Highly Stereoselective Synthesis of Substituted γ-Lactams from Acylsilanes


  • Support has been provided in part by the NSF (CHE-0348979), the PRF (Type G), and Northwestern University. We thank Abbott Laboratories, Amgen, AstraZeneca, GlaxoSmithKline, 3M, and Boehringer-Ingelheim for generous unrestricted research support, Wacker Chemical Corp. and FMCLithium for providing reagents, and Troy Reynolds (NU) for assistance with X-ray crystallography. K.A.S. is a fellow of the Alfred P. Sloan Foundation.


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It takes three: The stereoselective synthesis of highly substituted γ-lactams from amide enolates, acylsilanes, and imines is reported. This multicomponent reaction accesses γ-amino-β-hydroxy amides in a single flask with good yields and excellent levels of diastereoselectivity (see scheme). Exposure of the linear products to microwave irradiation and acidic conditions promotes a cyclization to form the corresponding γ-lactams in excellent yields.