Enantioselective synthesis of 2,3-dihydrofurans using a bifunctional quinine/squaramide organocatalyst

Abstract

Asymmetric organocatalytic domino type Michael-S(N)2 reactions give access to enantiomerically enriched dihydrofuran derivatives that can be used as valuable chiral building blocks. A variety of alpha-bromonitroalkenes and 1,3-dicarbonyl compounds were allowed to react under optimized conditions, in the presence of a bifunctional quinine-derived sterically encumbered squaramide (H-bond donor) organocatalyst. The conditions developed in this article have great advantages over the methods known in the literature in terms of reaction duration (1-6 h vs. 24-96 h) and reaction temperature (room temperature vs. -20 degrees C to -50 degrees C) giving rise to quite diastereoselective products with good enantioselectivities up to 97% ee.