Catalyst-controlled diastereoselective hetero-Diels---Alder reactions. Thiourea-catalyzed enantioselective hydrophosphonylation of imines

I. The diastereoselective hetero-Diels---Alder reaction between Danishefsky's diene and chiral aldehydes is catalyzed by chiral chromium-Schiff base complexes. The stereochemical outcome of these reactions is effectively controlled by the chiral catalysts. Reaction conditions were optimized to allow optically-active aldehydes bearing labile alpha-stereocenters to undergo highly diastereoselective cycloadditions to provide enantiomerically and diastereomerically enriched dihydropyranone products. This methodology provides selective access to stereochemically elaborate dihydropyranone derivatives that are not readily accessible using substrate-controlled diastereoselective reactions or through simple enantioselective reactions of achiral substrates. Judicious choice of aldehyde and catalyst enantiomers allows for the selective synthesis of any of the four possible stereoisomeric products.; II. Chiral ureas and thioureas catalyze the enantioselective hydrophosphonylation of N-benzyl imines. Extensive optimization of both the catalyst and phosphite nucleophile resulted in an efficient and highly enantioselective reaction. This new methodology provides general access to a wide range of highly enantiomerically-enriched alpha-amino phosphonates. The hydrophosphonylation products are readily deprotected by hydrogenolysis, providing straightforward access to free alpha-amino phosphonic acids in highly enantioenriched form. In addition, the first asymmetric catalytic synthesis of alpha-aryl-alpha-amino phosphonates was achieved.