Ruthenium complexes employing axially chiral ligands were found to be effective asymmetrichydrogenation catalysts for the reduction of
,
-unsaturated ene acid
1-E to give
2, a prostaglandin D
2(PGD
2) receptor antagonist. With [(
S-BINAP)Ru(
p-cymene)Cl
2]
2 (
3,
S-BINAP = (
S)-(+)-2,2'-bis(diphenylphospino)-1,1'-binapthyl), it was discovered that low hydrogen pressures (<30 psi) were essential toachieve high enantioselectivities (92% ee). A detailed mechanistic study was undertaken to elucidate thispressure dependence. It was determined that compound
1-E is in a ruthenium-catalyzed equilibrium withendocylic isomer
1-Endo and in photochemical equilibrium with
Z isomer
1-Z. Each isomer could behydrogenated to give
2, albeit with different rates and enantioselectivities. Hydrogenation of
1-Endo with
3 was found to give
2 in high enantiomeric excess, regardless of pressure and at a rate substantially fasterthan that of hydrogenation of
1-E and
1-Z. In contrast, isomers
1-E and
1-Z exhibited pressure-dependentenantioselectivities, with higher enantiomeric excesses obtained at lower pressures. A rationale for thispressure dependence is described. Deuterium labeling studies with
1-Endo and tiglic acid were used toelucidate the mechanism of hydride insertion and product release from ruthenium. Under neutral conditions,protonolysis was the major pathway for metal-carbon cleavage, while under basic conditions, hydrogenolysisof the metal-carbon bond was predominant.