Steric and Stereoelectronic Effects in Organic Chemistry Veejendra K

Steric and Stereoelectronic Effects in Organic Chemistry Veejendra K. Yadav

Steric and Stereoelectronic Effects in Organic Chemistry

123 Veejendra K. Yadav Department of Chemistry Indian Institute of Technology Kanpur Kanpur, Uttar Pradesh India

ISBN 978-981-10-1138-2 ISBN 978-981-10-1139-9 (eBook) DOI 10.1007/978-981-10-1139-9

Library of Congress Control Number: 2016938380

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This Springer imprint is published by Springer Nature The registered company is Springer Science+Business Media Singapore Pte Ltd. To Arpita, Dhananjay and Dhruv with love Preface

The aim of this book is to offer a decent understanding of the principles of steric and stereoelectronic effects in organic chemistry and their consequences on product selectivity and reaction rates. This book differs from most other books of the same level. In this book, strong emphasis is placed on logical evolution of the subject in a streamlined manner to aid structured comprehension of the intricacies. This book is intended for the honors undergraduate and graduate students, and the teachers. The discussion is spread over seven chapters. Chapter 1 lays the stress on the important aspects of steric and stereoelectronic effects and their control on the conformational profile and reactivity features of the molecules. Chapter 2 describes the geometrical requirements for reactions at saturated and unsaturated carbons, and the resultant stereochemical features. Application of the said geometrical requirements to intramolecular instances results in remarkable control on diastereoselectivity. Chapter 3 deals with the facial selectivity of nucleophilic additions to acyclic and cyclic carbonyl compounds, and it explains how the steric and stereoelectronic effects control the same through elaborate discussions. The selectivity profile is explained using models such as Cram’s model, Anh–Felkin modification of Cram’s model, Houk’s transition structure and electrostatic models, Cieplak’s r ! rÃ# model, and cation coordination model. Chapter 4 comments on allylic strain and its effect on the conformational profile and related stereochemical outcomes of reactions. The high diastereoselectivity observed in the reactions of Evans enolatesis solely on account of allylic strain. The conservation of orbital symmetry rules is presented in Chap. 5. After defining the bonding and antibonding orbitals of dif- ferent types, reactions such as p2 þ p2; p4 þ p2; and electrocyclic processes have been used to demonstrate the application of the rules. Chapter 6 is an amalgamation of the conservation of orbital symmetry rules and orbital overlap effect, which serves as a very powerful tool to reliably predict the stereochemical course of pericyclic reactions. It is demonstrated by examples how the orbital overlap factor allows one of the otherwise two symmetry-controlled pathways to predominate. Chapter 7 is a must read to understand some of those control elements that did not find mention in the earlier chapters. The prominent among these elements are

vii viii Preface spiroconjugation, periselectivity, torquoselectivity, a-effect, Hammett constants, Hammond postulate, and Curtin–Hammett principle. A set of questions are pro- vided at the end to challenge the reader by allowing an evaluation of the comprehension level. The book is based mainly on the lecture notes prepared for the classes at IIT Kanpur. I am grateful to the authors of many books that I have used in preparing the notes. Important among these books are: (a) Stereoelectronic Effects in Organic Chemistry by Pierre Deslongchamps, (b) Molecular Orbitals and Organic Chemical Reactions by Ian Fleming, (c) Modern Physical Organic Chemistry by Eric V. Anslyn and Dennis A. Dougherty, (d) Mechanism and Theory in Organic Chemistry by Thomas H. Lowry and Kathleen S. Richardson, and (e) The Physical Basis of Organic Chemistry by Howard Maskill. I thank Prof. J.N. Moorthy for reading the chapters critically and suggesting changes to improve the quality of presentation. I thank Prof. M.L.N. Rao for his pleasant company and stimulating discussions over numerous coffee sessions. Last but not least, I thank Dr. Arpita Yadav, my better half, and Dhananjay and Dhruv, our sons, for bearing with me while I have been busy with drawing the structures and also for their never-ending enthusiasm and support. I would appreciate and gratefully acknowledge criticism, suggestion for improvement, and detection of errors from the readers. I thank the Publishers, Springer (India) Pvt. Ltd., for bringing out the book in the present form.

