LETTER
1927
Distannoxane-Catalyzed Selective Acetylation of 3-Chloropropane-1,2-diol:
A Convenient Synthesis of Enantiopure Epichlorohydrin
Akihiro Orita, Toshihide Ito, Yutaka Yasui, Junzo Otera*
Department of Applied Chemistry, Okayama University of Science, Ridai-cho, Okayama 700-0005, Japan
Received 31 August 1999
We earlier reported efficient acylation of alcohols with
Abstract: A distannoxane catalyst effects exclusive acetylation of
alkenyl acetates or acetic anhydride (Ac2O) under cataly-
the primary alcohol of 3-chloropropane-1,2-diol. This reaction pro-
sis of distannoxane, but attempts for the monoacetylation
vides a convenient access to enantiopure epichlorohydrin.
of octane-1,2-diol failed resulting in a mixture of primary
Key words: epichlorohydrin, acetylation, 1,2-diol, distannoxane
and secondary monoacetates together with the diacetate.10
To our surprise, however, when (R)-1 was stirred in Ac2O
in the presence of 1,3-dichlorotetrabutyldistannoxane (2)
(10 mol%) at 30 °C for 20 h, the primary monoacetate (R)-
3 was exclusively formed (79%) along with diacetate 5
(20% yield) (eq 1). The regioisomer, 2-acetoxy-3-
The synthesis of enantiopure epichlorohydrin in a practi-
cal way has received increasing attention due to its syn-
thetic utilities for pharmaceutical and ferro-electric
materials.1 Enzymatic hydrolysis of racemic 1-acetoxy-
choloro-1-propanol (4), was not detected on the basis
2,3-dichloropropane gave the S-enantiomer (90% ee) of
this substrate (20% yield) that was converted to epichlo-
rohydrin through alkaline hydrolysis.2 Racemic 2,3-
Ac2O/2
Cl
OAc
+
Cl
OAc
Cl
OH
dichloropropanol was resolved by the aid of an assimilat-
ing bacterium to give quantitatively both enantiomers in
100% ee.3 The R-isomer thus obtained was converted to
(S)-epichlorohydrin (99.5% ee). A multi-step procedure
with recourse to enzymatic hydrolysis of 2-acyloxy-3-
chloropropyl tosylate that had been obtained by tosylation
of racemic epichlorohydrin followed by acylation afford-
ed both enantiomers with >99% ee.4 Recently, a highly
practical method was disclosed by which an R-enantiomer
(>99% ee) was obtained directly from racemic epichloro-
hydrin upon hydrolytic kinetic resolution with (S,S)-
(salen)Co (II) complex.5,6
OH
30°C, 20 h
OAc
OH
(R)-5
(R)-3
(R)-1
79%, 99.7% ee
20%
99.7% ee
Equation 1
1
of H NMR. No decrease of the enantiopurity occurred
during the reaction. It may be noted, however, that such
perfect regioselectivity is not innate in the reaction be-
tween 1 and Ac2O since the ratio of 3 and 4 was 96:4 (29%
combined yield together with 2% yield of 5) after 30 min
and 98:2 (33% combined yield together with 3% yield of
5) after 1 h, respectively.11 After 3 h, 4 disappeared com-
pletely. Consequently, the exclusive formation of 3 is rea-
sonably accounted for in terms of much faster
consumption of primary alcohol 4 to give 5 in addition to
the excellent selectivity in the monoacetylation step. Use
of vinyl or isopropenyl acetate in place of Ac2O under the
similar conditions failed to give rise to such perfect out-
come (Scheme 2). The 3/4 ratio attained with vinyl acetate
was excellent (96:4) but not perfect. In this case, the ratio
was nearly constant from the beginning of the reaction
and thus no improvement of the ratio was brought about
by conversion of the monoacetates to the diacetate. The
employment of isopropenyl acetate led to a lower ratio
(85:15). Furthermore, mention should be made that the
high preference for the monoacetates could not be
Despite these achievements another promising route start-
ing from 3-chloropropane-1,2-diol (1) (Scheme 1) re-
mains to be explored since the successful cultivation of
this compound in more concentrated solution than 2,3-
dichloropropanol enables more facile and cheaper access
to enantiopure 1 in industrial scale.7 The key feature of
this process rests on the selective monoacetylation of the
diol moiety. The exclusive acetylation of the primary al-
cohol is crucial because the contamination of the insepa-
rable secondary acetate decreases the enantiopurity of the
epichlorohydrin to be produced. In general, the
monoacetylation of 1,2-diol in a exclusive manner is very
difficult.8 We report herein that a distannoxane catalyst9
works well to this end and thus the practical process for
enantiopure epichlorohydrin is feasible.
12
achieved with other Lewis acid catalysts like Sc(OTf)3
and TMSOTf:13 the use of 1 equiv of Ac2O with 1 mol%
catalyst afforded the monoacetates and diacetate in ca.
20:80 ratio while only the diacetate was formed with 10
equiv of Ac2O. It is evident therefore that the distannox-
ane catalyst is unique in that the rate of the monoacetate
formation from the diol is much faster than that of the di-
acetate formation.
Cl
OH
Cl
OAc
Cl
OAc
OH
OH
Br
Cl
OH
Cl
O
Br
Scheme 1
Synlett 1999, No. 12, 1927–1929 ISSN 0936-5214 © Thieme Stuttgart · New York