An unexpected 1,2-hydride shift in phosphoric acid-promoted cyclodimerization of styrene oxides under solvent-free conditions. A synthetic route towards 2,4-disubstituted 1,3-dioxolanes

Article abstract of DOI:10.1016/j.tetlet.2009.08.044

A 1,2-hydride shift in the phosphoric acid-promoted cyclodimerization of styrene oxide and its chloro derivatives under solvent-free conditions leading to 2,4-disubstituted 1,3-dioxolanes is described. Methoxy substituents on the aromatic ring of the styr

Full text of DOI:10.1016/j.tetlet.2009.08.044

Tetrahedron Letters 50 (2009) 5927–5929
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An unexpected 1,2-hydride shift in phosphoric acid-promoted
cyclodimerization of styrene oxides under solvent-free conditions.
A synthetic route towards 2,4-disubstituted 1,3-dioxolanes
*
Ofentse Mazimba, Runner R. Majinda, Ishmael B. Masesane
Department of Chemistry, University of Botswana, Private Bag UB 00704, Gaborone, Botswana
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 June 2009
Revised 17 July 2009
Accepted 14 August 2009
Available online 20 August 2009
A 1,2-hydride shift in the phosphoric acid-promoted cyclodimerization of styrene oxide and its chloro
derivatives under solvent-free conditions leading to 2,4-disubstituted 1,3-dioxolanes is described.
Methoxy substituents on the aromatic ring of the styrene oxide prevent the 1,2-hydride shift reaction
leading to substituted 1,4-dioxanes. A possible mechanism for the formation of the 1,3-dioxolanes is
proposed.
Ó 2009 Elsevier Ltd. All rights reserved.
The chemistry of epoxides has attracted significant attention
mainly as a result of their highly regio- and stereoselective ring-
opening reactions and their potential as building blocks for the
synthesis of a wide range of biologically active oxygen-containing
compounds. Their synthetic utility is based on the fact that they
undergo ring-opening with a broad range of nucleophiles.1–9
To the best of our knowledge, the preparation of 1,3-dioxolanes
utilizing acid-promoted cyclodimerization of epoxides has not been
reported. In connection with a project exploiting the use of styrene
oxides in synthesis, we report herein our preliminary results on the
serendipitous synthesis of 2,4-disubstituted 1,3-dioxolanes via cyc-
lodimerization of styrene oxides under solvent-free conditions. This
cyclodimerization reaction was discovered whilst we were investi-
gating the use of phenols in acid-mediated epoxide ring-opening
reactions. 1,3-Dioxolanes are often prepared by reactions of oxiranes
with carbonyl compounds in the presence of Brønsted or Lewis acids
including BF3, CuSO4, Bi(III), Sn(IV), Ti(IV), Ir, Ru(III) and Re cata-
lysts.10–12 The alternative route described herein involves a 1,2-hy-
dride shift during the cyclodimerization of styrene oxides.
which there was correlation observed between H-4 and the meth-
ylene protons of the benzyl substituent.
We wondered whether various groups situated at different
positions on the phenyl ring of a styrene oxide would have any ef-
fect on the cyclodimerization. To this end, ortho-, meta- and para-
chlorostyrene oxides 4, 6 and 8 were prepared using the method
described above and then subjected to the solvent-free cyclodi-
merization conditions to give a mixture of trans/cis isomers of
the corresponding dimers 5, 7 and 9,13 respectively, in high yields
and stereoselectivity for the trans isomer (Scheme 2). Interestingly,
and perhaps somewhat surprisingly, p-chlorostyrene oxide gave
exclusively the trans-isomer while its ortho- and meta-analogues
gave a 75:25 mixture of trans and cis isomers. The reason for this
discrepancy is not clear. On the basis of these findings, it appears
that the position of the chloro group on the aromatic ring does
not have any effect on the cyclodimerization of styrene oxides to
1,3-dioxalanes. Chlorine is an electron-withdrawing substituent
and hence it is assumed that other electron-withdrawing groups
would favour the formation of 1,3-dioxolanes.