Veejendra K. Yadav Contents

1 Steric and Stereoelectronic Control of Organic Molecular Structures and Organic Reactions ...... 1 1Influence of Steric Effects on Structures ...... 1 2Influence of Stereoelectronic Effects on Reactions ...... 6 3 Evaluation of the Numerical Value of Anomeric Effect ...... 28 4Influence of Anomeric Effect on Conformational Preferences . . . . 29 5Influence of Anomeric Effect on Conformational Reactivities . . . . 35 6 Conformations of Mono and Dithioacetals ...... 40 7 Conformations of Mono and Diazaacetals...... 43 References ...... 44 2 Reactions at Saturated and Unsaturated Carbons ...... 47 References ...... 68 3 Diastereoselectivity in Organic Reactions ...... 71 1 Cram’s Model for Asymmetric Synthesis ...... 72 2 Anh–Felkin Modification of Cram’s Model for Asymmetric Synthesis ...... 72 3 Cieplak’s Model for Diastereoselectivity...... 76 4 Houk’s Transition State and Electrostatic Models for Diastereoselectivity ...... 83 5 Cation Coordination Model for Diastereoselectivity ...... 86 References ...... 100 4A(1,2) and A(1,3) Strains...... 103 1 Introduction ...... 103 2A(1,2) Strain ...... 105 3 Stereocontrol in Reactions on Account of A(1,2) Strain ...... 109 4A(1,3) Strain ...... 111 5 Stereocontrol in Reactions on Account of A(1,3) Strain ...... 113

ix x Contents

6A(1,3) Strain in Amides and Its Consequences on Diastereoselectivity ...... 122 References ...... 124 5 The Conservation of Orbital Symmetry (Woodward–Hoffmann Rules) ...... 127 1 Introduction ...... 127 2 Orbitals and Symmetry Considerations ...... 128 3 p2 + p2 Reaction ...... 131 4 Electrocyclic Ring Closure and Ring Opening Reactions ...... 139 5 Diels–Alder Reaction (p4 + p2 Reaction) ...... 144 References ...... 146 6 The Overlap Component of the Stereoelectronic Factor Vis-à-Vis the Conservation of Orbital Symmetry Rules ...... 147 1 Introduction ...... 147 2 Steric Effects in the Thermal Fragmentation of Cis-3,6-Dimethyl-3,6-Dihydropyridazine...... 149 3 Orbital Overlap Effects in the Thermal Fragmentation of Cyclopropanated and Cyclobuanated Cis-3,6-Dimethyl-3,6-Dihydropyridazine...... 149 4 Orbital Overlap Effects in [1,5] Sigmatropic Shifts...... 151 5 Difﬁculties Experienced with the [1,5] Sigmatropic Shift in Cyclobutanated Species ...... 153 References ...... 155 7 Miscellaneous ...... 157 1 Spiroconjugation ...... 157 2 Periselectivity ...... 159 3 Torquoselectivity ...... 167 4 Ambident Nucleophiles ...... 169 5 Ambident Electrophiles ...... 172 6 a-Effect ...... 182 7 Carbenes ...... 184 8 Hammett Substituent Constants ...... 187 9 Hammond Postulate...... 195 10 Curtin–Hammett Principle ...... 196 11 Diastereotopic, Homotropic, and Enantiotopic Substituents ...... 197 References ...... 200

Questions ...... 203 About the Author

Veejendra K. Yadav earned his Ph.D. under the mentorship of Dr. Sukh Dev in 1982. He has carried out his postdoctoral research at University of Calgary, Memorial University of Newfoundland, University of Ottawa, and University of Southern California over the years 1983–1990 before joining Indian Institute of Technology Kanpur (IITK) as Assistant Professor in the late 1990. Over the years, he rose through ranks and became full professor in 2001. He has taught both undergraduate and postgraduate students at IITK over the past 25 years, and has remained a popular teacher among the students throughout. His research focuses on the development of new reactions with emphasis on the construction of pharma- cophores, synthesis of biologically active molecules, and computational- cum-experimental investigation of facial selectivity. He has two international patents and 80 research papers in peer-reviewed journals to his credit. More details may be found on the link: http://home.iitk.ac.in/*vijendra.