Mechanistic investigations of an enantioselective hydrogenation catalyzed by a ruthenium-BINAP complex. 1. Stoichiometric and catalytic labeling studies

The enantioselective hydrogenation of (Z)-methyl alpha-acetamidocinnamate ((Z)-MAC) is catalyzed by [Ru((R)-BINAP)(H)(MeCN)(n)(sol)(3-n)](BF4) (2, n = 0-3, sol = acetone or methanol, (R)-BINAP = (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) in up to 94% ee (R). The mechanism of this catalytic hydrogenation was investigated using in situ NMR spectroscopy, and by comparing the stereochemistry and regiochemistry of deuterium-labeling studies carried out on the catalytic reaction to those carried out on an isolated, possible catalytic intermediate. The isolated species is the olefin-hydride insertion product, [Ru((R)-BINAP)-((S)-MACH)(MeCN)](BF4) ((S-C alpha)-1). Compound (S-C alpha)-1 is the only species present in detectable amounts, by H-1 and P-31 NMR spectroscopy, during the catalytic hydrogenation at room temperature. The absolute configuration at the stereogenic alpha-carbon of MACH is the same (assuming stereospecific replacement of ruthenium with hydrogen) as that of the major enantiomer of the catalytic hydrogenation ((R)-N-acetylphenyl alanine methyl ester ((R)-MACH(2))). Results obtained from the stoichiometric hydrogenolysis and deuteriolysis of (S-C alpha)-1, from the catalytic deuteration of (E)-MAC and (Z)-MAC, and from the reaction of (S-C alpha)-1 with excess (Z)-MAC-Me-d(3) all indicate that formation of (S-C alpha)-1 is rapid and reversible prior to the irreversible hydrogenolysis of the ruthenium-carbon bond. The sum of the stereoselectivities and regioselectivities of the formation and hydrogenolysis of(SCalpha)-1 equals the stereoselectivity and regioselectivity of the catalytic hydrogenation. Solvolysis of the ruthenium-carbon bond occurs to less than 4% during the catalytic hydrogenation carried out in methanol. Removal of MeCN from the catalyst system has no effect on the enantioselection of the catalytic hydrogenation.