Continuous-Flow Enantioselective Hydrogenative Enyne Cyclization with Chiral Heterogeneous Rh Catalysts

Continuous-flow hydrogenations provide greatly improved reaction efficiency due to the efficient mass-transfer between heterogeneous catalysts and hydrogen gas. However, reported flow hydrogenations were limited to only simple functional group transformations, and the development of sophisticated catalysis such as enantioselective reductive C–C bond formations remains challenging. Herein, we have developed continuous-flow enantioselective cyclization of 1,6-enynes using chiral heterogeneous catalysts supported on heteropoly acid/amine-functionalized SiO2 composites developed in our group. Investigations under continuous-flow conditions revealed that the tuning of the structure of heteropoly acids and amines could improve the catalyst performance. A variety of substrates could produce products with high yields and enantioselectivities under optimized reaction conditions without leaching of the Rh catalyst. Mechanistic studies revealed the cause of catalyst deactivation of this transformation.