Novel ring-opening of epoxides and oxetanes with POCl3 or PCl3 in the presence of DMAP

Article abstract of DOI:10.1016/S0040-4039(01)02088-3

Efficient synthesis of chlorohydrins by cleavage of oxiranes and oxetanes using POCl₃ or PCl₃ in the presence of DMAP (4-N,N-dimethylaminopyridine) has been studied.

Full text of DOI:10.1016/S0040-4039(01)02088-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 15–17
Novel ring-opening of epoxides and oxetanes with POCl or
3
PCl in the presence of DMAP
3
a,
a,
a
b
Fernando Sartillo-Piscil, * Leticia Quintero, * Clarisa Villegas, Ericka Santacruz-Ju a´ rez and
b,
Cecilia Anaya de Parrodi *
a
Centro de Investigaci o´ n de la Facultad de Ciencias Qu ´ı micas, Universidad Aut o´ noma de Puebla, 72570 Puebla, Puebla, Mexico
Departamento de Qu ´ı mica y Biolog ´ı a, Universidad de las Am e´ ricas-Puebla, 72820 Santa Catarina M a´ rtir, Puebla, Mexico
b
Received 19 September 2001; accepted 12 October 2001
Abstract—Efficient synthesis of chlorohydrins by cleavage of oxiranes and oxetanes using POCl3 or PCl3 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
entry 12) to obtain the 2-choro-cyclohexanol, otherwise
13
the 1,2-dichlorocyclohexane was recovered.
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. Meth-
ods based upon hydrogen chloride are not considered
appropriate because of the formation of some
unwanted byproducts and low regioselectivities.
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
1
2
14
regioselectivities were obtained using POCl3.
Ring-opening of asymmetrically substituted oxiranes
Besides, we observed that (R)-(+)-styrene oxide reacts
enantioselectively with inversion of configuration on
the stereogenic center yielding (S)-(+)-2-chloro-2-
3
had been reported with chlorosilanes, haloborane
4
5
6
7
reagents, Br /PPh , Me SiBr, Py·HCl,9 Lewis acid
2
8
3
3
+
−
metal halides, complex halide metal salts, n-Bu N Br
phenylethanol, 98% e.e. by HPLC analysis, [h] =
4
D
1
0
/
Mg(NO ) , and elemental I and Br in the presence
+116.1 (c=1, CHCl ), meanwhile Kotsuki et al. report
3
2
2
2
3
1
1
of catalysts. 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
[h] =+30.7 (c=1, CHCl3), 18% e.e. by HPLC
D
15
analysis.
Based on the results we observed a rigorously S 2 type
N
mechanism. The reaction occurred by nucleophilic
attack of the chloride ion which is formed by the
reaction between DMAP and phosphorus atom of
−
−
− 1
halides: I >Br >Cl .
POCl3 or PCl , leading to a complex, which was
3
16
We have examined this reaction and report the opening
of symmetric and asymmetric epoxides and oxetanes
observed by NMR.
(
see Table 1, entries 1–14), with POCl or PCl in the
On behalf of our interest in halohydrins, this work is
still in progress in our laboratory.
3
3
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
Acknowledgements
1
0–12) was treated under milder conditions (−78°C,
We thank CONACYT for financial support (Projects
35102-E and 32202-E).
*
Corresponding authors. E-mail: lquinter@siu.buap.mx
0
040-4039/02/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02088-3

