Reduction of 1,2-dicarbonyl compounds mediated by the combination of phosphine and lewis acid

Article abstract of DOI:10.1055/s-2004-825581

The combination of Ph₃P/AlBr₃ effectively promoted the reduction of several 1,2-dicarbonyl compounds in the presence of water (1.0 equiv) and the corresponding α-hydroxy carbonyl compounds were obtained in good yields.

Full text of DOI:10.1055/s-2004-825581

LETTER
1267
Reduction of 1,2-Dicarbonyl Compounds Mediated by the Combination of
Phosphine and Lewis Acid
Reduction of
1
a
,2-Dicarbo
t
nyl Co
o
w
it
s
h Phosphi
h
ne and Lewi
i
s
A
cid Kikuchi, Yukihiko Hashimoto*
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656,
Japan
Fax +81(3)58417281; E-mail: hashimoto@chiral.t.u-tokyo.ac.jp
Received 3 February 2004
Table 1 Reduction of Benzil to Benzoin under Several Conditionsa,b
Abstract: The combination of Ph3P/AlBr3 effectively promoted the
reduction of several 1,2-dicarbonyl compounds in the presence of
water (1.0 equiv) and the corresponding a-hydroxy carbonyl com-
pounds were obtained in good yields.
O
O
Ph3P/Lewis acid
Ph
Ph
Ph
Ph
Conditions, r.t., 24 h
Key words: phosphorus, phosphine, Lewis acid, reduction, 1,2-di-
O
OH
carbonyl compounds
3
ClCH2CH2Cl CH3CN
CH2Cl2
Water (1.0 equiv)
CH3CN CH2Cl2
Until now, various procedures have been developed for
the reduction of 1,2-dicarbonyl compounds to give a-hy-
droxy carbonyl compounds in good yields without over-
reduction to diols or mono-ketones.1 For example, it was
reported that the reduction of benzil was effectively medi-
ated by Zn,1a TiI4,1b and VCl2,1c among others.
AlBr3
SiBr4
SnBr4
BBr3
55
50
56
82
86
89
36
60
76
28
29
86
98
66
60
80
95
–
–
82
On the other hand, we have recently examined composite
reagents, combinations of phosphine and Lewis acid,
which showed interesting and characteristic reducing
ability. We have already reported that the reduction of
various a-bromocarboxylic acid derivatives proceeded in
good yield under mild conditions,2 and that the Refor-
matsky-type reaction of a-bromocarbonyl compounds
was promoted by this combination to give the desired ad-
ducts in good yields with high diastereoselectivity.3
a Molar ratio of 3:Ph3P:Lewis acid = 1.0:1.2:1.4.
b Isolated yield (%).
Initially, the reduction of benzil was examined by using
the combinations of Ph3P and Lewis acid in ClCH2CH2Cl
at room temperature. Among many Lewis acids exam-
ined, chlorides and triflates, such as AlCl3, TiCl4,
Sc(OTf)3, Yb(OTf)3 and SnCl4, did not promote the reac-
tion. However, the reaction proceeded smoothly with bro-
mide salts as the Lewis acid (55% yield using AlBr3).
For the purpose of extending the applicability of these
composite reagents, we have recently applied them to
various types of reductions. In this communication, we
show that the reduction of 1,2-dicarbonyl compounds was
effectively mediated by the combination of phosphine and
a Lewis acid.
This result could be explained as follows: as shown in
Scheme 1, this reduction is considered to progress
through the enediolate 2 formed by the attack of Ph3P on
the substituent X in 1, which originates from an anion part
MXn
O
MXn-1
O
MXn-2
O
O
O
O
OH
H2O
O
R2
OH
R2
R1
R1
R1
R1
R1
X
R2
R2
R2
O
Ph3P
M = Al, B, etc
1
2
Ph3PX2
Scheme 1
SYNLETT 2004, No. 7, pp 1267–1269
0
3.
0
6.
2
0
0
4
Advanced online publication: 10.05.2004
DOI: 10.1055/s-2004-825581; Art ID: U03204ST
© Georg Thieme Verlag Stuttgart · New York

