August 2005
Notes
Chem. Pharm. Bull. 53(8) 1017—1020 (2005)
1017
Facile Deoxygenation of Dicarbonyl Compounds Using a Samarium
Diiodide–Additive System
Yasuko KAMOCHI,* Tadahiro KUDO, Toshinobu MASUDA, and Akira TAKADATE
Daiichi College of Pharmaceutical Sciences; 22–1 Tamagawa-cho, Minami-ku, Fukuoka 815–8511, Japan.
Received January 21, 2005; accepted April 2, 2005
The reduction of a- and b-dicarbonyl compounds was investigated with samarium diiodide in the presence
of additive. Diketones and ketocarboxylic acids were easily reduced at room temperature to give the mono-alco-
hols in good to excellent yield, and ketoester afforded the saturated ester as the major product in moderate yield.
These reductions containing the reductive deoxygenation can be rapidly performed under the facile and mild
conditions by this method.
Key words samarium diiodide; reductive deoxygenation; a-dicarbonyl compound; b-dicarbonyl compound; mono-ketone;
mono-alcohol
Samarium diiodide (SmI2) has been used as a versatile tem to give 1-phenylethanol in excellent yield (Run 9). The
reagent for synthetic organic chemistry due to its unique reduction of 1,2-diketoacenaphthene by this system afforded
characteristics.1—5) The single-electron donor ability of SmI2 acenaphthenol as a major product along with acenaphthylene
is strongly affected by the nature of the ligands around Sm2ꢀ. and acenaphthene (Run 14).
Generally, it can be expected to facilitate the release of an
Also, as shown in Tables 2 and 3, the reactions of ketocar-
electron from a metal ion when sufficient electrons are sup- boxylic acids and their derivatives with this system were car-
plied from ligands around the metal ion. Therefore, the re- ried out under similar conditions.
ducing ability can be greatly enhanced by the coordination of
additive to SmI2.
In the reduction reactions of a-ketocarboxylic acids and
ester, reductive deoxygenation with the SmI2–KOH system
In a previous paper,6) we reported that a variety of organic proceeded more smoothly than with the other systems. In ad-
functionalities such as carboxylic acids, esters, amides, ni- dition, the reduction of carboxyl functionality was advanced
triles, phenols and pyridines were rapidly reduced to the cor- more effectively than ester functionality with this system
responding products with the SmI2–additive system. In fact, (Table 2). This is believed to be because the single-electron
the marked effects of additives such as base,7—11) acid12) and transfer from Sm2ꢀ to substrate is easy to become cause by
water13,14) were observed in the reduction of organic com- coordination of substrate to Sm2ꢀ. Accordingly, because the
pounds with SmI2.
ketocarboxylic acid generates a carboxylate ion in the pres-
A few reducing reagents have been reported for the deoxy- ence of KOH, its coordination ability increases compared
genation of diketones, such as Zn–Hg/HCl,15,16) Zn–Hg/HI,17) with ester. Furthermore, the single-electron donor ability of
Zn/AcOH18) and LiAlH4.19) Regarding the deoxygenation of Sm2ꢀ can be greatly enhanced by the addition of a base and
a-oxygenated esters, SmI2–MeOH and SmI2–HMPA–pivalic hence the reduction of ketocarboxylic acid has been facili-
acid systems have also been described.20—22) However, little tated by this system. Actually, ketocarboxylic acids gave
has been reported on the deoxygenation of a- and b-dike- mono-alcohols in high yields (Runs 5, 6). However, in the re-
tones with SmI2. The present paper deals with the facile re- duction of ketoester, saturated ester was obtained as a main
ductive deoxygenation of a- or b-diketones, ketocarboxylic product under the same reaction conditions in moderate
acids, and their derivatives. As shown in Table 1, in order to yields (Runs 9—11).
compare the reducing abilities of SmI2–additive systems to-
Interestingly, on the reaction of a-ketonitrile, benzoyl
wards dicarbonyl compounds, we first attempted the reduc- cyanide was reduced by this system to yield benzaldehyde
tion of benzil with a variety of SmI2–additive systems (Runs with reductive elimination of the cyano group under similar
1—8). The reductive deoxygenation with SmI2 in the ab- conditions (Table 3).
sence of additive did not proceed with high efficiency (Runs
In the similar reduction of b-diketones, the result of the re-
1, 2). However, as might be expected, the same reactions of ductions was almost the same as for a-diketones. As shown
a-diketones were rapidly performed with SmI2 in the pres- in Table 4, the reductive deoxygenation of these compounds
ence of an additive such as H2O, H3PO4 or KOH. Among the also proceeded with SmI2–additive systems at room tempera-
systems tested, benzil was rapidly reduced with the ture to afford the corresponding mono-alcohols and mono-
SmI2–H2O (Run 4) or 50% KOH (Run 8) system at room ketones along with the bis-alcohols. Mono-alcohols were ob-
temperature to give 1,2-diphenylethanol, in good yield, ac- tained with the SmI2–H2O system in good to excellent yields
companied by deoxybenzoin. Because it could be performed (Runs 1, 2, 5—7).
under extremely mild conditions, the reductive deoxygena-
On the other hand, in the reaction of b-ketocarboxylic acid
tion reactions of some a-diketones were examined using the and ester, the yields of deoxygenated products were generally
SmI2–H2O system (Runs 9—14). The a-diketones tested unsatisfactory (Table 5).
were rapidly reduced to the corresponding mono-alcohols at
The deoxygenation of g-carbonyl compounds did not pro-
high yields, and the formyl group of phenylglyoxal was par- ceed using this system, and the reduction product was the
ticularly easily converted into a methyl group with this sys- bis-alcohol. For example, cyclohexane-1,4-dione was imme-
∗ To whom correspondence should be addressed. e-mail: kamochi@daiichi-cps.ac.jp
© 2005 Pharmaceutical Society of Japan