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A Multilateral Mechanistic Study into Asymmetric Transfer Hydrogenation in Water
Author(s) -
Wu Xiaofeng,
Liu Jianke,
Di Tommaso Devis,
Iggo Jonathan A.,
Catlow C. Richard A.,
Bacsa John,
Xiao Jianliang
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800559
Subject(s) - chemistry , acetophenone , transfer hydrogenation , catalysis , ruthenium , hydride , ketone , catalytic cycle , medicinal chemistry , aqueous solution , hydrogen , organic chemistry
The mechanism of aqueous‐phase asymmetric transfer hydrogenation (ATH) of acetophenone (acp) with HCOONa catalyzed by Ru‐TsDPEN has been investigated by stoichiometric reactions, NMR probing, kinetic and isotope effect measurements, DFT modeling, and X‐ray structure analysis. The chloride [RuCl(TsDPEN)( p ‐cymene)] ( 1 ), hydride [RuH(TsDPEN)( p ‐cymene)] ( 3 ), and the 16‐electorn species [Ru(TsDPEN‐H)( p ‐cymene)] ( 4 ) were shown to be involved in the aqueous ATH, with 1 being the precatalyst, and 3 as the active catalyst detectable by NMR in both stoichiometric and catalytic reactions. The formato complex [Ru(OCOH)(TsDPEN)( p ‐cymene)] ( 2 ) was not observed; its existence, however, was demonstrated by its reversible decarboxylation to form 3 . Both 1 and 3 were protonated under acidic conditions, leading to ring opening of the TsDPEN ligand. 4 reacted with water, affording a hydroxyl species. In a homogeneous DMF/H 2 O solvent, the ATH was found to be first order in the concentration of catalyst and acp, and inhibited by CO 2 . In conjunction with the NMR results, this suggests that hydrogen transfer to ketone is the rate‐determining step. The addition of water stabilized the ruthenium catalyst and accelerated the ATH reaction; it does so by participating in the catalytic cycle. DFT calculations revealed that water hydrogen bonds to the ketone oxygen at the transition state of hydrogen transfer, lowering the energy barrier by about 4 kcal mol −1 . The calculations also suggested that the hydrogen transfer is more step‐wise in nature rather than concerted. This is supported to some degree by the kinetic isotope effects, which were obscured by extensive H/D scrambling.