Open AccessCatalytic Enantioselective Synthesis of α-Difunctionalized Cyclic Sulfones
Author(s) -
Eleanor Bowen,
Gillian Laidlaw,
Bethany C. Atkinson,
Timur A. McArdle-Ismaguilov,
Vilius Franckevičius
Publication year - 2022
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.2c01240
Subject(s) - chemistry , enantioselective synthesis , tsuji–trost reaction , kinetic resolution , palladium , allylic rearrangement , combinatorial chemistry , catalysis , alkylation , drug discovery , organic chemistry , biochemistry
As saturated heterocyclic building blocks become increasingly popular in medicinal chemistry and drug discovery programs, expansion of the synthetic toolkit to novel stereofunctionalized heterocycles is a priority. Herein, we report the development of a palladium-catalyzed decarboxylative asymmetric allylic alkylation reaction to access a broad range of enantioenriched α-difunctionalized 5- and 6-membered sulfones from easily accessible racemic starting materials. The allylic alkylation step was found to occur with high levels of enantioselectivity as a result of a palladium-mediated dynamic kinetic resolution of E / Z enolate intermediates. This methodology paves the way to hitherto unexplored stereodefined cyclic sulfones for medicinal chemistry applications.