chengdu Science and Technology Bureau, the State Key Laboratory of Geohazard
Prevention and Geoenvironment Protection, and other companies that supported our
research over the years, enabling us to delve deeply into this field.
Finally, we extend our love and gratitude to our family for their unwavering
patience, understanding, and support during the countless hours spent on this book.
To everyone who contributed to this endeavor, directly or indirectly, we are
profoundly grateful.
Competing Interests
The authors have no competing interests to declare that are
relevant to the content of this manuscript.
ix
Contents
1 Synthesis of Sulfoximines and Cyclic Sulfoximines ................. 1
1.1 Synthesis of Sulfoximines ................................... 1
1.1.1 Synthesis of NH-sulfoximines ........................ 3
1.1.2 Synthesis of Sulfoximines from Sulfoxides ............. 5
1.1.3 Synthesis of Sulfoximines from Thioethers ............. 10
1.1.4 Synthesis of Sulfoximines from Sulfilimines ............ 13
1.1.5 Synthesis of Chiral Sulfoximines ...................... 14
1.1.6 Summary .......................................... 18
1.2 Synthesis of Cyclic Sulfoximines ............................. 18
1.2.1 Metal Carbenoids as Coupling Partners ................ 19
1.2.2 Diazo Compounds as Carbene Precursors ............... 20
1.2.3 Ylide Active Intermediates as Carbene Precursors ....... 29
1.2.4 Metal Nitrene as Coupling Partner ..................... 35
1.2.5 Alkenes as Coupling Partner .......................... 39
1.2.6 Alkynes as Coupling Partners ......................... 41
1.2.7 Synthesis of Cyclic Sulfoximines via Intramolecular
C–H Activation ..................................... 45
1.2.8 Miscellaneous ...................................... 48
1.2.9 Summary .......................................... 49
References ..................................................... 50
2 Transformation of Sulfoximines and Cyclic Sulfoximines ........... 55
2.1 Transformation of Sulfoximines into Sulfoximine Derivatives ..... 55
2.1.1 N-Acylation of Sulfoximines ......................... 57
2.1.2 N-Arylation of NH-Sulfoximines with Halobenzenes ..... 62
2.1.3 N-Arylation of NH-Sulfoximines with Aryl Boronic
Acids ............................................. 65
2.1.4 N-Alkylation of NH-Sulfoximines ..................... 68
2.1.5 N-Alkynylation of NH-Sulfoximines ................... 71
2.1.6 Oxidative N–P Coupling of NH-Sulfoximines ........... 74
2.1.7 The N–S Coupling of Sulfoximines .................... 75
xi
xii Contents
2.1.8 C–N Bond Coupling of Imidazo[1,2-ɑ]pyridines
with NH-Sulfoximines ............................... 79
2.1.9 Cyclization Reaction of Thiadiazine 1-Oxides
and NH-Sulfoximines ............................... 80
2.1.10 Synthesis of N-methyl-2-indolyl-
and N-methyl-2-benzo[b]furyl-Substituted
Sulfoximines ....................................... 86
2.1.11 Pd(II)-Catalyzed Primary-C(sp
3
)-H Acyloxylation
of NH-Sulfoximines ................................. 88
2.1.12 Approach to Sulfonyl Azide-Directed Intermolecular
O–C–H Amidation of Arenes ......................... 91
2.1.13 Synthesis of EP3 Receptor Antagonist Analogue
from N-aroyl Sulfoximines Using Heck-Type
Reaction ........................................... 93
2.1.14 Sulfoximines Undergo Halogenation
at the β-C(sp
3
)-H Bond .............................. 95
2.1.15 Sulfoximine as Ligand for Asymmetric Catalysis ........ 97
2.2 Conversion of Sulfoximines into Other Compounds ............. 100
2.2.1 Reduction to Thioethers .............................. 100
2.2.2 Oxidation to Sulfoxides .............................. 100
2.2.3 Cleavage to Amines ................................. 100
2.2.4 N-Acylation ........................................ 101
2.2.5 N-Alkylation ....................................... 101
2.2.6 The Formation of N-Heterocycles ..................... 101
2.2.7 Transformation into Sulfinamides ..................... 101
2.2.8 Formation of Nitriles ................................ 101
2.2.9 N–Sulfonyl Imine Formation ......................... 102
2.2.10 Cleavage of S=O and S=N Bonds ..................... 102
2.2.11 Conversion of Sulfoximines to Sulfoxides .............. 104
2.2.12 Conversion of Sulfoximines to Thioethers .............. 107
2.2.13 Summary .......................................... 109
References ..................................................... 109
3 Application of Sulfoximines and Cyclic Sulfoximines ............... 113
3.1 Application of Sulfoximines ................................. 113
3.1.1 In Drugs ........................................... 113
3.1.2 Catalysis and Materials Science ....................... 115
3.1.3 In Biology Studies .................................. 115
3.2 Application of Cyclic Sulfoximines ........................... 117
3.2.1 Pharmacological Medicines .......................... 117
3.2.2 Catalysts ........................................... 117
3.2.3 Treatments and Scientific Researches .................. 118
References ..................................................... 118
4 Conclusions and Outlook ....................................... 121
Chapter 1
Synthesis of Sulfoximines and Cyclic
Sulfoximines
1.1 Synthesis of Sulfoximines
Sulfoximines are organic compounds containing a sulfinyl group (S=O) and a
nitrogen atom. They are also known for being stable and reactive, which makes
them great building blocks in the field of organic synthesis. Sulfoximines are an
interesting group of compounds that have become very important in organic chem-
istry and medicinal science. Sulfoximines are interesting to both researchers and
chemists because they are aza-analogues of sulfones. They also respond in a number
of different ways. Sulfoximines are examined in terms of their synthesis, structural
properties, uses, and growing significance in modern research, providing a compre-
hensive overview. Sulfoximines, an interesting new group of drugs, were discov-
ered in 1949 and have been receiving significant attention ever since [
1]. There
are many important merits about sulfoximines that make them useful in the fields
of medicinal chemistry and agrochemical study. Sulfoximines have many applica-
tions in the medical field. Sulfoximines are very important in the process of finding
new drugs because they have a lot of different biological activities. Sulfoximines
are used to synthesize new compounds that combat inflammation, bacteria, and
cancer, contributing to the production of medicines. Sulfoximines have found diverse
applications in the past few decades, including as reagents [
2], chiral auxiliaries
[3], chiral ligands, organocatalysts, medicines, and agrichemicals [4–6]. Sulfox-
imines are an important part of the development of crop protection agents in the
field of agrochemicals. New pesticides have been created because of their effec-
tiveness in eliminating pests, contributing to the growth of healthy agriculture. The
main reason these materials are important for making new drugs and other useful
things is that they have unique electronic and steric features. Chemicals containing
sulfoximine exhibit various biological effects. These include Bayer (BAY1000394,
BAY1143572), AstraZeneca (AZD6738) [
7, 8], and plenty more. Furthermore, mate-
rial chemistry in the field of materials science utilizes these compounds to create
functional materials with distinctive electrical and optical properties.
1