Chemistry Letters 2002
1081
2b : n = 2
2c : n = 3
2d : n = 5
Table 2. Optimization of the reaction conditions for desymmetriza-
tion of 2a using 7 as the catalysta
OH
OH
OH
OH
(CH )
2 n
2e
Entry
Solvent
Time/d
Yield/%b
% eec,d
In conclusion, we were able to demonstrate that enantio-
topos-selective aerobic oxidation of meso-diols could be achieved
by using (nitrosyl)(salen)ruthenium complex as the catalyst under
photo-irradiation, though there is some room for improvement in
enantioselectivity. Further study on aerobic asymmetric oxida-
tion of meso-diols is in progress.
1
2
benzene
THF
1
1
64
21
16
77
29
33
35
54
85
32
65
55
52
51
58
53
55
65
67
59
62
67
3
acetone
AcOEt
toluene
PhCl
1
4
1
5
1
6
1
7
CH2Cl2
CHCl3
(CH2Cl)2
(CHCl2)2
CHCl3
1
8
1
References and Notes
9
1
1
a) G. Fantin and P. Pedrini, in ‘‘Asymmetric Oxidation Reactions,’’
ed. by T. Katsuki, Oxford University Press, Oxford (2001), pp 200–
214. b) J. B. Jones, in ‘‘Asymmetric Synthesis,’’ ed. by J. D.
Morrison, Academic Press, New York (1984), Vol. 5, pp 309–344.
a) Y. Ishii, K. Suzuki, T. Ikariya, M. Saburi, and S. Yoshikawa, J.
Org. Chem., 51, 2822 (1986). b) Y. Ishii, K. Osakada, T. Ikariya,
and M. Saburi, Chem. Lett., 1982, 1179.
Asymmetric Oppenauer oxidation-like desymmetrization of meso-
diols (up to 50% ee) has recently been reported: M. Ito, A. Osaku,
and T. Ikariya, The 84th Annual Meeting of the Chemical Society of
Japan, Tokyo, March 2002, Abstr., No. 3 G4–14.
10
11
1
2.7
aReactions were carried out under irradiation using a halogen lamp as
the light source. bIsolated yield of lactol 3a. cDetermined by GLC
analysis using optically active column (SUPELCO BETA-DEX-225)
after its conversion to the corresponding lactone. dThe absolute
configuration of the product was 1R, 6S.
2
3
We next examined the effect of solvent on enantioselectivity
(Table 2). Although the solvent effect was small, the reactions in
halocarbons (entries 7–10) generally showed good enantioselec-
tivity, and the best result was obtained when chloroform was used
as the solvent (entry 8). The reaction was slow but elongation of
the reaction time increased the chemical yield without changing
enantioselectivity (entry 11).
4
5
K. Masutani, T. Uchida, R. Irie, and T. Katsuki, Tetrahedron Lett.,
41, 5119 (2000).
Enantiomer-differentiating aerobic oxidation of racemic alcohols
has recently been reported: a) D. R. Jensen, J. S. Pugsley, and M. S.
Sigman, J. Am. Chem. Soc., 123, 7475 (2001). b) E. M. Ferreira and
B. M. Stoltz, J. Am. Chem. Soc., 123, 7725 (2001).
Desymmetrization of a series of meso-1,2-di(hydroxy-
methyl)cycloalkanes (2b–d) was also examined under the
optimized conditions (Table 3). The ring size of diols affects
enantioselectivity of the reactions to a small extent (entries 1–3).
Oxidation of meso-4,5-di(hydroxymethyl)cyclohexene 2e ex-
hibited a similar level of enantioselectivity (entry 4).10 It is
noteworthy that no epimerization was observed in these
reactions.11
6
7
8
A. Miyata, M. Murakami, R. Irie, and T. Katsuki, Tetrahedron Lett.,
42, 7067 (2001).
A. Miyata, M. Furukawa, R. Irie, and T. Katsuki, Tetrahedron Lett.,
43, 3481 (2002).
(R; R)-1,2-Diamino-1,2-dimethylcyclohexane was prepared ac-
cording to the reported procedure: W. Zhang and E. N. Jacobsen,
Tetrahedron Lett., 32, 1711 (1991).
a) I. J. Jakovac, H. B. Goodbrand, K. P. Lok, and J. B. Jones, J. Am.
Chem. Soc., 104, 4659 (1982). b) I. J. Jakovac, G. Ng, K. P. Lok, and
J. B. Jones, J. Chem. Soc., Chem. Commun., 1980, 515. c) H.-J.
Gais, K. L. Lukas, W. A. Ball, S. Braun, and H. J. Lindner, Liebigs
Ann. Chem., 1986, 687.
9
O
7 (2.0 mol%), air
hν, rt, CHCl3
PDC, MS4A
CH2Cl2
(CH )
3
2
O
2 n
10 Typical experimental procedure is exemplified by the oxidative
desymmetrization of 2a: meso-diol 2a (14.4 mg, 0.1 mmol) and
(ON)Ru(salen) 7 (2.0 mg, 2.0 mol%) were dissolved in anhydrous
chloroform (0.5 mL). The solution was stirred under irradiation
with a halogen lamp in air for 2.7 days at room temperature. The
mixture was directly chromatographed on silica gel (hexane/ethyl
acetate = 1/1) to give lactol 3a (9.2 mg, 65%). To a suspension of
4
Table 3. Catalytic oxidative desymmetrization of various meso-diols
2 using 7 as the catalysta
Entry
Substrate
Time/d
Yield/%b
% eec
Confignd
1
2
3
4
2b
2c
2d
2e
2
3
2
3
49
57
64
66
59
65
63
66
1R, 4Se
1R, 5Sf
ꢀ
lactol 3a and 4 A molecular sieves (100 mg) in anhydrous
dichloromethane (0.5 mL) was added pyridinium dichromate
(49 mg, 0.13 mmol). The mixture was stirred for 6 h at room
temperature, diluted with hexane/ethyl acetate (4/1) and filtered
through a pad of silica gel. The filtrate was concentrated under
reduced pressure. The enantiomeric excess of the resulting lactone
was determined by GLC analysis using optically active column
(SUPELCO BETA-DEX-225).
g
—
1R, 6Sh
aReactions were carried out under irradiation using a halogen lamp as
the light source. bIsolated yield of lactol 3. cDetermined by GLC
analysis using optically active column (SUPELCO BETA-DEX-225)
after its conversion to the corresponding lactone. dThe absolute
configuration of the product was determined by comparison of the
specific rotation after its conversion to the corresponding lactone.
eRef. 9b. fRef. 9b. gThe absolute configuration has not been
determined. hRef. 9c.
11 All the lactones obtained in these reactions have the corresponding
cis-bicyclo ring structures. The configuration of the lactone derived
from 2d was proven to be cis by the chemical correlation: LAH
reduction of the lactone gave meso-diol 2d.