Restricted Conformation of a Hydrogen Bond Mediated Catalyst Enables the Highly Efficient Enantioselective Construction of an All-Carbon Quaternary Stereocenter

Abstract

A highly active catalyst for the enantioselective Friedel–Crafts alkylation of indoles with β,β-disubstituted nitroalkenes is reported, allowing catalyst loadings down to 0.05 mol % for this challenging transformation, providing useful synthetic building blocks with an all-carbon quaternary stereocenter. The catalyst is based on a bis-cyclometalated iridium(III) complex as a structural template, and through the ligand sphere it forms hydrogen bonds with the two substrates. Starting from a previous design (Angew. Chem. Int. Ed. 2013, 52, 14021), the catalyst was rendered C2-symmetrical in order to maximize the atom economy of this catalyst scaffold (two catalytic centers per iridium complex), and, most importantly, rational design was applied to restrict the conformational freedom of a key hydrogen bond acceptor, being responsible for activating the indole nucleophile and bringing it in an ideal position for the presumed ternary transition state.