Homologation of isocyanates with lithium carbenoids: a straightforward access to α-​halomethyl- and α,​α-​dihalomethylamides

Treatment of widely available isocyanates with monohalolithium and dihalolithium carbenoids provides a valuable protocol for the one-​pot prepn. of α-​halo- and α,​α-​dihaloacetamide derivs. While monohalolithium carbenoids can be prepd. by a smooth lithium-​halogen exchange, the prepn. of the corresponding dihalo compds. proved to be highly dependent on the base used to realize the deprotonation, with lithium 2,​2,​6,​6-​tetramethylpiperidine emerging as optimal. The clear advantages of the procedure are: (a) broad scope of isocyanates that can be employed; (b) preservation of the optical purity when chiral materials are used; (c) divergent access to different haloamides by simply selecting the homologating agents. We also report an application of Charette's imidoyl triflate activation of a secondary amide to the synthesis of an α-​chloro ketone and 15N NMR data for selected compds.