Enantioselective Pyrrole Alkylations

Significance

A Sc(OTf)₃/(inda)pybox catalyst was used to achieve the asymmetric Michael-type addition of unprotected pyrroles 2 on α,β-unsaturated 2-acyl imidazole systems 1. The alkylated pyrroles 6 were obtained with high enantioselectivity and tolerated a wide range of β-substituents on the Michael acceptor. Interestingly, higher catalyst loadings led to lower enantioselectivities. This method also provides access to 2-substituted indoles 5, after chemical oxidation of the alkylated parent 4,7-dihydropyrrole 4. The imidazole moiety can be cleaved to the ester 10 in high yield after activation of the imidazole via N-alkylation.