Homologation of Isocyanates with Lithium Carbenoids: A Straightforward Access to alpha-Halomethyl- and alpha,alpha-Dihalomethylamides

作者：Pace Vittorio^*; Castoldi Laura; Mamuye Ashenafi Damtew; Holzer Wolfgang

来源：Synthesis (Germany), 2014, 46(21): 2897-2909.

DOI：10.1055/s-0034-1379209

• amides
• carbenoids
• lithiation
• halides
• nucleophilic addition

Treatment of widely available isocyanates with monohalolithium and dihalolithium carbenoids provides a valuable protocol for the one-pot preparation of -halo- and ,-dihaloacetamide derivatives. While monohalolithium carbenoids can be prepared by a smooth lithium-halogen exchange, the preparation of the corresponding dihalo compounds 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%26apos;s imidoyl triflate activation of a secondary amide to the synthesis of an -chloro ketone and N-15 NMR data for selected compounds.

• 出版日期2014-11