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N‐Heterocyclic Carbene Catalyzed (5+1) Annulations Exploiting a Vinyl Dianion Synthon Strategy
Author(s) -
Nguyen Xuan B.,
Nakano Yuji,
Duggan Nisharnthi M.,
Scott Lydia,
Breugst Martin,
Lupton David W.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201905475
Subject(s) - synthon , cycloisomerization , annulation , chemistry , carbene , bicyclic molecule , methyl vinyl ketone , catalysis , organocatalysis , conjugate , stereochemistry , medicinal chemistry , combinatorial chemistry , enantioselective synthesis , organic chemistry , mathematical analysis , mathematics
Abstract Direct polarity inversion of conjugate acceptors provides a valuable entry to homoenolates. N‐heterocyclic carbene (NHC) catalyzed reactions, in which β‐unsubstituted conjugate acceptors undergo homoenolate formation and C−C bond formation twice, have been developed. Specifically, the all‐carbon (5+1) annulations give a range of mono‐ and bicyclic cyclohexanones (31 examples). In the first family of annulations, β‐unsubstituted acrylates tethered to a divinyl ketone undergo cycloisomerization, providing hexahydroindenes and tetralins. In the second, partially untethered substrates undergo an intermolecular (5+1) annulation involving dimerization followed by cycloisomerization. While enantioselectivity was not possible with the former, the latter proved viable, allowing cyclohexanones to be produced with high levels of enantiopurity (most >95:5 e.r.) and exclusive diastereoselectivity (>20:1 d.r.). Derivatizations and mechanistic studies are also reported.