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

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-N-3. Owing to the rigid helical backbone of the polyisocyanide skeleton, spatially adjacent Co(III)-salen pendants are arranged with a distance of similar to 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-N-3 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-N-3, 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 beta-amino acid derivatives via this kinetic resolution method as the essential step.

Automated summary

Static one-handed helical polymers have been utilized as an ideal platform for chiral synthesis, and a novel strategy utilizing one-handed polyisocyanide-supported Co(III)-salen catalysts has been developed for the asymmetric cooperative catalysis of epoxides. The polymer-supported catalyst P1-Co-N-3 exhibits high catalytic activity and enantioselectivity, producing desired products in high enantiomeric excesses and good yields at a low catalyst loading. This polyisocyanide-based catalyst also shows good functional group tolerance and stable activity in multiple recycles.