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Chem Rec. 2017 Aug;17(8):739-753. doi: 10.1002/tcr.201600124. Epub 2017 Jan 4.

Asymmetric Multicomponent Reactions Based on Trapping of Active Intermediates.

Author information

1
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.

Abstract

Metal carbenes derived from transition metal-catalyzed decomposition of diazo compounds react with nucleophiles with heteroatoms, such as alcohols and amines, to generate highly active oxonium/ammonium ylides intermediates. These intermediates can be trapped by appropriate electrophiles to provide three-component products. Based on this novel trapping process, we have developed novel multicomponent reactions (MCRs) of diazo compounds, alcohols/anilines, and electrophiles. The nucleophiles were also extended to electron-rich heterocycles (indoles and pyrroles)/arenes, in which the resulting zwitterionic intermediates were also trapped by electrophiles. By employing efficient catalysis strategy, the reactions were realized with excellent stereocontrol and wide substrate scope. In this personal account, we introduce our breakthroughs in the development of novel asymmetric MCRs via trapping of the active ylides and zwitterionic intermediates with a number of electrophiles, such as imines, aldehyde, and Michael acceptors, under asymmetric catalysis. Transition metal/chiral Lewis acid catalysis, transition metal/Br√łnsted acid catalysis, and chiral transition-metal catalysis, enable excellent stereocontrolled outcomes. The methodologies not only provide experimental evidence to support the existence of protic onium ylides intermediates/zwitterionic intermediates and the stepwise pathways of carbene-induced O-H, N-H and C-H insertions, but also offer a novel approach for the efficient construction of chiral polyfunctional molecules.

KEYWORDS:

active intermediates; asymmetric catalysis; metal carbenes; multicomponent reactions; synergistic catalysis

PMID:
28052561
DOI:
10.1002/tcr.201600124

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