2494
J . Org. Chem. 1997, 62, 2494-2499
Asym m etr ic Electr or ed u ction of Keton e a n d Ald eh yd e Der iva tives
to th e Cor r esp on d in g Alcoh ols Usin g Alcoh ol Deh yd r ogen a se a s a n
Electr oca ta lyst
Ruo Yuan, Shozo Watanabe, Susumu Kuwabata, and Hiroshi Yoneyama*
Department of Applied Chemistry, Faculty of Engineering, Osaka University,
Yamada-oka 2-1, Suita, Osaka 565, J apan
Received November 4, 1996X
Asymmetric electroreduction of ketone and aldehyde derivatives was examined for two electrochemi-
cal reduction systems using alcohol dehydrogenase (ADH) as an electrocatalyst. The reaction system
A is concerned with reduction of substrates catalyzed by ADH coupled with regeneration of cofactors
by another enzyme with assistance of methyl viologen as an electron mediator, and the reaction
system B is concerned with the use of ADH as the sole enzyme which catalyzes both reduction of
substrates and regeneration of cofactors. In the latter case, a redox couple of phenethyl alcohol/
acetophenone is used as an electron mediator to induce the reaction. The electrolysis using the
system A allowed asymmetric reduction of acetophenone, propiophenone, phenoxy-2-propanone,
pyruvic acid, and 2-phenylpropionaldehyde to the corresponding optically active alcohols with the
enantiomer excesses (ee) close to 100% and the current efficiencies larger than 92%, and the turnover
number of the cofactor higher than 50 was obtained for electrochemical reduction of phenoxy-2-
propanone for 30 h. The reaction system B gave 100% ee for reduction of propiophenone, phenoxy-
2-propanone, and pyruvic acid. However, the amount of products obtained was very small for
reduction of benzoylformic acid, and a low enantiomer excess was obtained for reduction of
phenylpropionaldehyde. Discussion is made focusing on what substrates are suitable for asymmetric
reduction induced by the reaction system B.
In tr od u ction
tigate mechanisms and kinetics of the enzymatic
reactions.26-29 We have developed some kinds of elec-
trochemical reaction systems using enzymes as electro-
catalysts, such as reductive fixation of carbon dioxide into
organic molecules such as R-oxoglutaric acid30 and pyru-
vic acid31 and electrochemical reduction of carbon dioxide
to methanol.32,33 Furthermore, attempts have been made
to use alcohol dehydrogenase (ADH), which is known as
a stable enzyme, as an electrocatalyst to induce electro-
chemical conversion of ketone and aldehyde derivatives
to the corresponding alcohols.34,35 Recently, synthesis of
chiral compounds is gaining popularity, and electrochemi-
Enzymes catalyze almost all in-vivo reactions with
extremely high selectivity. Many kinds of enzymes are
commercially available nowadays, and their utilization
as catalysts for in-vitro reactions has attracted consider-
able attention in relation to practical organic syntheses.1-9
In the field of electrochemistry, high selectivity that
enzymes possess has been widely utilized in electroor-
ganic syntheses10-15 and amperometric biosensors.16-25
The electrochemical techniques are also useful to inves-
* Corresponding author. Phone: +81-6-879-7372. Fax: +81-6-877-
6802. E-mail: yoneyama@ap.chem.eng.osaka-u.ac.jp.
X Abstract published in Advance ACS Abstracts, March 15, 1997.
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S0022-3263(96)02057-9 CCC: $14.00 © 1997 American Chemical Society