Asymmetric Organocatalytic Sulfoxidations And Phospha-Michael Reactions By Hydrogen-Bonding Activation

Hydrogen bonding to an electrophile serves to decrease the electron density of thisspecies, activating it toward nucleophilic attack. Some small molecule chiralhydrogen-bond donors were prepared following the reported procedures, which havebeen successfully applied to promoting the asymmetric phospha-Michael addition ofdiethyl phosphites to isatylidenemalononitriles and asymmetric oxidation of aryl alkylsulfides and aldehyde-derived1,3-dithianes.In the first part,(R)-BINOL derived chiral phosphoric acids have been explored asorganocatalysts for the asymmetric oxidation of a series of aryl alkyl sulfides and1,3-dithianes derived from aldehydes with aqueous H2O2as the terminal oxidant. Theenantiomerically enriched sulfoxides are obtained in moderate to excellent yield (up to99%) with excellent diastereoselectivity (up to>99:1dr) and moderate to goodenantioselectivity (up to91:9er). In particular, the present protocol stereoselectivelyprovides an efficient access to enantiomerically enriched aryl alkyl sulfoxides anddithioacetal mono-sulfoxides, which sternly restrains the formation of the undesirablebyproducts of sulfones or disulfoxides. The tracking experiments also verify that thisapproach proceeds via a direct sulfoxidation process, instead of a kinetic resolutionroute by overoxidation of the resulting sulfoxides.α-Functionalized phosphonic acids are valuable intermediates for the preparationof medicinal compounds and synthetic intermediates. An unprecedented and highlyenantioselective organocatalytic synthesis of dialkyl3-(dicyanomethyl)-2-oxoindolin-3-ylphosphonate was achieved through an asymmetric conjugate addition of diethylphosphites to isatylidenemalononitriles catalyzed by DPEN-based bifunctional thiourea.Optically active products bearing quaternary chiral carbon stereocenters were obtainedin high yields (78–98%) with good to excellent enantioselectivities (up to95%ee).Masking of the "N"(e.g., Me-) led to dramatic decrease of the ee values and yields. Four chiral squaramides were synthesized using simple methods. Their catalyticeffects on the asymmetric addition of diethyl phosphite to benzylidenemalononitrilewere evaluated, and it was found that they could promote the reaction with only23%ee.Investigations are still ongoing in our laboratory to utilize other optically smallmolecule as catalysts for this asymmetric transformation.