PREPARATION AND USE OF C2-SYMMETRICAL BIS(PHOSPHOLANES) - PRODUCTION OF ALPHA-AMINO-ACID DERIVATIVES VIA HIGHLY ENANTIOSELECTIVE HYDROGENATION REACTIONS

A new class of chiral C2-symmetric bis(phospholane) ligands has been prepared and used in rhodium-catalyzed asymmetric hydrogenation reactions. We describe a practical, one-pot procedure which utilizes enantiomerically pure 1,4-diol cyclic sulfates 4 for the preparation of a homochiral series of 1,2-bis(phospholano)ethanes 1 and 1,2-bis(phospholano)benzenes (DuPHOS) 2. Cationic rhodium complexes bearing these new ligands behave as very efficient catalyst precursors for the asymmetric hydrogenation of a broad range of alpha-(N-acylamino)acrylate (enamide) substrates 5. Significantly, a variety of unnatural and nonproteinaceous alpha-amino acid derivatives 6 were obtained directly with enantioselectivities approaching 100% ee when using the DuPHOS ligands 2. Substrate-to-catalyst ratios of 10 000 were routinely used, and ratios as high as 50 000 were demonstrated in these reactions. Details of the DuPHOS-Rh-catalyzed hydrogenations are discussed.