Versatile Direct Synthesis of Oligosubstituted Pyrroles by Cycloaddition of α‐Metalated Isocyanides to Acetylenes

Abstract

Acceptor‐substituted pyrroles can be prepared from acetylenes and isocyanides in an efficient and direct manner by a formal cycloaddition under basic conditions or, even simpler, in the presence of catalytic amounts of nanosize copper powder or copper(I) benzenethiolate.

Synthesis of 3-hydroxy-2H-iminolactones and 3-hydroxy-2H-pyrrol-2-ones from reaction between isocyanides and methyl-2-acetylacetoacetate

“…[8][9][10] Cycloadditon reactions of this type are unique to isocyanides. The reaction of isocyanides with carbon-carbon double bonds tends to occur in a stepwise manner and is involves a zwitterionic intermediate the ultimate fate of which appears to be dictated by the nature of the original double bond substrate.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] Using the isocyanide carbon atom for synthesis of many cyclic systems in a formal…”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…The regioselectivity may be reversed by changing the catalyst to Cu 2 O, giving instead the product 130 (Scheme 4.38) [193]. A related synthesis of pyrroles involving addition of metallated isocyanides to acetylenes, featuring an intramolecular cycloaddition of an alkene unit with the isocyanide moiety in the initially formed intermediates as the key step, has also appeared [194]. Multi-component processes, which are carried out in a one pot operation, have become increasingly popular tools for pyrrole synthesis in recent years.…”

Cu‐Catalyzed Heterocycle Synthesis

“…Several copper could catalyze the polysubstituted pyrrole formation. Moreover, they also developed a new copper catalyst system for the synthesis of 2,3-disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides in 5-88% yield [16,17]. The regiocontrolled formation of pyrroles via a formal [3+2] cycloaddition of isocyanides and electron-deficient alkynes could be realized in different catalytic system.…”