Microcapsule Enabled Multicatalyst Reaction

Significance

A tandem Henry-Michael reaction by using a phase-isolated multicatalytic system of insoluble microencapsulated amine catalyst 1 and homogeneous nickel catalyst 2 was developed. Thus, the reaction of an aldehyde 3 with nitro­methane (10 equiv) and dimethyl malonate (1 equiv) in the presence of catalysts 1 and 2 (7 mol% each) in methanol-toluene gave 4 in <5-94% yield (9 examples) via the base-promoted nitro­aldol condensation forming 5 and the successive Ni-catalyzed Michael addition of dimethyl malo­nate. An anticonvulsant agent pregabaline (8) was synthesized via the developed catalytic reaction of 6 in 74% overall yield with 72% ee.