Starting from cheap, easily available building blocks, different benzylidene pyrrolin-4-one derivatives were prepared for the application in stereoselective organocatalyzed reactions. Although the synthesis of similar compounds was known from the literature, much effort was employed to successfully optimize synthesis of various benzylidene pyrrolin-4-one derivatives. Under optimized reaction conditions large scale preparation of benzylidenic pyrrolin-4-one heterocycles was enabled.
One-pot two-step organocatalyzed asymmetric sulfa-Michael/aldol cascade reactions were performed. Various arylidene pyrrolin-4-one derivatives were reacted with 1,4-ditian-2,5-diol in the presence of a quinine organocatalyst. The product of this reaction were new spirocyclic pyrrolin-4-ones. The reaction enables the construction of three new stereocenters, one of which is a quaternary spiro-stereocenter. Reactions proceeded with relatively high diastereoselectivity (73:15:12 – 93:7 d.r.) and enantioselectivity (66 % – >99 % e.e.).
Formation of novel spirocyclic pyrrolin-4-ones was tested also with additional, less frequently applied quinine organocatalysts. With this additional organocatalysts and control experiments, the effect on enantiomeric excess under different isolation procedures was investigated.
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