A transition metal-free [3 + 2] cycloaddition approach for the efficient synthesis of trisubstituted pyrrole derivatives from β-chlorovinyl aldehydes

Abstract

A transition metal-free, Cs₂CO₃-promoted approach has been devised for the efficient synthesis of nitrile-substituted novel pyrrole derivatives from β-chlorovinyl aldehydes. Interestingly, the strategy was also found to be applicable to the synthesis of chromenone-fused pyrrole derivatives. The reaction proceeded through [3 + 2] cycloaddition between diversely substituted aryl propiolonitriles and toluenesulphonylmethyl isocyanide in DMF at ambient temperature. This approach offers several advantages including the use of inexpensive and readily available starting materials, wide substrate scope, operational simplicity, short reaction times (15 min–1.5 h), high atom economy, sustainable reaction conditions and high product yields. The strategy has been found to be amenable for gram-scale synthesis, and the scope of the strategy has been demonstrated for the synthesis of a diverse library of novel pyrrole derivatives with yields of up to 91%. The generated pyrrole derivatives are amenable for late-stage functionalisation and functional group interconversion.