Abstract The lipase Novozym435 (0.6% w/w) was used in tandem with organocatalysts in a first vinyl/isopropenyl acetate-mediated aldol reaction. The reaction was facilitated through the lipase-catalyzed in situ generation of acetaldehyde/acetone. The important features of the present methodology include the mild and facile reaction conditions, regenerability of the lipase, comparatively high yields and minimal side product formation.