Homochiral Covalent Organic Framework for Catalytic Asymmetric Synthesis of a Drug Intermediate.

()-2-(2-Chlorophenyl)-2-(6,7-dihydrothieno[3,2-]pyridin-5(4)-yl)acetonitrile (()-) is a key intermediate in the synthesis of ()-clopidogrel, which is one of the most saleable worldwide antiplatelet and antithrombotic drugs. We show herein a facile method for the direct synthesis of ()- via Strecker reaction using a homochiral covalent framework catalyst in a heterogeneous way. The asymmetric synthesis involves a photothermal-conversion-triggered, thermally driven reaction which affords ()- in 98% yield with 94% enantiomeric excess under visible-light irradiation. Furthermore, the above approach is readily extended to a gram-scale level on a fixed-bed continuous-flow model reactor. The potential utility of this strategy is highlighted by the preparation of many more other types of chiral drugs and drug intermediates in a green and facile way.