Mechanistic Investigations of an Enantioselective Hydrogenation Catalyzed by a Ruthenium−BINAP Complex. 1. Stoichiometric and Catalytic Labeling Studies

The enantioselective hydrogenation of ( Z )-methyl α-acetamidocinnamate (( Z )-MAC) is catalyzed by [Ru(( R )-BINAP)(H)(MeCN) n (sol) 3 - n ](BF 4 ) ( 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)](BF 4 ) (( S C α )- 1 ). Compound ( S C α )- 1 is the only species present in detectable amounts, by 1 H and 31 P NMR spectroscopy, during the catalytic hydrogenation at room temperature. The absolute configuration at the stereogenic α-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 -acetylphenylalanine methyl ester (( R )-MACH 2 )). Results obtained from the stoichiometric hydrogenolysis and deuteriolysis of ( S C α )- 1, from the catalytic deuteration of ( E )-MAC and ( Z )-MAC, and from the reaction of ( S C α )- 1 with excess ( Z )-MAC-Me- d 3 all indicate that formation of ( S C α )- 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 ( S C α )- 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.