Styrene oxide 2 was readily prepared from styrene 1 in 88%
yield using mCPBA (Scheme 1) and initial experiments were per-
formed using 2 as a model substrate. Thus, stirring a solution of
epoxide 2 in H3PO4 at room temperature gave a 75:25 mixture of
trans-3 and cis-3 in good yield. Various organic and inorganic acids
were tested, but only perchloric acid was found to be equally effec-
tive in promoting the cyclodimerization reaction. The major isomer
trans-3 was purified by column chromatography and characterized
by NMR spectroscopy.13 The relative stereochemistry of trans-3
was assigned using 2D NMR experiments, particularly NOESY in
A possible mechanism for this cyclodimerization reaction
would involve protonation and ring-opening of epoxide 2 to give
the benzyl cation 10. Cation 10 is attacked by another molecule
of epoxide 2 to give the dimeric benzyl cation 11 which can cyclize
to form 1,4-dioxane 12. In order to form the 1,3-dioxalane, a 1,2-
hydride shift occurs to give the cation 13 which is stabilized by res-
onance structure 13a. Cyclization of 13 then occurs to give 2-ben-
zyl-4-phenyl-2,3-dioxolane 14 (Scheme 3). The observation that
the 1,2-hydride shift in 11 to give 13 was faster than the cycliza-
tion reaction to give dioxane 12 was a striking aspect of this work.
It can be assumed that stabilization of the carbocation by the oxy-
gen in resonance structures 13 is more pronounced than that by
the phenyl group in structure 11. The electron-withdrawing chlo-
* Corresponding author. Tel.: +267 3552495; fax: +267 3552836.
E-mail address: masesane@mopipi.ub.bw (I.B. Masesane).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.08.044

5928
O. Mazimba et al. / Tetrahedron Letters 50 (2009) 5927–5929
O
O
O
O
O
(ii)
(i)
+
1
2
trans-3
cis-3
Scheme 1. Reagents and conditions: (i) mCPBA, CH2Cl2, NaHCO3, 25 °C, 88%; (ii) H3PO4, 25 °C, 61% (trans-3:cis-3, 75:25).
Cl
Cl
O
O
O
O
O
(i)
Cl
+
Cl
Cl
o-Chloro; 4
m-Chloro;6
p-Chloro; 8
trans-5
trans-7
trans-9
cis-5
cis-7
cis-9
Scheme 2. Reagents and conditions: (i) H3PO4, 25 °C, 72% [5 (trans-5:cis-5 75:25)], 62% [ 7 (trans-7:cis-7 75:25)], 65% [9 (trans-9:cis-9 100:0)].
H
Ph
Ph
OH
O
O
O
O
H
OH
Ph
O
Ph
Ph
Ph
Ph
2
10
11
12
1,2-hydride
shift
Ph
Ph
OH
O
Ph
O
cyclisation
O
O
Ph
OH
Ph
Ph
14
13
13a
Scheme 3. A possible mechanism for the cyclodimerization of styrene oxide to 1,3-dioxolanes.
rine atom on the phenyl ring further destabilizes the benzyl carbo-
cation of 11 and therefore accelerates the 1,2-hydride shift.
Next, we decided to investigate the effects of methoxy groups
(electron-donating) on the aromatic ring on the cyclodimerization.
To this end, methoxystyrenes 15 and 17 were subjected to the
epoxidation conditions and interestingly, and perhaps somewhat
surprisingly, 1,4-dioxanes 16 and 1813 were isolated in good yields
instead of the expected epoxides (Scheme 4). Concellon et al. have
reported the cyclodimerization of epoxides to 1,4-dioxanes pro-
moted by Lewis acids.14 It is therefore logical to suggest that this
cyclodimerization reaction is promoted by the m-chlorobenzoic
acid generated during the epoxidation reaction. We suggest that
the methoxy group further stabilizes benzyl cation 11 by resonance
thereby preventing the occurrence of 1,2-hydride shift. It is reason-
able to expect that other electron-donating groups on the aromatic
ring of styrene oxide would also prevent the 1,2-hydride shift.
