Reductive Alkylation of Tertiary Lactams via Addition of Organocopper (RCu) Reagents to Thioiminium Ions

A simple procedure for the conversion
of tertiary lactams to 2-monoalkylated
cyclic amines is described. The reaction sequence involves conversion
of a lactam to a thioiminium ion followed by reaction with an organocopper
(RCu) reagent and final reduction with triacetoxyborohydride. The
reaction is high yielding and shows an excellent functional group
tolerance. Its utility is demonstrated by a rapid synthesis of indolizidine
167B. The excellent chemoselectivity of the process, where only monoalkylation
products are formed, is rationalized by a mechanism involving the
formation of a transient enamine.