Enantioselective reduction of methyl benzoylformate

Chemical Properties

Methyl benzoylformate (MBF, C9H8O3, CAS registry No. 15206-55-0) is also called methyl 2-oxo-2-phenylacetate, which is a light yellow liquid. Its melting point is 16 oC, and flash point is 103.8 oC. It is insoluble in water and basic. It is stable under normal temperatures and pressures. Store in a cool, dry place and keep container closed when not in use. It may cause an allergic skin reaction.

Benzoyl derivatives

MBF is classified as a benzoyl derivative or a benzoyl derivative. Benzoyl derivatives are organic compounds containing an acyl moiety of benzoic acid with the formula (C6H5CO-). MBF is the methyl ester of phenylglyoxylic acid with methanol. It is a methyl ester and an alpha-ketoester. The enantioselective reduction of MBP has been investigated with different catalysts. For example, the enantioselective hydrogenation of MBF was studied under mild experimental conditions on Pt-alumina catalyst modified with MeOCD, MeOCN, MeOQN and MeOQD alkaloid derivatives in acetic acid (AcOH) and in toluene with the highest enantiomeric excess (ee) (50–80%)[1].

The Mg2+ ion-activated enantioselective reduction of MBF have been investigated at a B3LYP/6-31G* theory level, using peptide NADH models 1 rigidified with a β-lactam ring, with ee up to 90%[2].

Reduction of Methyl benzoylformate

MBF can be reduced by biotransformation with high enantioselectivity, mild reaction conditions and environmental compatibility. The asymmetric reduction of MBF with yeast cells Saccharomyces cerevisiae 21 can produce (R)-(-)-mandelic acid methyl ester, a key drug intermediate as an optical active substance, which are not only the essential building blocks for drugs such as semi-synthetic penicillins, cephalosporins, antitumor and antiobesity agents but also the versatile resolving agents in chiral resolution processes. Conversion and enantiometric excess of (R)-(-)-mandelic acid methyl ester were 99.4% and 99.9% under above optimum reduction conditions[3]. Another yeast cell Saccharomyces cerevisiae AS2.1392 can also be used for the asymmetric reduction of MBF to (R)-methyl mandelate with a yield of 85.8% and an ee of 95.4%. Furthermore, resin-based in situ product removal (ISPR) technique was applied to alleviate the substrate and product inhibition or toxicity to the whole cells[4].

As another example, transfer hydrogenation of MBF with 2-propanol has been studied on rhodium nanoparticles obtained by the reduction of rhodium(I) complexes in the presence of optically active compounds, including chiral diamine S,S-DIODMA, (4S,5S)-N4,N4,N5,N5,2,2-hexamethyl-4,5-bis-(aminomethylene)-1,3-dioxolane, quaternary diammonium salt (4S,5S)-(-)-N1,N4-dibenzyl-2,3-dihydroxy-N1,N1,N4,N4-tetramethylbutane-1,4-diammonium dichloride, and (8S,9R)-(-)-cinchonidine. Increasing the modifier to Rh ratio leads to an increase in the ee of the reaction products[5].

Fig 1. Chemical structure formula of methyl benzoylformate

References

[1]. Balazsik, K.; Bucsi, I.; Cserenyi, S.; Szoellosi, G.; Bartok, M., Methylethers of cinchona alkaloids in Pt-catalyzed hydrogenation of methyl benzoylformate and pyruvaldehyde dimethyl acetal - Part 2: Effect of stereochemical factors on the enantioselectivity. Journal of Molecular Catalysis a-Chemical 2008, 285 (1-2), 84-91.

[2]. Aizpurua, J. M.; Palomo, C.; Fratila, R. M.; Ferrón, P.; Benito, A.; Gómez-Bengoa, E.; Miranda, J. I.; Santos, J. I., Mechanistic Insights on the Magnesium(II) Ion-Activated Reduction of Methyl Benzoylformate with Chelated NADH Peptide β-Lactam Models. The Journal of Organic Chemistry 2009, 74 (17), 6691-6702.

[3]. Ou, Z.; Liu, Y.; Nan, Y. In Synthesis of (R)-(-)-mandelic acid methyl ester by asymmetric reduction of methyl benzoylformate with yeast cells, Proceedings - 2012 International Conference on Biomedical Engineering and Biotechnology, iCBEB 2012, 2012; pp 562-564.