Dynamic Kinetic Resolution in an Asymmetric Michael-Michael Cascade

Significance

A highly diastereo- and enantioselective Michael-Michael reaction cascade of nitroalkenes and trans-3-(2-mercaptophenyl)-2-propenoic acid ethyl esters catalyzed by a chiral cinchona alkaloid thiourea 1 is described. The process proceeds via non-covalent hydrogen-bond interactions and results in the formation of enantioenriched thiochromanes in good yields of up to 99% and excellent enantioselectivities (er = 96:4 to 99.5:0.5). The observed diastereomeric ratios were >30:1 in the majority of cases. As reason for the high selectivity a dynamic kinetic resolution mediated retro-Michael-Michael-Michael cascade was proposed and confirmed in an experiment.