In summary we have reported a 1,2-hydride shift in the cyclod-
imerization of styrene oxides which proceeds under fairly mild
conditions to give 1,3-dioxolanes. We have also shown that chloro
groups on the phenyl ring of styrene favour the 1,2-hydride shift
leading to substituted 1,3-dioxolanes while methoxy groups pre-
vent the hydride shift resulting in the formation of substituted
1,4-dioxanes instead. Further studies on the effects of other sub-
stituents on the aromatic ring of styrene oxide on the cyclodimer-
ization reaction are currently under investigation in our laboratory.
Acknowledgements
This work was supported financially by the Royal Society of
Chemistry. O.M. is grateful to the Chemistry Department, Univer-
sity of Botswana for a fellowship. We thank Miss G. Ramokongwa
for assistance with NMR experiments and Dr. K. Sichilongo for mass
spectra. We also thank Dr. P. G. Steel (University of Durham, UK) for
donating columns for flash chromatography to our laboratory.
MeO
O
(i)
MeO
O
OMe
References and notes
p-methoxy:
15
16
18
3,4-dimethoxy: 17
1. Chola, J.; Masesane, I. B. Tetrahedron Lett. 2008, 49, 5680.
2. Bwire, R. N.; Majinda, R. R.; Masesane, I. B. Pure Appl. Chem. 2009, 81, 105.
3. Smith, J. C. Synthesis 1984, 629.
Scheme 4. Reagents and conditions: (i) mCPBA, CH2Cl2, NaHCO3, 25 °C, 85% (16),
96% (18).

O. Mazimba et al. / Tetrahedron Letters 50 (2009) 5927–5929
5929
4. Olah, G.; Fung, A. P.; Meidar, D. Synthesis 1981, 280.
5. Iranpoor, N.; Salehi, P. Tetrahedron 1995, 51, 909.
6. Concellon, J. M.; del Solar, V.; Suarex, J. R.; Blanco, E. G. Tetrahedron 2007, 63,
2805.
7. Concellon, J. M.; Bernad, P. L.; del Solar, V.; Suarez, J. R.; Garcia-Granda, S.; Diaz,
M. R. J. Org. Chem. 2006, 71, 6420.
8. Concellon, J. M.; Suarez, J. R.; del Solar, V.; Llavona, R. J. Org. Chem. 2005, 70,
10348.
9. Concellon, J. M.; Suarez, J. R.; del Solar, V. J. Org. Chem. 2005, 70, 7447.
10. Concellon, J. M.; Suarez, J. R.; Garcia-Granda, S.; Diaz, M. R. Org. Lett. 2005, 7,
247.
11. Otera, J.; Yashinaga, Y.; Hirakama, H. Tetrahedron Lett. 1985, 26, 3219.
12. Chini, M.; Crotti, P.; Favero, L.; Macchina, F.; Pineschi, M. Tetrahedron Lett. 1994,
35, 433.
