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To ensure the quasi‐irreversibility of the oxidation of alcohols coupled with the reduction of ketones in a hydrogen‐transfer (HT) fashion, stoichiometric amounts of α‐halo carbonyl compounds have been employed as hydrogen acceptors. The reason that these substrates lead to quasi‐quantitative conversions has been tacitly attributed to both thermodynamic and kinetic effects. To provide a clear rationale for this behavior, we investigate herein the redox equilibrium of a selected series of ketones and 2‐propanol by undertaking a study that combines experimental and theoretical approaches. First, the activity of the (R)‐specific alcohol dehydrogenase from Lactobacillus brevis(LBADH) with these substrates was studied. The docking of acetophenone/(R)‐1‐phenyethanol and α‐chloroacetophenone/(S)‐2‐chloro‐1‐phenylethanol in the active site of the enzyme confirms that there seems to be no structural reason for the lack of reactivity of halohydrins. This assumption is confirmed by the fact that the corresponding aluminum‐catalyzed Meerwein–Ponndorf–Verley–Oppenauer (MPVO) reactions afford similar conversions to those obtained with LBADH, showing that the observed reactivity is independent of the catalyst employed. While the initial rates of the enzymatic reductions and the IR ν(CO) values contradict the general belief that electron‐withdrawing groups increase the electrophilicity of the carbonyl group, the calculated ΔGvalues of the isodesmic redox transformations of these series of ketones/alcohols with 2‐propanol/acetone support the thermodynamic control of the reaction. As a result, a general method to predict the degree of conversion obtained in the HT‐reduction process of a given ketone based on the IR absorption band of the carbonyl group is proposed, and a strategy to achieve the HT oxidation of halohydrins is also shown.

The kinetic resolution of (±)‐1‐phenylbutan‐1‐ol [(±)‐1] by means of CALB‐catalyzed aminolysis of its acetyl derivative [(±)‐2] using (±)‐1‐phenylethanamine [(±)‐3] as nucleophile is a slower but more enantioselective process (E= 50) than the corresponding CALB‐catalyzed transesterification of (±)‐1with vinyl acetate (E= 19). The use of triethylamine and acetanilide as additives in the transesterification of (±)‐1enhanced the enantiomeric ratio (E= 43 and 38, respectively), thus showing that both the basic character of the amine as well as its structural nature could be responsible for the enantioselectivity differences observed between the transesterification and aminolysis reactions. We have also carried out the aminolysis of (±)‐2using different chiral and non‐chiral amines. Enantiomeric ratio values varied significantly with the amine employed, but the enzyme always remained more selective towards the R‐enantiomer of the substrate. Among all the amines tested, (±)‐1‐phenylpropan‐1‐amine [(±)‐5] was the nucleophile of choice. Analysis of the conversion values for each enantiomer of (±)‐2showed that the selectivity differences exhibited by the lipase in the aminolysis reactions were due to the different stabilization of the fast‐reacting enantiomer of the substrate [(R)‐2] during the catalytic process. The CALB behavior in these reactions could be explained on the basis of substrate imprinting effects, which were corroborated by means of enzyme recycling experiments. Finally, a solvent screening allowed the kinetic resolution of this alcohol for synthetic purposes.

Enzymatic aminolysis of racemic secondary alcohol ester derivatives with racemic amines leads to the resolution, in one reaction, of the alcohol and the amine with very high enantioselectivity.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.