Asymmetric reductive acetylation of ketones

The catalytic alcohol racemization with diruthenium catalyst 1 is based on the reversible transfer hydrogenation mechanism. Meanwhile, the problem of ketone formation in the DKR of secondary alcohols with 1 was identified due to the liberation of molecular hydrogen. Then, we envisioned a novel asymmetric reductive acetylation of ketones to circumvent the problem of ketone formation (Scheme 6). A key factor of this process was the selection of hydrogen donors compatible with the DKR conditions. 2,6-Dimethyl-4-heptanol, which cannot be acylated by lipases, was chosen as a proper hydrogen donor. Asymmetric reductive acetylation of ketones was also possible under 1 atm hydrogen in ethyl acetate, which acted as acyl donor and solvent. Ethanol formation from ethyl acetate did not cause critical problem, and various ketones were successfully transformed into the corresponding chiral acetates (Table 17). However, reaction time (96 h) was unsatisfactory. 

Asymmetric reductive acetylation was also applicable to acetoxyphenyl ketones. In this case the substrate itself acts as an acyl donor. For example, m-acetoxyace-tophenone was transformed to (R)-l-(3-hydroxyphenyl)ethyl acetate under 1 atm H2 in 95% yield [16] (Scheme 1.12). The pathway of this reaction is rather complex. It was confirmed that nine catalytic steps are involved two steps for ruthenium-catalyzed reductions, two steps for ruthenium-catalyzed racemizations, two steps... 

Very recently it has been shown that electrode surfaces can be chemically modified.13 Although no useful reactions have come from this work, it has been shown that organic molecules can be covalently attached to electrode surfaces and that these modified surfaces impart selectivity to electrochemical reactions which is not otherwise available. Attempts have also been made to increase the selectivity of electrochemical reactions by adsorbing material on the electrode surface. In particular if chiral alkaloids are adsorbed on mercury, it Is then possible to perform the asymmetric reduction of prochiral ketones tc chiral alcohols. An optical yield of 54% has, for example, been reported for the reduction of 4-acetyl pyridine in aqueous-ethanol using strychnine as the catalytic, chiral reagent.11 ... 

Preparation. [(i )-a-(2-Naphthyl)aminomethyl]ferrocene was prepared in three steps from ferrocenyl 2-naphthyl ketone featuring an asymmetric CBS reduction with >99% ee (eq 1). After protection of the secondary hydroxyl group with an acetyl group, a nucleophilic displacement of the acetoxy group with an amino group proceeded with retention of stereochemistry. A range of different variations of [(i )-a-(2-naphthyl)aminomethyl]ferro-cene could be prepared using this sequence with similar efficiency. 

Examples of this kind of enantiomorphic or chiral selectivity are now being found in organic synthesis. Asymmetric synthesis, for example, has been demonstrated with stereo-controlled Michael addition in the synthesis of beta-lactams using chiral catalysts, where an acyl ligand such as acetyl is bound to cyclo-pentadiene carbonyl triphenylphosphine. Essentially complete enantiomorphic selectivity has been achieved in this Michael addition synthesis. Another case is enantio-morhic ketone reduction in ethylbenzene reduction in the ethylation of benzaldehyde. Using chiral catalysts, 97% selectivity has been achieved. Closely related research involves the making of catalytic antibodies and hybrid enzymes. ... 

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