Ketone–Alcohol Hydrogen‐Transfer Equilibria: Is the Biooxidation of Halohydrins Blocked?

Abstract

Abstract:In order to ensure the quasiirreversibility of the oxidation of alcohols coupled with the reduction of ketones in a hydrogen transfer (HT) fashion, stoichiometric amounts of α-halo carbonyl compounds as hydrogen acceptors have been employed. The reason why these substrates lead to quasi-quantitative conversions has been tacitly attributed to both thermodynamic and kinetic effects. In order to provide a clear rationale for this behavior, we study here the redox equilibrium of a selected series of ketones and 2-propanol by undertaking an approach that combines experimental and theoretical elements.

Imidazolium-Based Ionic Liquids as Non-conventional Media for Alcohol Dehydrogenase-Catalysed Reactions

“…Because these ILs did not act as an appropriate hydrogen donor/acceptor with ADHs due to possible destabilizing interactions with the enzyme, a hydrogen transfer reaction with the aluminium tert-butoxide catalyst Al(O t Bu) 3 was envisaged (Scheme 4). Previous results with this catalyst have shown that when using 2-propanol for the reduction of ketones (Scheme 4a), or acetone for the oxidation of secondary alcohols, similar conversions to that observed with LBADH and ADH-A as biocatalysts were achieved [47]. Hence, whereas the reduction of 6a to 6b using 2-propanol as co-substrate with the aluminium catalyst afforded 86% of conversion, in the same reaction conditions with IL 1 only 7% of conversion was achieved (Scheme 4b).…”

Access to Enantiopure α‐Alkyl‐β‐hydroxy Esters through Dynamic Kinetic Resolutions Employing Purified/Overexpressed Alcohol Dehydrogenases

“…Thus, we have observed that carbonyl groups presenting an electron-withdrawing moiety at α-position can be quasi-irreversibly reduced by ADHs. [23,27,28] This effect has also been observed in the case of bioreductions of 1,2-and 1,3-diketones, probably due to the fact that an intramolecular H-bond is formed between the formed alcohol moiety and the remaining carbonyl group, hampering their oxidation reaction. [29] With this in mind, we envisaged that bioreductions of these β-ketoester derivatives could be highly favoured due to the formation of an intramolecular H-bond affording a stabilised 6-member ring (Figure 2), and therefore a small excess of 2-propanol could be used to achieve quantitative conversions of the corresponding β-hydroxyesters.…”

“…Since these transformations mainly rely on the thermodynamic equilibrium between the redox pairs of substrate and cosubstrate, [27] depending on the chemical structure of compounds reduced/oxidised, the reaction equilibrium will be easily (or not) displaced into the final products. Thus, we have observed that carbonyl groups presenting an electron-withdrawing moiety at α-position can be quasi-irreversibly reduced by ADHs.…”

Biocatalyzed synthesis of both enantiopure fluoromisonidazole antipodes

“…Due to the high difficulty to oxidize halohydrins, 14 it was envisioned the employment of a potent oxidant such as Jones' reagent. Thus, following a typical procedure, 15 using a mixture of acetone/water (40:1 v v -1 ) at 0ºC afforded, by TLC, the desired compound, but when the solvent was evaporated under vacuum to obtain 10, the high volatility of this ketone avoided its adequate isolation.…”