Catalytic Cascade Reactions
All chapters are thoroughly referenced, providing quick access to important original research findings and reviews so that readers can explore individual topics in greater depth. Drawing together and analyzing published findings scattered across the literature, this book provides a single source that encapsulates our current understanding of catalytic cascade processes. Moreover, it sets the stage for the development of new catalytic cascade reactions and their applications. PENG-FEI XU, PhD, is Director of Teaching Affairs and Professor of Chemistry at Lanzhou University and Deputy Director at the State Key Laboratory of Applied Organic Chemistry. Dr. Xu also serves as an Advisory Board member for the Chinese Chemical Society. During his scientific career, he has published more than 130 papers and received numerous honors and awards, most recently the Award of New Century Excellent Talents in Universities of China and the Thieme Journal Award. WEI WANG, PhD, is Professor of Chemistry at the University of New Mexico. Dr. Wang has published more than 160 peer-reviewed papers. He has received several awards, including The Creative Award from University of New Mexico, The Chinese-American Chemistry & Chemical Biology Professors Association Distinguished Junior Faculty Award, and The American Peptide Society Bruce W. Erickson Young Investigator Award.
Catalytic Cascade Reactions
AMINE-CATALYZED CASCADE REACTIONS
AIGUO SONG AND WEI WANG
1.1 Introduction 1.2 Enamine-activated cascade reactions 1.2.1 Enamine - enamine cascades 22.214.171.124 Design of enamine - enamine cascades 126.96.36.199 Examples of enamine - enamine and enamine - enamine cyclization cascades 188.8.131.52 Enamine - enamine in three-component cascades 184.108.40.206 Enamine-activated double α-functionalization 220.127.116.11 Robinson annulations 1.2.2 Enamine - iminium cascades 18.104.22.168 Design of enamine - iminium cascades 22.214.171.124 Examples of [4 + 2] reactions with enamine - activated dienes 126.96.36.199 Inverse-electron-demand [4 + 2] reactions with enamine-activated dienophiles 188.8.131.52 Enamine - iminium - enamine cascades 1.2.3 Enamine catalysis cyclization 184.108.40.206 Design of enamine-cyclization cascade reactions 220.127.116.11 Enamine-intermolecular addition cascades 18.104.22.168 Enamine-intramolecular addition cascades 22.214.171.124 Enamine-intramolecular aldol cascades 1.3 Iminium-initiated cascade reactions 1.3.1 Design of iminium - enamine cascade reactions 1.3.2 Iminium-activated Diels - Alder reactions 1.3.3 Iminium-activated sequential [4 + 2] reactions 1.3.4 Iminium-activated [3 + 2] reactions 1.3.5 Iminium-activated sequential [3 + 2] reactions 1.3.6 Iminium-activated [2 + 1] reactions 126.96.36.199 Iminium-activated cyclopropanations 188.8.131.52 Iminium-activated epoxidations 184.108.40.206 Iminium-activated aziridinations 1.3.7 Iminium-activated multicomponent reactions 1.3.8 Iminium-activated [3 + 3] reactions 220.127.116.11 Iminium-activated all-carbon-centered [3 + 3] reactions 18.104.22.168 Iminium-activated hetero-[3 + 3] reactions 1.3.9 Other iminium-activated cascade reactions 1.4 Cycle-specific catalysis cascades 1.5 Other strategies 1.6 Summary and outlook References 1.1 INTRODUCTION
Chiral amine-mediated organocatalytic cascade reactions have become a benchmark in contemporary organic synthesis, as witnessed by a number of cascade processes developed in the past decade . The great success is attributed to two unique interconvertible activation modes, enamine  and iminium activations . Enamine catalysis has been widely applied to the α-functionalizations of aldehydes and ketones. Mechanistically, dehydration between a chiral amine and the carbonyl of an aldehyde or ketone generates an intermediate, 2 , which undergoes an enantioselective α-substitution or nucleophilic addition reaction to produce respective iminium intermediate 3 or 5 ( Scheme 1.1 ). Hydrolysis affords the products and, meanwhile, releases the chiral amine catalyst.
SCHEME 1.1 Enamine-catalyzed nucleophilic substitution (a) and addition (b) reactions.
SCHEME 1.2 Iminium catalysis.
Correspondingly, iminium catalysis involves nucleophilic addition to the β-position of an iminium species 8 derived from an α,β-unsaturated aldehyde or ketone 7 with an amine catalyst ( Scheme 1.2 ).
1.2 ENAMINE-ACTIVATED CASCADE REACTIONS
We define the cascade reactions initiated by enamine catalysis in the initial step as an enamine-activated mode, although an iminium mode might be involved in the following steps. In