Brønsted Acid Catalyzed [6 + 2]-Cycloaddition of 2-Vinylindoles with in Situ Generated 2-Methide-2 H-pyrroles: Direct, Catalytic, and Enantioselective Synthesis of 2,3-Dihydro-1 H-pyrrolizines.

Abstract

We describe herein an organocatalytic, diastereo- and enantioselective [6 + 2]-cycloaddition toward the synthesis of densely substituted 2,3-dihydro-1 H-pyrrolizines bearing three contiguous stereogenic centers which are obtained with good yields, as single diastereomers, and with excellent enantioselectivity. A crucial feature of this one-step process leading to a prominent structural motif in many biologically active natural products is a BINOL-derived phosphoric acid catalyzed reaction of 1 H-pyrrole-2-yl carbinols with 2-vinylindoles via the corresponding hydrogen-bonded chiral 2-methide-2 H-pyrroles.