Direct, Enantioselective, and Nickel(II) Catalyzed Reactions of N‐Azidoacetyl Thioimides with Trimethyl Orthoformate: A New Combined Methodology for the Rapid Synthesis of Lacosamide and Derivatives

A direct and highly enantioselective reaction of N ‐azidoacetyl‐1,3‐thiazolidine‐2‐thione with trimethyl orthoformate catalyzed by Tol‐BINAPNiCl 2 in the presence of TESOTf and 2,6‐lutidine is reported. The heterocyclic scaffold can be easily removed by addition of a wide array of amines to give the corresponding enantiomerically pure 2‐azido‐3,3‐dimethoxypropanamides in high yields. Appropriate manipulation of the N ‐benzyl amide derivative...