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Trio Catalysis Merging Enamine, Brønsted Acid, and Metal Lewis Acid Catalysis: Asymmetric Three‐Component Aza‐Diels–Alder Reaction of Substituted Cinnamaldehydes, Cyclic Ketones, and Arylamines
Author(s) -
Deng Yongming,
Kumar Siddhartha,
Wheeler Kraig,
Wang Hong
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201406569
Subject(s) - chemistry , enamine , catalysis , lewis acids and bases , ketone , lewis acid catalysis , organic chemistry , brønsted–lowry acid–base theory , chiral lewis acid , enantioselective synthesis , yield (engineering) , organocatalysis , medicinal chemistry , materials science , metallurgy
A trio catalyst system, composed of arylamine, BINOL‐derived phosphoric acid, and Y(OTf) 3 , enables the combination of enamine catalysis with both hard metal Lewis acid catalysis and Brønsted acid catalysis for the first time. Using this catalyst system, a three‐component aza‐Diels–Alder reaction of substituted cinnamaldehyde, cyclic ketone, and arylamine is carried out with high chemo‐ and enantioselectivity, affording a series of optically active 1,4‐dihydropyridine (DHP) derivatives are obtained in 91–99 % ee and 59–84 % yield. DHPs bearing a chiral quaternary carbon center are also obtained with good enantioselectivity and moderate yield (three examples). Preliminary mechanistic investigations have also been conducted.