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Copper(I)‐Catalyzed Asymmetric Desymmetrization through Inverse‐Electron‐Demand aza‐Diels–Alder Reaction: Efficient Access to Tetrahydropyridazines Bearing a Unique α‐Chiral Silane Moiety
Author(s) -
Wei Liang,
Zhou Yu,
Song ZhiMin,
Tao HaiYan,
Lin Zhenyang,
Wang ChunJiang
Publication year - 2017
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.201700912
Subject(s) - desymmetrization , stereocenter , regioselectivity , chemistry , moiety , catalysis , silane , enantiomeric excess , stereochemistry , combinatorial chemistry , medicinal chemistry , enantioselective synthesis , organic chemistry
An unprecedented copper(I)‐catalyzed asymmetric desymmetrization of 5‐silylcyclopentadienes with in situ formed azoalkene was realized through an inverse‐electron‐demand aza‐Diels–Alder reaction (IEDDA) pathway, in which 5‐silylcyclopentadienes served as efficient enophiles. This new protocol provides a facile access to the biologically important heterocyclic tetrahydropyridazines containing a unique α‐chiral silane motif and three adjoining stereogenic centers in generally good yield (up to 92 %) with exclusive regioselectivity, high diastereoselectivity (>20:1 diastereomeric ratio), and excellent enantioselectivity (up to 98 % enantiomeric excess). DFT calculations and control experiments further confirmed the proposed reaction mechanism.