Mechanistic aspects of the rhodium-catalyzed enantioselective transfer hydrogenation of α,β-Unsaturated carboxylic acids using formic acid/triethylamine (5:2) as the hydrogen source

Article abstract of DOI:10.1021/ja00054a021

The mechanism of the rhodium-catalyzed enantioselective transfer hydrogenation of methylenebutanedioic acid (itaconic acid) (1) and related α,β-unsaturated carboxylic acids using formic acid/triethylamine (5:2) as the hydrogen source is investigated. Kinetic studies using ¹H 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 ¹H and ¹³C{¹H,²H} 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 (β-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 α-acetamidocinnamate, n = 1, 12) of the catalytic cycle of hydrogenation using gaseous hydrogen is followed by ³¹P 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.