TETRAHEDRON
LETTERS
Tetrahedron Letters 43 (2002) 15–17 Pergamon
Novel ring-opening of epoxides and oxetanes with POCl
3
or
PCl
3
in the presence of DMAP
Fernando Sartillo-Piscil,
a,
* Leticia Quintero,
a,
* Clarisa Villegas,
a
Ericka Santacruz-Jua ´rez
b
and
Cecilia Anaya de Parrodi
b,
*
a
Centro de Investigacio ´n de la Facultad de Ciencias Quı ´micas, Universidad Auto ´noma de Puebla, 72570 Puebla, Puebla, Mexico
b
Departamento de Quı ´mica y Biologı ´a, Universidad de las Ame ´ricas -Puebla, 72820 Santa Catarina Ma ´rtir, Puebla, Mexico
Received 19 September 2001; accepted 12 October 2001
Abstract—Efficient synthesis of chlorohydrins by cleavage of oxiranes and oxetanes using POCl
3
or PCl
3
in the presence of
DMAP (4-N,N-dimethylaminopyridine) has been studied. © 2001 Elsevier Science Ltd. All rights reserved.
There is a continued interest in the regioselective ring-
opening of oxiranes and oxetanes to the corresponding
1,2 and 1,3 halohydrins. Although a variety of new and
mild procedures to make this transformation have been
reported, most of them have some limitations.
1
Meth-
ods based upon hydrogen chloride are not considered
appropriate because of the formation of some
unwanted byproducts and low regioselectivities.
2
Ring-opening of asymmetrically substituted oxiranes
had been reported with chlorosilanes,
3
haloborane
reagents,
4
Br
2
/PPh
3
,
5
Me
3
SiBr,
6
Py·HCl,
7
Lewis acid
metal halides,
8
complex halide metal salts,
9
n -Bu
4
N
+
Br
-
/Mg(NO
3
)
2
,
10
and elemental I
2
and Br
2
in the presence
of catalysts.
11
However, some of these methods are not
always fully satisfactory and suffer from disadvantages
such as acidity, handling and in situ preparation of
reagent or relative long reaction times. Besides, not all
the above-mentioned methodologies are suitable to give
chlorohydrins, due to the reactivity order of the three
halides: I
-
>Br
-
>Cl
-
.
1
We have examined this reaction and report the opening
of symmetric and asymmetric epoxides and oxetanes
(see Table 1, entries 1–14), with POCl
3
or PCl
3
in the
presence of DMAP in dichloromethane in high yields
(70–85%) under mild conditions, at rt over 30–45 min
even when sensitive functional groups are present in the
molecules. Nevertheless, cyclohexene oxide, 4 (entries
10–12) was treated under milder conditions (-78°C,
entry 12) to obtain the 2-choro-cyclohexanol, otherwise
the 1,2-dichlorocyclohexane was recovered.
13
The attack of the chloride ion in the asymmetric rings
proceeds on the carbon atom with the most favorable
electronic effects (substrates 1 and 2) or on the less
hindered carbon atom (substrates 3 and 6). The higher
regioselectivities were obtained using POCl
3
.
14
Besides, we observed that (R )-(+)-styrene oxide reacts
enantioselectively with inversion of configuration on
the stereogenic center yielding (S )-(+)-2-chloro-2-
phenylethanol, 98% e.e. by HPLC analysis, [ ]
D
=
+116.1 (c=1, CHCl
3
), meanwhile Kotsuki et al. report
[ ]
D
=+30.7 (c=1, CHCl
3
), 18% e.e. by HPLC
analysis.
15
Based on the results we observed a rigorously S
N
2 type
mechanism. The reaction occurred by nucleophilic
attack of the chloride ion which is formed by the
reaction between DMAP and phosphorus atom of
POCl
3
or PCl
3
, leading to a complex, which was
observed by NMR.
16
On behalf of our interest in halohydrins, this work is
still in progress in our laboratory.
Acknowledgements
We thank CONACYT for financial support (Projects
35102-E and 32202-E). * Corresponding authors. E-mail: lquinter@siu.buap.mx
0040-4039/02/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII:S0040-4039(01)02088-3