Sidearm-tuned chiral hypercrosslinked polymer catalysts for high-efficiency asymmetric reactions

The development of novel enantioselective organocatalysts is a captivating area in chiral chemistry. Herein, the chiral porous hypercrosslinked polymer precursor, HCP-AA-Fmoc-(L)Pro, was prepared via a Friedel-Crafts alkylation reaction. Notably, in addition to serving as a protective group, the fluorenyl moiety of Fmoc group undergoes co-crosslinking with the benzene rings of the aromatic amines within the hypercrosslinked polymer framework, thereby constructing a sterically stable environment. Subsequently, based on the deprotection of the 9-fluorenylmethyloxycarbonyl (Fmoc) group, a sidearm group was introduced in situ at the catalytic site, and the chiral hypercrosslinked proline-derived polymer catalysts HCP-AA-DBFBB-(L)Pro was synthesized. By introducing sidearm groups to finely tune the chiral environment, the chiral cavity accommodating substrates and reagents was modulated. This enabled high activity in the asymmetric aldol reaction between cyclohexanone and 4-nitrobenzaldehyde, achieving impressive dr values of up to 99/1 and ee values of 96%. Moreover, the HCP-AA-DBFMO-(L)Pro exhibited high enantioselectivities in various asymmetric reactions, including aldol reaction, Michael addition reaction, and domino reaction. Mechanistic studies by DFT calculation reveal the critical role of various sidearm groups in the asymmetric catalytic reaction. This study provides new insights into the development and construction of chiral organocatalysts, wherein the introduction of the side arm facilitates high enantioselectivity.