Asymmetric Hydrogenation Catalyzed by a Rhodium Complex of (R)-(tert-Butylmethylphosphino)(di-tert-butylphosphino)methane:  Scope of Enantioselectivity and Mechanistic Study

Abstract

The rhodium complex of (R)-(tert-butylmethylphosphino)(di-tert-butylphosphino)methane used in Rh-catalyzed asymmetric hydrogenation of representative substrates 3-14 demonstrated high catalytic activity coupled with wide scope and nearly perfect enantioselectivity. Mechanistic studies (NMR and DFT computations) were carried out in order to investigate the mechanism of the enantioselection in the asymmetric hydrogenation of (Z)-alpha-acetamidocinnamate (3). Although catalyst-substrate complexes 15a,b with the double bond coordinated near the non-"chiral" phosphorus atom were formed as kinetic products upon the addition of 3 to solvate complex 2 at -100 degrees C, they rapidly rearranged to more stable isomers 15c,d with the double bond coordinated near the "chiral" phosphorus atom. The thermodynamic and kinetic parameters of the interconversion between 15c and 15d were determined by NMR; mainly, the interconversion occurred intramolecularly via nonchelating catalyst-substrate complexes 16. The equilibrium between 15d and 16d was directly observed from NMR line shape changes at temperatures ranging from -100 to -40 degrees C, whereas no such equilibrium was observed for 15c. This result was accounted for computationally by determining the corresponding transition states for the methanol insertion into 15c,d. Three sets of experiments of the low-temperature hydrogenation of different catalyst-substrate complexes gave the same order and sense of enantioselectivity (97% ee (R)) even in the case when 15c, having Re-coordinated double bond, was hydrogenated under the conditions precluding its isomerization to 15d. It was concluded that the hydrogenation of 15c,d does not occur directly, but is preceded by the dissociation of the double bond to result in the more reactive species 16. This indicates that enantioselection must occur at a later step of the catalytic cycle. DFT computations of association and migratory insertion steps suggest that enantioselection takes place during the association step when chelating dihydride 19d.MeOH is formed from nonchelating dihydride 18d.

Mechanistic analysis of the transition metal-catalyzed hydrogenation of imines and functionalized enamines

“…The two kinetics isomers resulting from the coordination of acetamidocinnamate, adapted from Ref. [75]. electronic benefit is lost and the amido group comes into a hindered quadrant.…”

“…Very recent studies carried out by Imamoto and coworkers [74,75] allow to have a deeper insight onto the mechanism of the reaction of H 2 with the [(diphos*)Rh(substrate)] + intermediates taking into account the crucial role of the solvent. Indeed, starting from the chiral diphosphine ligand (t-Bu) 2 PCH 2 P*(CH 3 )(t-Bu) which presents a constrained bridge between the two nonequivalent phosphorus atoms, low temperature NMR studies and theoretical calculations of the methanol-solvated species shed light on the intramolecular isomerization process between the two R and S-(␣)-acetamidocinnamate complexes to provide an enantiomer with 97% e.e.…”

“…Reaction pathway giving the (S)-isomer, adapted from Ref. [75]. hedral stereoisomer 60 which precedes the irreversible migratory insertion step giving species 61 (Scheme 31).…”

Role of the reaction intermediates in determining PHIP (parahydrogen induced polarization) effect in the hydrogenation of acetylene dicarboxylic acid with the complex [Rh (dppb)]+ (dppb: 1,4-bis(diphenylphosphino)butane)

“…The hydrogenation mechanism of unsaturated substrates using cationic Rh(I) complexes has been extensively investigated by means of kinetic studies, 1 density functional theory (DFT) calculations, [2][3][4] and, more recently, ParaHydrogen Induced Polarization (PHIP). [5][6][7] The interest in this class of catalysts, in particular with chelating phosphine, namely [(P-P)Rh(I)(diene)], for parahydrogenation reactions is due to the high polarization level that can be achieved on both 1 H and heteronuclear signals.…”

Asymmetric Hydrogenation

“…Among them, complex 4 is energetically most stable, is preferentially formed, and undergoes migratory insertion via the lowest transition state, resulting in the formation of the (R)-hydrogenation product. The origin of the enantioselection process has also been studied using MAC and Trichickenfootphos, a C1-symmetric three-hindered phosphine ligand [31,32]. In this case, two of the four possible diastereomeric catalyst-substrate complexes are thermodynamically stable and exist in a ratio of about 1:1.…”