An efficient enantioselective preparation of (S,S)-1,2-bis(1-hydroxyalkyl)benzene

Article abstract of DOI:10.1246/cl.2001.1110

(S,S)-1,2-Bis(1-hydroxyalkyl)benzenes were obtained in >99% ee's with high diastereoselectivity by the enantioselective addition of dialkylzinc to (S)-2-[1-(4-methoxybenzyloxy)alkyl]-benzaldehyde (86% ee) in the presence of a catalytic amount of (S)-2-(4-

Full text of DOI:10.1246/cl.2001.1110

1110
Chemistry Letters 2001
An Efficient Enantioselective Preparation of (S,S)-1,2-Bis(1-hydroxyalkyl)benzene
Masatoshi Asami,* Masaaki Wada, and Sanae Furuya
Department of Advanced Materials Chemistry, Graduate School of Engineering, Yokohama National University,
79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501
(Received July 24, 2001; CL-010695)
(S,S)-1,2-Bis(1-hydroxyalkyl)benzenes were obtained in
materials were recovered in both reactions, we focused our
efforts on the reaction of 2-(1-alkoxyalkyl)benzaldehyde
(Scheme 1).
>99% ee’s with high diastereoselectivity by the enantioselective
addition of dialkylzinc to (S)-2-[1-(4-methoxybenzyloxy)alkyl]-
benzaldehyde (86% ee) in the presence of a catalytic amount of
(S)-2-(4-methylpiperazin-1-ylmethyl)indoline.
(S)-2-[1-(4-methoxybenzyloxy)propyl]benzaldehyde, (S)-2
was employed as 2-(1-alkoxyalkyl)benzaldehyde since 4-
methoxybenzyl group was removed selectively in the presence
of benzylic hydroxyl group under mild reaction conditions. In
the first place 2-bromobenzaldehyde was converted to (S)-1-(2-
C2-Symmetric chiral 1,2-, 1,3-, and 1,4-diols are useful
reagents in asymmetric synthesis1 as chiral auxiliaries, chiral
ligands, and starting materials for various chiral compounds
having other functionalities.2 Asymmetric dihydroxylation of
olefins3 and asymmetric reduction of diketones are successfully
employed for the preparation of this class of compounds.4
Enantioselective alkylation of dialdehyde was also examined
using B-allyldiisopinocamphenylborane5 or dialkylzinc in the
presence of a chiral catalyst.6,7 However, (R,R)-1,2-bis(1-
hydroxypropyl)benzene of 92% ee was obtained only as a
minor product (dl/meso = 9/91) in the catalytic diethylation of
phthalaldehyde.7b With regard to the asymmetric reduction of
1,2-diacylbenzenes to produce chiral 1,2-bis(1-hydroxyalkyl)-
benzene, catalytic oxazaborolidine-BH3 reduction gave chiral
1,2-bis(1-hydroxyethyl)benzene in 90% ee (48%)8 while B-
chlorodiisopinocamphenylborane gave unsuccessful result.9
These results prompted us to develop an efficient method to
prepare chiral 1,2-bis(1-hydroxyalkyl)benzene in high ee and
examine its use in asymmetric synthesis. In this communica-
tion we wish to report an efficient method for the preparation of
(S,S)-1,2-bis(1-hydroxyalkyl)benzene starting from 2-bromo-
benzaldehyde by dual enantioselective addition of dialkylzinc
to aldehyde using (S)-2-(4-methylpiperazin-1-yl)methylindoline
(1)10 as catalyst.
20
bromophenyl)propanol, (S)-311 (86% ee, [α]D –40.4° (c 1.32,
CHCl3)) in 92% yield by catalytic enantioselective addition of
diethylzinc using 15 mol% 1. After treatment of (S)-3 with 4-
methoxybenzyl chloride (MPMCl), ((S)-4,12 90%, [α]D20 –42.1°
(c 1.02, CHCl3)), (S)-2-(1-(4-methoxybenzyloxy)propyl)-
20
benzaldehyde, (S)-212 ([α]D –92.4° (c 1.00, CHCl3)) was
obtained in 92% yield by lithiation of (S)-4 with butyllithium
followed by the reaction with DMF (Scheme 2).
First we examined reactions of excess diethylzinc with
phthalaldehyde or 2-(1-hydroxypropyl)benzaldehyde (1-
hydroxy-3-ethyl-2-oxaindane) in cyclohexane at room tempera-
ture using 40 mol% or 10 mol% 1, respectively. As the starting
Enantioselective ethylation of (S)-2 was then examined
using 1.8 equiv diethylzinc in the presence of 20 mol% 1 in
cyclohexane. A mixture of stereoisomers of 1-[2-{1-(4-
methoxybenzyloxy)propyl}]phenylpropanol (5)12 was obtained
in 84% yield along with 1-[2-{1-(4-methoxybenzyloxy)-
propyl}]benzyl alcohol, 612 (6% yield). Removal of the pro-
tecting group of 5 with cerium ammonium nitrite (CAN) in
20
CH3CN/H2O (9/1)13 afforded (S,S)-714 (84%, >99% ee, [α]D
–55.4° (c 0.87, CHCl3)) and meso-77b (8%) (dl/meso = 91/9)
(Scheme 3).
We assume that the second addition reaction is irrelevant to
the other chiral center formed in the first addition reaction and
the enantioselectivity of the second addition reaction is high for
