MECHANISTIC ASPECTS OF THE RHODIUM-CATALYZED ENANTIOSELECTIVE TRANSFER HYDROGENATION OF ALPHA,BETA-UNSATURATED CARBOXYLIC-ACIDS USING FORMIC-ACID TRIETHYLAMINE (5-2) AS THE HYDROGEN SOURCE

The mechanism of the rhodium-catalyzed enantioselective transfer hydrogenation of methylenebutanedioic acid (itaconic acid) (1) and related alpha,beta-unsaturated carboxylic acids using formic acid/triethylamine (5:2) as the hydrogen source is investigated. Kinetic studies using H-1 NMR spectroscopy are presented. Formic acid decomposition is shown to be the rate-limiting step with 1 as the substrate, while hydrogen transfer turns out to be rate determining in the case of (E)-(phenylmethylene)butanedioic acid ((E)-phenylitaconic acid) (3). Furthermore, extensive use is made of deuterium labeling and the analysis of part-deuterated products by H-1 and C-13{H-1,H-2} NMR spectroscopy. Firstly it is demonstrated that transfer deuteration of (E)-phenylitaconic acid (3) using DCO2D as the deuterium source leads to (2R*,1'S*)-2-deuterio-2-(1'-deuteriophenylmethyl)butanedioic acid (9d) as the only isotopomer. The same isotopomer is obtained using gaseous D2 under otherwise identical conditions. Use of HCO2D or DCO2H leads to a mixture of d0, d1, and d2 isotopomers 9a-d. Further information is obtained from the transfer hydrogenation of (RS)-, (R)-, and (S)-2-methylene-3-methylbutanedioic acid (beta-methylitaconic acid) (4a) with the asymmetric in-situ catalyst 8 consisting of [Rh(norbornadiene)Cl]2 and (2S,4S)-1-(tert-butoxycarbonyl)-4-(diphenylphosphino)-2-((diphenylphosphino)methyl)pyrrolidine (bppm). The pure enantiomers react at rates differing only by a factor of 2, but kinetic resolution of the racemate is efficient with a selectivity factor of 18. Additionally, the reaction of HCO2NH4 or HCO2K with intermediates [Rh(dppe)L(n)]+ (dppe = 1,2-bis(diphenylphosphino)ethane; L = MeOH, n = 2, 11; L = methyl alpha-acetamidocinnamate, n = 1, 12) of the catalytic cycle of hydrogenation using gaseous hydrogen is followed by P-31 NMR spectroscopy at variable temperature. No indication of a formate coordination to rhodium is observed in these experiments. Taken together, these results indicate that the mechanism of rhodium-catalyzed transfer hydrogenation with formic acid/triethylamine as the hydrogen source most likely involves decarboxylation of a transient formate species to form hydridic complexes of rhodium, in which the Rh-H entity has a long lifetime relative to hydrogen transfer to the substrate.