Oligosubstituted Pyrroles Directly from Substituted Methyl Isocyanides and Acetylenes

• Published in: Chemistry : a European journal Vol. 15; no. 1; pp. 227 - 236
• Main Authors: Lygin, Alexander V., Larionov, Oleg V., Korotkov, Vadim S., de Meijere, Armin
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.01.2009; Wiley
• Subjects: Alkynes - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; copper; Copper - chemistry; Cyanides - chemical synthesis; Cyanides - chemistry; cycloaddition; isocyanides; Physical Sciences; pyrroles; Pyrroles - chemical synthesis; Pyrroles - chemistry; Science & Technology; 1,3-DIPOLAR CYCLOADDITIONS; INSERTION; ASYMMETRIC-SYNTHESIS; SYNTHETIC REACTIONS; catalysis; ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; TERMINAL ALKYNES; pyrroles; isocyanides; cycloaddition; COMPLEX CATALYSTS; DNA GYRASE; copper; MULTICOMPONENT SYNTHESIS; ALPHA-METALATED ISOCYANIDES
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200801395

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).