both (S)- and (R)-2. Thus (S)-2, the major enantiomer in the
first addition reaction, afforded exclusively (S,S)-5 with a small
amount of meso-type 5. On the other hand, most of (R)-2, the
minor enantiomer in the first addition reaction, was converted
to meso-type 5 and little (R,R)-5 was formed. Consequently,
(S,S)-7 was obtained in high (>99%) ee with a small amount of
easy separable meso-7 after removal of protecting group.
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
1111
References and Notes
1
For a review on C2 symmetry and asymmetric induction,
see J. K. Whitesell, Chem. Rev., 89, 1581 (1989).
For example, R. A. Johnson, K. B. Sharpless, in “Catalytic
Asymmetric Synthesis,” ed. by I. Ojima, VCH Publishers,
New York (1993), p 103; D. Seebach and B. Weber,
Tetrahedron, 50, 7473 (1994); J. M. Chong, I. S. Clarke, I.
Koch, P. C. Olbach, and N. J. Taylor, Tetrahedron:
Asymmetry, 6, 409 (1995); K. Yamaguchi, T. Sugimura, F.
Nishida, and A. Tai, Tetrahedron Lett., 39, 4521 (1998); H.
Ishitani, M. Ueno, and S. Kobayashi, J. Am. Chem. Soc.,
122, 8180 (2000).
2
3
4
H. C. Kolb, M. S. VanNieuwenhze, and K. B. Sharpless,
Chem. Rev., 94, 2483 (1994).
M. Kitamura, T. Ohkuma, S. Inoue, N. Sayo, H.
Kumobayashi, S. Akutagawa, T. Ohta, H. Takaya, and R.
Noyori, J. Am. Chem. Soc., 110, 629 (1988); G. J.
Quallich, K. N. Keavey, and T. M. Woodall, Tetrahedron
Lett., 36, 4729 (1995).
Next enantio- and diastereoselective synthesis of (S,S)-1,2-
bis(1-hydroxyethyl)benzene, (S,S)-8, was examined by a similar
reaction sequence. (S)-2-[1-(4-Methoxybenzyloxy)ethyl]-ben-
20
zaldehyde, (S)-1112,15 (86% ee, [α]D –83.1° (c 1.02, CHCl3))
5
6
7
P. V. Ramachandran, G.-M. Chen, and H. C. Brown,
Tetrahedron Lett., 38, 2417 (1997).
K. Soai, H. Hori, and M. Kawahara, J. Chem. Soc., Chem.
Commun., 1992, 106.
a) M. Watanabe, N. Hashimoto, S. Araki, and Y. Butsugan,
J. Org. Chem., 57, 742 (1992). b) K. Soai, Y. Inoue, T.
Takahashi, and T. Shibata, Tetrahedron, 52, 13355 (1996).
X. Zhang, U. S. Patent 5767276 (1998); Chem. Abstr., 129,
81855q (1998).
was obtained from 2-bromobenzaldehyde in three steps in 82%
yield. The second addition reaction afforded a mixture of
stereoisomers
of
1-[2-{1-(4-methoxybenzyloxy)-
20
ethyl}]phenylethanol, 1212 in 85% yield, and S,S-88,16 ([α]D
–72.4° (c 1.00, CHCl3)) was obtained in 84% yield in high
(>99%) ee along with meso-817 (7% yield) (dl/meso = 92/8)
after deprotection with CAN (Scheme 4).
8
9
P. V. Ramachandran, G.-M. Chen, Z.-H. Lu, and H. C.
Brown, Tetrahedron Lett., 37, 3795 (1996).
10 M. Asami, H. Watanabe, K. Honda, and S. Inoue,
Tetrahedron: Asymmetry, 9, 4165 (1998).
11 The ee value was determined by HPLC using Daicel
Chiralcel OB and the absolute configuration was assigned
to be S as (S,S)-7 was obtained afterwards.
12 Satisfactory spectral data (1H NMR, 13C NMR, IR) were
obtained for these compounds.
13 R. Johansson and B. Samuelson, J. Chem. Soc., Perkin
Trans. 1, 1984, 2371.
14 The ee value was estimated to be >99% as only one enan-
tiomer was detected by HPLC using Daicel Chiralcel OD-
H. The absolute configuration was established by compari-
son of the specific rotation with reported value.7b
20
15 The ee value of (S)-9 ([α]D –47.8° (c 1.00, CHCl3)) was
determined to be 86% by HPLC using Daicel Chiralcel OB
and the absolute configuration of (S)-9 was established by
comparison of the specific rotation with reported value; S.
Sato, H. Watanabe, and M. Asami, Tetrahedron:
Asymmetry, 11, 4329 (2000).
16 The ee value was estimated to be >99% as only one enan-
tiomer was detected by HPLC using Daicel Chiralcel OD-
H. The absolute configuration was assigned to be S,S as the
chiral center created in the first reaction was S.
17 I. Fleming, I. T. Morgan, and A. K. Sarkar, J. Chem. Soc.,
Perkin Trans. 1, 1998, 2749.
It should be noted that an efficient enantio- and diastereo-
selective synthesis of chiral 1,4-diols, (S,S)-1,2-bis(1-hydroxy-
propyl)benzene, (S,S)-7, and (S,S)-8, were achieved using catalyt-
ic dual enantioselective addition of dialkylzinc to aldehydes,
starting from 2-bromobenzaldehyde. As the usefulness of (S,S)-7
was realized in an asymmetric photochromic cyclization,18 fur-
ther applications of the chiral 1,4-diols in asymmetric synthesis is
now in progress.
18 Y. Yokoyama, T. Okuyama, Y. Yokoyama, and M. Asami,
Chem. Lett., 2001, 1112.