1
6
F. Sartillo-Piscil et al. / Tetrahedron Letters 43 (2002) 15–17
Table 1. Ring-opening reaction with different reagents and conditions
Entry
Substrate
MeCO2CH2
Major regioisomer
Reagents and conditionsa
Regioselectivity (%)b
Yield (%)c
1
2
3
4
1
1
1
1
Ph MeCO2CH2CHCHPhCl
OH
POCl3 (3:3)/rt
POCl3 (1:1)/rt
PCl3 (3:3)/rt
PCl3 (1:1)/rt
100
87
86
73
79
75
73
O
66
d
5
2
Cl
POCl3 (3:3)/rt
100
80
H
HOCH2
H
Ph
Ph
O
(
R)-(+)
(
S)-(+)
d
6
7
2
3
POCl3 (1:1)/rt
POCl3 (3:3)/rt
100
84
85
80
PhCH2
2 2
PhCH CHCH Cl
OH
O
8
9
3
3
POCl3 (1:1)/rt
PCl3 (1:1)/rt
84
83
70
80
e
e
1
1
0
1
4
4
POCl3 (3:3)/rt
POCl3 (3:3)/−40°C
–
–
OH
O
Cl
1
2
3
4
5
PCl3 (1:1)/−78°C
POCl3 (3:3)/rt
–
–
85
80
1
CH3
O
HOCH2CCH2Cl
CH3
12
1
4
6
O
O
Cl
O
POCl3 (3:3)/rt
100
77
O
OH
O
O
O
a
b
c
The epoxide or oxetane (1 equiv.) reacts with DMAP (1–3 equiv.) and PCl3 or POCl3 (1–3 equiv.) at the indicated temperature in each entry.
Regioselectivity was measured by GC and NMR.
Isolated yield after column chromatography on silica gel.
d
e
The stereochemical outcome was determined by optical rotation and HPLC (Chiralcel OD).
1
,2-Dichlorocyclohexane was the main product (80% yield).
4
. (a) Guindon, Y.; Therien, M.; Girard, Y.; Yoakim, C. J.
Org. Chem. 1987, 52, 1680; (b) Joshi, N. N.; Srebnik, M.;
Brown, H. C. J. Am. Chem. Soc. 1988, 110, 6246; (c) Bell,
T. W.; Ciaccio, J. A. Tetrahedron Lett. 1986, 27, 827; (d)
Mandal, A. K.; Soni, N. R.; Ratnam, K. R. Synthesis
References
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985, 274.
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F. Sartillo-Piscil et al. / Tetrahedron Letters 43 (2002) 15–17
17
Org. Chem. 1992, 57, 5140; (b) Shimizu, M.; Yoshida, A.;
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13. General procedure: In a two-necked flask provided with a
thermometer and a magnetic stirrer, under argon, the
epoxide or the oxetane (1–6, 1 mmol) and DMAP (1–3
3
(
f) Azzena, F.; Calvani, F.; Crotti, P.; Gardelli, C.;
Macchia, F.; Pineschi, M. Tetrahedron 1995, 51, 10601–
0626.
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990, 55, 3429; (b) Dawe, R. D.; Molinski, T. F.; Turner,
mmol) were dissolved in dry CH Cl2 (30 mL). To the
2
mixture was added dropwise POCl or PCl (1–3 mmol) in
3
3
1
dry CH Cl (5 mL). The reaction mixture was stirred until
2
2
9
no more epoxide or oxetane (1–6) was detected by TLC
ca. 30–45 min). Finally, the reaction mixture was neutral-
ized and extracted with CH Cl (3×25 mL). The combined
1
(
J. V. Tetrahedron Lett. 1984, 25, 2061; (c) Mincione, E.;
Ortaggi, G.; Sirna, A. J. Org. Chem. 1979, 44, 1569–1570;
2
2
organic extracts were dried over Na SO , filtered and
2
4
(
d) Ciaccio, J. A.; Heller, E.; Talbot, A. Synlett 1991,
48–250.
0. Suh, Y. G.; Koo, B. A.; Ko, J. A.; Cho, Y. S. Chem. Lett.
993, 1907.
concentrated in vacuo. The crude products were purified
by flash chromatography.
2
1
1
1
4. The regiochemistry on the opening of trans-cinnamyl-
acetate, 1 (entries 1–4) has been unequivocally established
by the exclusive formation of both regioisomers.
5. Kotsuki, H.; Shimanouchi, T.; Ohshima, R.; Fujiwara, S.
Tetrahedron 1998, 54, 2709–2722.
1
1. (a) Konaklieva, M. I.; Dahi, M. L.; Turos, E. Tetrahedron
Lett. 1992, 33, 7093; (b) Sharghi, H.; Massah, A. R.;
Eshghi, H.; Niknam, K. J. Org. Chem. 1998, 63, 1455–
1
1
1
5
461; (c) Sharghi, H.; Naeimi, H. J. Chem. Res. (S) 1999,
, 310–311.
1
6. H NMR spectra of the complex show signals at 8.21 and
31
8
.70, compared to 6.47 and 7.79 for free DMAP, and
NMR spectra shows a signal at 10.01 ppm, compared to
5.00 for free POCl
P
1
2. 3,5-Anhydro-1,2-O-isopropylidene-a-
was synthesized from diacetone-a- -glucose, [h] =+11.24
c=1, CHCl ), and compare with literature ([h] =+12.0
D-xylofuranose, 6,
D
D
(
.
3
3
D
.