Direct Catalytic Enantioselective Friedel-crafts Alkylation Of Pyrrole With Chalcone Derivatives Via A Dinuclear Zinc Catalyst

Over the past decade, the catalytic asymmetric Friedel-Crafts alkylations ofheteroaromatic compounds with simple α,β-unsaturated aldehydes and ketones haveattracted considerable interest because of their ability to construct enantiomericallyenriched alkylated heteroarenes which exhibit biological activities andpharmaceutical values. Among these remarkable advances, reports about the use ofpyrrole and chalcone derivatives as substrates remain relatively rare. Herein we reportthe use of bis-ProPhenol dinuclear zinc complex as an efficient catalyst to promoteasymmetric Friedel-Crafts alkylations of pyrrole with chalcone derivatives, tosynthesize2-substituted pyrroles with a chiral carbon atom in the α-position. Ourmain research contents are summarized as follows:1) A battery of chiral amino alcohol ligands were prepared to conduct theasymmetric Friedel-Crafts alkylation of pyrrole with chalcone derivatives, and chiralsemi-azacrown ether L5was proved to be the optimal ligand. Under the catalysis of15mol%L5-ZnEt2complex the reaction proceeded smoothly in THF at20℃,affording the desired pyrrole adducts in good to high yields (up to>99%) and withexcellent enantioselectivities (up to>99.9%ee). More than twenty kinds of chalconederivatives were examined to demonstrate the scope and potential of this reaction,and most of them obtained satisfactory results (above99%yield and99%ee).2) Based on the literature and our experimental data, a possible mechanism wasproposed.