Mechanistic Study of the Ru-Catalyzed Asymmetric Hydrogenation of Nonchelatable and Chelatabletert-Alkyl Ketones Using the Linear Tridentate sp³P/sp³NH/sp²N-Combined Ligand PN(H)N: RuNH- and RuNK-Involved Dual Catalytic Cycle

Abstract

The linear tridentate sp 3 P/sp 3 NH/sp 2 N ligand PN(H)N ((R)-2′-(diphenylphosphino)-N-(pyridin-2ylmethyl)[1,1′-binaphthalen]-2-amine) exclusively forms fac-[Ru(PN(H)N)(dmso) 3 ](BF 4 ) 2 over the mer isomer with the help of the three strongly π-accepting DMSO ligands. The three different ligating atoms exert a divergent effect on the trans-DMSORu bond strengths, enabling the stereoselective generation of fac-RuH(CH 3 O)(PN(H)N)(dmso) (RuNH). RuNH efficiently hydrogenates both nonchelatable t-butyl methyl ketone (BMK) and chelatable t-butyl methoxycarbonylmethyl ketone (BMCK) in the presence of a catalytic amount of CH 3 OK. The reaction proceeds at the Hsp 3 NRuH bifunctional reaction site of fac-RuH 2 (PN(H)N)(dmso), and high enantioselectivity is attained in a chiral 3D cavity constructed by the sp 3 N trans DMSO, the conformation of which is fixed by a PyC(6)HOS hydrogen bond. We determined the structures of RuNH, the K amide RuNK, Ru dihydride, and Ru amido species by detailed NMR analysis using 15 N-labeled PN(H)N and C(3)-Ph-substituted PN(H)N. The rate of BMK hydrogenation is significantly affected by [CH 3 OK] 0 , showing a characteristic curve with a peak followed by a pseudo-minus-first-order decay. The RuNH is easily deprotonated by CH 3 OK to generate RuNK, which is less reactive but has the same enantioface discrimination ability. Increased contribution of the slow RuNK cycle decreases the rate at higher [CH 3 OK] 0 . The RuNH-and RuNK-involved dual catalytic cycle is supported by curve-fitting analyses and K + trapping experiments. In hydrogenation of BMCK, only the RuNH cycle operates because BMCK is preferentially deprotonated over RuNH.

Origin of Stereoselectivity in FLP-Catalyzed Asymmetric Hydrogenation of Imines

“…Several intermolecular contacts, such as π–π stacking between the iminium phenyl and the borohydride C 6 F 5 substituents, or CH···π interaction between the iminium CH 3 and the borohydride phenyl groups, are noticeable in TS-2-R 1 . As shown previously for TM-catalyzed hydrogenation reactions, these types of noncovalent interactions can strongly influence the stereochemical outcome; , therefore, they may provide notable stabilization to transition state TS-2-R 1 as well. Additional HT transition states involving the c 2 form of 2 H – could be identified on the ( R ) reaction pathway ( TS-2-R 2 and TS-2-R 3 ), but they are computed to be 2–3 kcal/mol less stable than TS-2-R 1 .…”

The key role of the latent N–H group in Milstein's catalyst for ester hydrogenation

“…Kinetic studies have the potential to validate or falsify the findings from computation, as they show conclusively what species are consumed or released on the pathway from the turnover-frequency-determining intermediate (TDI) to the turnover-frequency-determining-transition state (TDTS). 15 For example, recent kinetic investigations of metal-catalyzed hydroformylation 16 and ketone hydrogenation 17 have provided deep insight into the underlying reaction mechanisms. Although catalytic ester hydrogenation and its microscopic reverse, ADC, have been studied intensively through computational methods, detailed experimental mechanistic investigations, especially kinetic studies, are scarce.…”

Highly Enantiomerically Enriched Secondary Alcohols via Epoxide Hydrogenolysis

“…A recent review by Dub summarizes some of the potential causes for the beneficial effect of metal alkoxides in Noyori-type hydrogenation catalysis . Possible effects of the metal alkoxide include catalyst activation through deprotonation of an acidic site (e.g., replacing N–H with N–K), substrate activation where a metal alkoxide cluster stabilizes a developing negative charge on substrate oxygen, and reactivation of catalysts deactivated by trace water . Further complicating the magnitude of the effect, metal alkoxides are known to aggregate into variably sized clusters in alcohol solvents, which changes the effective concentration of both the alkoxide anion and the metal cation .…”