Oligosubstituted Pyrroles Directly from Substituted Methyl Isocyanides and Acetylenes

The formal cycloaddition of α‐metallated methyl isocyanides 1 onto the triple bond of electron‐deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3. The scope and limitations of this reaction (24 examples, 25–97 % yield) are reported along with an optimization of the reaction conditions and a rationalization of the mechanism. In addition, a related newly developed CuI‐mediated synthesis of 2,3‐disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides is described (11 examples, 5–88 %yield). Convenient pyrrole syntheses: Two new protocols have been developed for one‐pot, one‐step formal [3+2] cycloadditions of substituted methyl isocyanides onto the triple bond of either acceptor‐activated internal or non‐activated terminal acetylenes leading to 2,3,4‐trisubstituted and 2,3‐disubstituted pyrroles, respectively (see scheme).