1268
S. Kikuchi, Y. Hashimoto
LETTER
of the Lewis acid. That is to say, it is essential that the in- known that the yield is improved by adding 1.0 equivalent
termediate 1 should be smoothly formed and the attack of of water.2 In this reaction, a similar effect was observed
Ph3P should occur easily. Therefore the bromide salt for some cases.
seems to be the most suitable Lewis acid.
Under the optimized conditions, the reduction of several
Next, we screened the reaction conditions, such as sol- 1,2-dicarbonyl compounds was carried out. The results
vents and additives, by using a combination of several are summarized in Table 2.6
bromide salts and Ph3P.4 The results are summarized in
As can been seen from Table 2, the reduction of diketones
Table 1.
proceeded smoothly and a-hydroxy ketones were ob-
Consequently, it was found that various solvents and tained in good yields except for dialkyl diketone (entries
Lewis acids could be used for this reaction. Among them, 1–5). Furthermore, the reduction of phenylglyoxal (entry
under several conditions, such as AlBr3 in CH3CN with 6) was found to proceed selectively at the aldehyde in
water, SiBr4 in anhydrous CH3CN, and BBr3 in anhydrous moderate yield. In the case of thioester derived from
CH2Cl2, the reduction proceeded smoothly. The combina- phenylglyoxylic acid, the thioester moiety was selectively
tion of Ph3P/AlBr3 in CH3CN in the presence of water (1.0 reduced to give 2-hydroxyacetophenone in good yield
equiv) gave the highest yield (98%).5 In the reduction of (entry 7). This selectivity was different from the result of
the a-bromocarbonyl compounds with GeCl4/Ph3P, it is the reduction of methyl phenylglyoxylate using TiI4,
Table 2 The Reduction of Various 1,2-Dicarbonyl Compounds by Ph3P/AlBr3 Combination in CH3CN with Water.a
O
O
OH
Ph3P/AlBr3, H2O
CH3CN, r.t., 24 h
R2
R2
OH
R2
R1
R1
R1
O
O
4
Entry
Substrate
Yield (%) of Productb
O
O
Ar
Ar
Ar
Ar
OH
O
1
2
3
Ar = Ph, 98%
Ar = p-MeC6H4, Quant.
Ar = p-ClC6H4, 95%
4c
O
OH
O
Me
Ph
Me
Me
Ph
Ph
11%d
OH
55%d
O
O
5
O
O
Ph
Ph
Ph
Ph
O
OH
30%
6
O
OH
H
H
O
Ph
Ph
OH
Ph
O
O
OH
60%
0%
7e
O
SPh
O
SPh
Ph
Ph
OH
Ph
O
O
78%
0%
a Molar ratio of 4:Ph3P:AlBr3:H2O = 1.0:1.2:1.4:1.1.
b Isolated yield.
c Quenched at 0 °C.
d Determined by 1H NMR at 300 MHz.
e Molar ratio of 4:Ph3P:AlBr3:H2O = 1.0:2.0:2.3:1.0.
Synlett 2004, No. 7, 1267–1269 © Thieme Stuttgart · New York

LETTER
Reduction of 1,2-Dicarbonyl Compounds with Phosphine and Lewis Acid
1269
which gave mandelic acid methyl ester via reduction of
the keto functional group.1c
References
(1) (a) Radha Rani, B.; Ubukata, M.; Osada, H. Bull. Chem. Soc.
Jpn. 1995, 68, 282. (b) Hayakawa, Y.; Sahara, T.; Shimizu,
M. Tetrahedron Lett. 2000, 41, 7939. (c) Ho, T.-L.; Olah,
G. A. Synthesis 1976, 815. (d) Nakamura, K.; Kondo, S.;
Kawai, Y.; Hida, K.; Kitano, K.; Ohno, A. Tetrahedron:
Asymmetry 1996, 7, 409. (e) Mashima, K.; Kusano, K.;
Sato, N.; Matumura, Y.; Nozaki, K.; Kumobayashi, H.;
Sayo, N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.; Takaya, H.
J. Org. Chem. 1994, 59, 3064. (f) Suzuki, H.; Manabe, H.;
Enokiya, R.; Hanazaki, Y. Chem. Lett. 1986, 1339.
(2) Kagoshima, H.; Hashimoto, Y.; Oguro, D.; Kutsuna, T.;
Saigo, K. Tetrahedron Lett. 1998, 39, 1203.
(3) (a) Kagoshima, H.; Hashimoto, Y.; Saigo, K. Tetrahedron
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(4) Other phosphines, such as n-Bu3P, (o-tolyl)3P, were also
examined, but Ph3P gave the best result.
In summary, these composite reagents, i.e. the combina-
tion of Ph3P and Lewis acid, is an excellent promoter of
the reduction of 1,2-dicarbonyl compounds to give a-hy-
droxy carbonyl compounds. It is also noted that the reduc-
tion of keto-thioester by this combination proceeded
selectively at the thioester function to give the keto-alco-
hol. Moreover, several bromide-Lewis acids can be used
in appropriate solvents and the experimental operation is
very simple, making this method very useful in organic
syntheses.
Acknowledgment
This work was financially supported by a Grant-in-Aid for Scienti-
fic Research (C) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
(5) Although the generation of HBr was assumed under these
conditions, it seemed that it was not involved in the reaction
because the reduction did not proceed when Ph3P and HBr
were used instead of Ph3P and AlBr3.
(6) Typical Procedure for Reduction of Benzil (Table 2,
Entry 1): Under an argon atmosphere to a solution of AlBr3
(183.2 mg, 0.69 mmol) and benzil (103.6 mg, 0.49 mmol) in
CH3CN (1 mL), which was stirred for 15 min, was added
water (9 mL, 0.55 mmol). After 1 h, a solution of Ph3P (180.5
mg, 0.69 mmol) in CH3CN (2 mL) was added and stirred for
24 h. The reaction was quenched with 1 N aq HCl and the
mixture was extracted with Et2O (5 × 10 mL). The combined
organic layer was dried over MgSO4. This organic layer was
filtered and evaporated under reduced pressure, and then the
crude product was purified by preparative TLC (SiO2,
CH2Cl2) to give benzoin (101.5 mg, 98% yield).
Synlett 2004, No. 7, 1267–1269 © Thieme Stuttgart · New York