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Carbene‐Catalyzed Enantioselective Decarboxylative Annulations to Access Dihydrobenzoxazinones and Quinolones
Author(s) -
Lee Ansoo,
Zhu Joshua L.,
Feoktistova Taisiia,
Brueckner Alexander C.,
Cheong Paul H.Y.,
Scheidt Karl A.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201900600
Subject(s) - annulation , carbene , enantioselective synthesis , chemistry , catalysis , density functional theory , transition state , combinatorial chemistry , organocatalysis , trifluoromethyl , stoichiometry , computational chemistry , stereochemistry , organic chemistry , alkyl
A direct decarboxylative strategy for the generation of aza‐ o ‐quinone methides (aza‐ o ‐QMs) by N‐heterocyclic carbene (NHC) catalysis has been discovered and explored. This process requires no stoichiometric additives in contrast with current approaches. Aza‐ o ‐QMs react with trifluoromethyl ketones through a formal [4+2] manifold to access highly enantioenriched dihydrobenzoxazin‐4‐one products, which can be converted to dihydroquinolones through an interesting stereoretentive aza‐Petasis–Ferrier rearrangement sequence. Complementary dispersion‐corrected density functional theory (DFT) studies provided an accurate prediction of the reaction enantioselectivity and lend further insight to the origins of stereocontrol. Additionally, a computed potential energy surface around the major transition structure suggests a concerted asynchronous mechanism for the formal annulation.