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Synlett 2017; 28(14): 1695-1706
DOI: 10.1055/s-0036-1588453
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© Georg Thieme Verlag Stuttgart · New York

Asymmetric [3+3] Cycloaddition for Heterocycle Synthesis

Yongming Deng
Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, USA   Email: michael.doyle@utsa.edu
,
Qing-Qing Cheng
Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, USA   Email: michael.doyle@utsa.edu
,
Michael P. Doyle*
Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, USA   Email: michael.doyle@utsa.edu
› Author AffiliationsFinancial support for this research was provided by the National Institutes of Health (GM 46503) and the National Science Foundation (CHE-1212446 and CHE-1464690)
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Publication History

Received: 03 April 2017

Accepted after revision: 15 May 2017

Publication Date:
05 July 2017 (online)

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Published as part of the ISHC Conference Special Section

Abstract

Asymmetric syntheses of six-membered ring heterocycles are important research targets not only in synthetic organic chemistry but also in pharmaceuticals. The [3+3]-cycloaddition methodology is a complementary strategy to [4+2] cycloaddition for the synthesis of heterocyclic compounds. Recent progress in [3+3]-cycloaddition processes provide powerful asymmetric methodologies for the construction of six-membered ring heterocycles with one to three heteroatoms in the ring. In this account, synthetic efforts during the past five years toward the synthesis of enantioenriched six-membered ring heterocycles through asymmetric [3+3] cycloaddition are reported. Asymmetric organocatalysis uses chiral amines, thioureas, phosphoric acids, or NHC catalysis to achieve high enantiocontrol. Transition-metal catalysts used as chiral Lewis acids to activate a dipolar species is an alternative approach. The most recent advance, chiral transition-metal-catalyzed reactions of enoldiazo compounds, has contributed toward the versatile and highly selective synthesis of six-membered heterocyclic compounds.

1 Introduction

2 Asymmetric Formal [3+3]-Cycloaddition Reactions by Organo­catalysis

2.1 By Amino-Catalysis

2.2 By N-Heterocyclic Carbenes

2.3 By Bifunctional Tertiary Amine-thioureas

2.4 By Chiral Phosphoric Acids

3 Asymmetric Formal [3+3]-Cycloaddition Reactions by Transition-Metal Catalysis

3.1 Copper Catalysis

3.2 Other Transition-Metal Catalysis

4 Asymmetric [3+3]-Cycloaddition Reactions of Enoldiazo Compounds

4.1 Asymmetric [3+3]-Cycloaddition Reactions of Nitrones with Electrophilic Metallo-enolcarbene Intermediates

4.2 Dearomatization in Asymmetric [3+3]-Cycloaddition Reactions of Enoldiazoacetates

4.3 Asymmetric Stepwise [3+3]-Cycloaddition Reaction of Enoldiazoacetates with Hydrazones

5 Summary and Outlook

Key words

cycloaddition - asymmetric - heterocycles - carbene - organocatalysis - transition metal