Catalytic asymmetric hydrogenation of alpha-(acetamido)acrylates using TRAP trans-chelating chiral bisphosphine ligands: Remarkable effects of ligandP-substituent and hydrogen pressure on enantioselectivity

The catalytic asymmetric hydrogenation of alpha-(acetamido)acrylates was ca rried out with the rhodium complexes prepared from [Rh(cod)(2)]BF4 and tran s-chelating chiral bisphosphine ligands, (S,S)-2,2'-bis[(R)-1-(dialkylphosp hino)ethyl]-1,1'-biferrocenes [(R,R)-(S,S)-TRAPs]. In the reaction of beta -unsubstituted or beta -monosubstituted alpha-(acetamido)acrylates [(E)-RCH =C(NHAc)CO2Me], the selectivity for (R)-hydrogenation product increased wit h decreasing steric demand of the substrate beta -substituent and the ligan d P-substituent as well as decreasing hydrogen pressure. The selectivity fo r the (R)-product in the reaction with EtTRAP-rhodium catalyst at 60 degree sC and 0.5 kg cm(-2) of hydrogen pressure was as follows: R = H, 96% ee; R = Me, 92% ee; R = Ph, 77% ee; R = i-Pr, 57% ee. The remarkable steric and p ressure effects caused a dramatic reversal of enantioselectivity in the rea ction of methyl 2-(N-acetylamino)cinnamate (R = Ph). For example, the selec tivity of 87% (R) with EtTRAP at 60 degreesC and 0.1 kg cm(-2) of hydrogen pressure has reversed to 92% (S) with i-B uTRAP at 15 degreesC and atmosphe ric hydrogen pressure. Hydrogenation of the beta,beta -disubstituted alpha- (acetamido) acrylates proceeded smoothly at 15 degreesC and atmospheric hyd rogen pressure with high enantioselectivity in favor of the 2S-isomers when EtTRAP or BuTRAP was employed as the chiral ligand.