Catalytic Regio- and Enantioselective Hydroformylation of Trisubstituted Alkenes to Construct α-Quaternary Lactams

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Abstract
Developing novel stereoselective methods for α-quaternary lactams is of significant importance for advancing structure-activity studies, discovering new antibiotics, and synthesizing diverse functional compounds for synthetic and materials research. Herein, we have successfully developed a Rh-catalyzed asymmetric hydroformylation (AHF) of trisubstituted olefins, overcoming both the inherent inertness of trisubstituted olefins in such reactions and Keulemans' rule, efficiently generating diverse β- and γ-lactams bearing an α-quaternary stereocenter with exceptional regio- and enantioselectivities (up to >20:1 rr, 99% ee). This mild and operationally simple reaction proceeds in an atom-economic manner with a broad substrate scope, along with excellent functional-group tolerance, scalability, and product diversification. Computational studies suggest that the enantio- and/or regioselectivity may originate from the Rh-C bonding along with the noncovalent interactions between the Boc group on the substrate and Ph groups on the ligand.
Funding Information
  • National Key Research and Development Program of China (2021YFA0910800)
  • Innovative Team of Universities in Guangdong Province (2020KCXTD016)
  • Chemistry and Chemical Engineering Guangdong Laboratory (2011006, 2132013)

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