Cobalt‐Catalyzed Enantio‐ and Regioselective C(sp3)−H Alkenylation of Thioamides

• Published in: Angewandte Chemie International Edition Vol. 63; no. 13; pp. e202316021 - n/a
• Main Authors: Staronova, Lucia, Yamazaki, Ken, Xu, Xing, Shi, Heyao, Bickelhaupt, F. Matthias, Hamlin, Trevor A., Dixon, Darren J.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 22.03.2024; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Chemistry; Chemistry, Multidisciplinary; Cobalt; Cobalt Catalysis; C−H Alkenylation; Density Functional Calculations; Density functional theory; Enantiomers; Enantioselective; Physical Sciences; Reaction mechanisms; Recrystallization; Regioselectivity; Science & Technology; Thioamide; Cobalt Catalysis; ANNULATION; ARENES; AMIDATION; C-H FUNCTIONALIZATION; ALKYNES; C-H Alkenylation; DIRECTING GROUPS; Density Functional Calculations; Enantioselective; Thioamide; N BOND FORMATION; SCREENING MODEL; MOLECULAR-ORBITAL THEORY; ACTIVATION STRAIN MODEL; C−H Alkenylation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202316021

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. A cobalt‐catalyzed enantioselective C(sp3)−H alkenylation of thioamides with alkynoate esters is presented. The reaction provides alkenylated products in high yields and selectivities that are primed for diverse downstream derivatizations.