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Kinetically Controlled, Highly Chemoselective Acylation of Functionalized Grignard Reagents with Amides by N−C Cleavage
Author(s) -
Li Guangchen,
Szostak Michal
Publication year - 2020
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.201904678
Subject(s) - reagent , acylation , amide , chemistry , combinatorial chemistry , chemoselectivity , grignard reagent , chelation , organic chemistry , cleavage (geology) , catalysis , materials science , fracture (geology) , composite material
The direct transition‐metal‐free acylation of amides with functionalized Grignard reagents by highly chemoselective N−C cleavage under kinetic control has been accomplished. The method offers rapid and convergent access to functionalized biaryl ketones through transient tetrahedral intermediates. The direct access to functionalized Grignard reagents by in situ halogen–magnesium exchange promoted by the versatile turbo‐Grignard reagent ( i PrMgCl ⋅ LiCl) permits excellent substrate scope with respect to both the amide and Grignard coupling partners. These reactions enable facile, operationally simple and chemoselective access to tetrahedral intermediates from amides under significantly milder conditions than chelation‐controlled intermediates. This novel direct two‐component coupling sets the stage for using amides as acylating reagents in an alternative paradigm to the metal‐chelated approach, acyl metals and Weinreb amides.