Asymmetric reductive acetylation

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 process was also applicable to acetox-yaryl ketones. For example, m-acetoxyacetophenone 10 was transformed to... 

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... 

Asymmetric reductive acetylation of benzylic ketoximes with CAL-B and Pd/AIO(OH). 

A range of chiral alkaloids have been screened for the asymmetric reduction of 2- and 4-acetyl pyridine [41] and results are given in Table 10.5. Brucine and strychnine give the highest enantiomeric excess in the pyridinylethanols produced. Reduction of 3-acetylpyridine however affords no optically active alcohol under all conditions employed. A further effect of the added alkaloid is to raise the yield of secondary alcohol at the expense of the pinacols relative to reactions where no alkaloid is present. The high enantiomeric excess found during reduction of 4 ... 

Pyrrolopyridine derivatives, such as compound 144, in the presence of Mg salts such as magnesium perchlorate, serve as chiral and nonchiral NADH models in the reduction of organic nitro compounds <1996JHC1211>. Similar derivatives, such as compound 145, serve as NADH models in the asymmetric reduction of methyl benzoylformate and A -acetyl enamines <1997TA3309>. 

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 ... 

In 2001, Tungler and coworkers described the diastereoselective hydrogenation of N (1 methylpyrrole 2 acetyl) (S) proline methyl ester (32) using the Rh/C as cata lyst [40]. By introducing (S) proline moiety as chiral auxiliary, high asymmetric induction was obtained. When 32 was subjected to 5% Rh/C catalyst in methanol with 20 bar H2, the reduced product 33 was obtained with full conversion and 95% de. This substrate induced asymmetric reduction and was effective only to (2 pyrrolyl) acetic acid derivatives (Scheme 10.30). 

Scheme 7.13. (a) Morrison s asymmetric reduction of P-methyl cinnamic acid [116]. (b) Kagan s asymmetric reduction of Al-acetyl dehydrophenylalanine and the debut of the DIOP ligand [117]. 

The aldehyde 218 possessing 2,6-frans-tetrahydropyran, was synthesized as shown in Scheme 48. /3-Keto ester 220 was reduced by Noyori hydrogenation [97] to give 6-hydroxy ester 221 in 94% ee, which was converted into iodide 222. Asymmetric alkylation using Myers chiral auxiliary [98] with 222, followed by acid treatment, furnished 5-lactone 223 with high stereoselectivity. Reductive acetylation, axial allylation by the Hosomi-Sakurai reaction, and ozonolysis completed the synthesis of 218. 

When a racemic substance is hydrogenated or when the reduction leads to the production of centers of asymmetry, the phytochemical reduction will take at first a completely or partially asymmetric course. Examples of such asymmetric reactions are the conversions of pure racemic valeraldehyde, acetaldol, furoin and furil, diacetyl and acetyl-methylcarbinol to optically active alcohols. Occasionally meso forms also arise, as for example in the case off glycols (p. 84). The reasons for the stereochemical specificity of these reactions have not been clarified. This type of phenomenon has frequently been observed in the related intramolecular dismutation of keto aldehydes, especially if enzyme materials of differing origins are used. 

Miller and his co-workers60) reported surprisingly high optical yields, close to 50 %, in the reduction of 2-acetylpyridine in the presence of strychnine. They also prepared chemically modified electrodes with optically active amino acids and attempted asymmetric induction in both reduction and oxidation61 . The best optical yield, only 14.5 %, seemed to be obtained in the reduction of 4-acetyl-pyridine on a graphite cathode modified with (S)-phenylalanine methyl ester. 

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