Remote Stereocontrol via Macrocyclic Transition State in Thiourea-NHC-Catalyzed ε-Michael Addition of Biomass-Derived Furfurals

Remote stereocontrol in catalytic reactions is challenging due to the weakened influence of the catalyst arising from the long distance and conformational flexibility of the linear transition state. Herein, we report the bifunctional thiourea-N-heterocyclic carbene (NHC)-catalyzed remote ε-Michael addition of trienolate intermediates to nitroalkenes, with biomass-derived platform compounds 5-(chloromethyl)furfural (CMF) and 5-(hydroxymethyl)furfural (HMF) derivatives serving as the trienolate precursors. A wide range of high-value-added N-containing chiral products was afforded in good yields with high enantioselectivities. In this protocol, the macrocyclic transition state enabled high levels of remote enantiocontrol through a dual H-bonding network linking the trienolate intermediate and the nitroalkene. Detailed control experiments and density functional theory (DFT) calculations confirmed the significance of the bifunctional thiourea-NHC catalyst.