Exploring Stereogenic Phosphorus:  Synthetic Strategies for Diphosphines Containing Bulky, Highly Symmetric Substituents

Diphosphine ligands bearing highly symmetric, bulky substituents at a stereogenic P atom were prepared, exploiting established protocols, which include the use of chiral synthons such as 3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaphospholidine-2-borane (3a) and phenylmethylchlorophosphine borane (10) and the enantioselective deprotonation of dimethylarylphosphine boranes. However, only (Bu t )(Me)PCH2CH2P(Bu t )Me (8a) could be prepared from 3a. The diphosphines (S,S)-1,2-bis(mesitylmethylphosphino)ethane, ((S,S)-8b) and (S,S)-1,2-bis(9-anthrylmethylphosphino)ethane ((S,S)-8c), which contain 2,6-disubstituted aryl P-substituents, were prepared by Evans' sparteine-assisted enantioselective deprotonation of P(Ar)(Me)2(BH3) (Ar = mesityl or 9-anthryl), but the enantioselectivity did not exceed 37% ee. The asymmetrically substituted, methylene-bridged diphosphine (2R,4R)-(Ph)(CH3)PCH2P(Mes)(CH3) ((2R,4R)-12) (Mes = mesityl) was prepared by the newly developed stereospecific reaction of the enantiomerically pure chlorophosphine borane PCl(Ph)(Me)(BH3) (10) with the racemic, monolithiated dimethylmesitylphosphine borane P(Mes)(Me)(CH2Li)(BH3). Diastereomerically pure (2R,4R)-12 was obtained with 86% ee. The rhodium(I) derivatives [Rh(COD)(P−P)]BF4 containing the diphosphine ligands 8a, 8b, and 12, as well as the previously reported (S,S)-1,2-bis(1-naphthylphenylphosphino)ethane ((S,S)-8d), were prepared and tested in the enantioselective catalytic hydrogenation of acetamidocinnamates. The best catalytic result (98.6% ee) was obtained with [Rh(COD)(8d)]+ as catalyst and methyl Z-α-acetamidocinnamate as substrate. Some of the catalytic results are discussed in terms of the preferred conformations of the substituents at phosphorus, as calculated by molecular modeling.