Cobalt(iii)–salen decorated stereoregular optically active helical polyisocyanides enable highly effective cooperative asymmetric catalysis toward the kinetic resolution of epoxides

Abstract

Static one-handed helical polymers can serve as an ideal catalytic platform toward chiral synthesis. As a demonstration of helical polyisocyanides in asymmetric catalysis, we report a novel strategy to facilitate asymmetric cooperative catalysis for the kinetic resolution of epoxides with TMSN₃ using one-handed polyisocyanide-supported Co(III)–salen catalysts. Co(III)–salen is decorated with polyisocyanides to produce the polymer-supported catalyst P1–Co–N₃. Owing to the rigid helical backbone of the polyisocyanide skeleton, spatially adjacent Co(III)–salen pendants are arranged with a distance of ∼1.2 nm so that the epoxide and TMSN₃ can undergo dual activation in an amplified chiral environment. The catalytic performance is investigated via the kinetic resolution for a series of terminal epoxides through enantioselective ring-opening with TMSN₃. P1–Co–N₃ exhibits high catalytic activity and enantioselectivity, producing the desired products in high enantiomeric excesses and good yields at a low catalyst loading (0.6 mol%). In contrast, a small molecular control, S1–Co–N₃, performs poorly owing to the absence of a preorganized catalytic dimer. Moreover, this polyisocyanide-based catalyst exhibits good functional group tolerance and stable activity in multiple recycles. To demonstrate its potential application in the asymmetric synthesis of chiral drugs, we conducted a gram-scale asymmetric synthesis of β-amino acid derivatives via this kinetic resolution method as the essential step.