Cobalt-Catalyzed Enantio- and Regioselective C(sp3 )-H Alkenylation of Thioamides
Lucia Staronova1, Ken Yamazaki1,2, Xing Xu1
1Department of Chemistry, Chemistry Research Laboratory University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Abstract:
An enantioselective cobalt-catalyzed C(sp3 )-H alkenylation of thioamides with but-2-ynoate ester coupling partners employing thioamide directing groups is presented. The method is operationally simple and requires only mild reaction conditions, while providing alkenylated products as single regioisomers in excellent yields (up to 85 %) and high enantiomeric excess [up to 91 : 9 enantiomeric ratio (er), or up to >99 : 1 er after a single recrystallization]. Diverse downstream derivatizations of the products are demonstrated, delivering a range of enantioenriched constructs. Extensive computational studies using density functional theory provide insight into the detailed reaction mechanism, origin of enantiocontrol, and the unusual regioselectivity of the alkenylation reaction.
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