Transition Metal-free [3+2] Cycloaddition Approach towards 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 found applicable to the synthesis of chromenone fused pyrrole derivatives also. 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 time (15 min-1.5 h), high atom economy, sustainable reaction conditions and high product yields. The strategy has been found amenable to 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 upto 91%. The generated pyrrole derivatives are amenable to late stage functionalisation and functional group interconversion.