Formation of All-Carbon Quaternary Centers via Enantioselective Pd-Catalyzed α-Vinylation of γ-Lactams

Creators: Moghadam, Farbod A.; Barbor, Jay P.; Chan, Melinda; Jette, Carina; Sakurai, Shunya; Stoltz, Brian M.¹

1. California Institute of Technology

Abstract

Herein, we report an enantioselective vinylation of α-substituted γ-lactams that forges quaternary centers in up to 59% yield with 94% ee. The use of canonically inactive vinyl chloride electrophiles afforded the highest yields and levels of stereoselectivity, and a range of trisubstituted vinyl chlorides were found to be proficient in promoting this transformation. These stereogenic products could be further elaborated to functionally rich scaffolds, thereby highlighting the synthetic utility of this process.

Copyright and License

CC-BY-NC-ND 4.0 .

Acknowledgement

The authors would like to thank Dr. Mona Shagholi (Caltech) for mass spectrometry assistance and Dr. Scott Virgil (Caltech) for assistance with instrumentation.

Data Availability

The data underlying this study are available in the published article and its Supporting Information.

Accession Codes: CCDC 2375577 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

Supplemental Material

Experimental procedures, spectroscopic data (¹H NMR, ¹³C NMR, IR, HRMS), and SFC and HPLC data: ol4c02551_si_001.pdf (4.76 MB)

Funding

The NIH-NIGMS (R01GM080269 and R35GM145239), Heritage Medical Research Investigators Program, and Caltech are thanked for their support of our research program.

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