Bridging the incompatibility gap in dual asymmetric catalysis over a thermoresponsive hydrogel-supported catalyst

The integration of dual asymmetric catalysis is highly beneficial for the synthesis of organic molecules with multiple stereocenters. However, two major issues that need to be addressed are the intrinsic deactivation of dual-species and the extrinsic conflict of reaction conditions. To overcome these concerns, we have utilized the compartmental and thermoresponsive properties of poly(N-isopropylacrylamide) (PNIPAM) to develop a cross-linked PNIPAM-hydrogel-supported bifunctional catalyst. This catalyst is designed with Rh(diene) species situated on the outer surface and Ru(diamine) species positioned within the interior of the hydrogel. The compartmental function of PNIPAM in the middle overcomes intrinsic mutual deactivations between the dual-species. The thermoresponsive nature of PNIPAM allows for precise control of catalytic pathways in resolving external conflicts by controlling the reaction switching between an Rh-catalyzed enantioselective 1,4-addition at 50 degrees C and a Ru-catalyzed asymmetric transfer hydrogenation (ATH) at 25 degrees C. As we envisioned, this sequential 1,4-addition/reduction dual enantioselective cascade reaction achieves a transformation from incompatibility to compatibility, resulting in direct access to gamma-substituted cyclic alcohols with dual stereocenters in high yields and enantio/diastereoselectivities. Mechanistic investigation reveals a reversible temperature transition between 50 degrees C and 25 degrees C, ensuring a cascade process comprising a 1,4-addition followed by the ATH process. Dual asymmetric catalysis is powerful for the synthesis of multi-stereocenter molecules, however, the integration of dual catalysts remains challenging due to the intrinsic deactivation of dual-species and extrinsic conflict of reaction conditions. Here, the authors develop a compartmental and thermoresponsive poly(N-isopropylacrylamide)-hydrogel-supported bifunctional catalyst to overcome these challenges.