Thio FCMA Intermediates as Strong Acyl Donors: A General Solution to the Formation of Complex Amide Bonds

摘要

Following explorations into the chemistry of isonitriles, we were recently able to develop a new line of methodology which we consolidate in the expression, two-component coupling (2CC). The 2CC progression presumably commences via the reaction of an isonitrile (2) with a carboxylic acid (1), thereby generating a formimidate carboxylate mixed anhydride (3). For ease of communication, we refer to such a structure as an "FCMA". While no FCMA has been fully characterized, Rebek has brought to bear impressive evidence as to their existence in special settings. It seems that, under the usual reaction conditions, the oxy FCMA (3) is produced slowly and is disfavored at equilibrium. However, at higher temperatures under microwave mediation, the oxy FCMA, as its Z stereoisomer (3-Z), apparently undergoes a 1,3-O→N acyl transfer to generate an iV-formylamide (4), the end point of the 2CC reaction.