13. Satisfactory spectroscopic and analytical data were obtained for all the new
compounds. trans-3: Colourless gum; mmax (KBr): 3028, 2923, 2875, 1596,
1446, 1024, 754 cmꢀ1; dH (300 MHz, CDCl3): 3.24 (2H, d, J = 5.7, PhCH2), 3.75
(1H, dd, J = 7.8 Hz, 6.3 Hz, H-5), 4.22 (1H, dd, J = 7.8 Hz, 1.9 Hz, H-5), 5.06 (1H,
dd, J = 6.3 Hz, 1.9 Hz, H-4), 5.38 (1H, t, J = 5.7 Hz, H-2), 7.39–7.44 (10H, m,
aromatic protons); dC (75 MHz, CDCl3): 40.8 (PhCH2), 72.0 (C-5), 78.5 (C-4),
105.4 (C-2), 126.4 (C-200, C-600), 126.7 (C-400), 128.1 (C-10), 128.3 (C-300, C-500),
128.5 (C-20, C-60), 130.0 (C-30, C-50), 136.0 (C-10), 139.4 (C-100). HRMS (EI) found
M+, 240.1692. C16H16O2 requires 240.1601. cis-3: Yellow gum; mmax (KBr):
3032, 2918, 2885, 1581, 1438, 1031, 768 cmꢀ1; dH (300 MHz, CDCl3): 3.17 (2H,
d, J = 4.2 Hz, PhCH2), 3.73 (1H, dd, J = 6.3 Hz, 1.6 Hz, H-5), 4.41 (1H, t, J = 6.3 Hz,
H-5), 5.05 (1H, dd, J = 6.3 Hz, 1.6 Hz, H-4), 5.57 (1H, t, J = 4.2 Hz, H-2), 7.41–
7.40 (10H, m, aromatic protons). dC (75 MHz, CDCl3): 41.3 (PhCH2), 72.7 (C-5),
77.7 (C-4), 105.7 (C-2), 126.1 (C-200, C-600), 126.5 (C-400), 127.8 (C-10), 128.7 (C-
300, C-500), 128.5 (C-20, C-60), 130.2 (C-30, C-50), 136.4 (C-10), 139.1 (C-100). HRMS
(EI) found M+, 240.1641. C16H16O2 requires 240.1601. trans-5: Colourless gum;
mmax (KBr) 3057, 2937, 1579, 1427, 1257, 1128, 1024, 750 cmꢀ1; dH (300 MHz,
CDCl3): 3.36 (2H, d, J = 4.8 Hz, PhCH2), 3.73 (1H, dd, J = 7.8 Hz, 2.1 Hz, H-5), 4.35
(1H, t, J = 7.8 Hz, H-5), 5.35 (1H, dd, J = 7.8 Hz, 2.1 Hz, H-4), 5.42 (1H, t,
J = 4.8 Hz, H-2), 7.26–7.48 (8H, m, aromatic protons); dC (75 MHz, CDCl3): 37.9
(PhCH2), 71.1 (C-5), 75.0 (C-4), 103.9 (C-2), 126.8 (C-50), 127.0 (C-500), 127.2 (C-
40), 128.8 (C-30), 128.9 (C-300), 129.1 (C-600), 129.4 (C-60), 129.7 (C-400), 131.5 (C-
200), 133.8 (C-20), 133.9 (C-100), 138.1 (C-10). HRMS (EI) found M+, 309.0168.
C16H14O2Cl2 requires 309.0148. trans-7: White gum; mmax (KBr): 2923, 1569,
1427, 1247, 1134, 788, 746 cmꢀ1; dH (300 MHz, CDCl3): 3.60 (2H, d, J = 4.2,
PhCH2), 3.64 (1H, dd, J = 6.3 Hz, 1.5 Hz, H-5), 4.13 (1H, t, J = 6.3 Hz, H-5), 4.94
(1H, dd, J = 6.3 Hz, 1.5 Hz, H-4), 5.25 (1H, t, J = 4.2 Hz, H-2), 7.21–7.27 (8H, m,
aromatic protons); dC (75 MHz, CDCl3): 40.7 (PhCH2), 71.8 (C-5), 77.6 (C-4),
104.8 (C-2), 124.3 (C-600), 126.4 (C-60), 126.9 (C-40), 128.2 (C-20), 128.3 (C-200),
129.4 (C-400), 129.8 (C-500), 130.1 (C-50), 134.1 (C-300), 134.5 (C-30), 137.6 (C-100),
141.5 (C-10). HRMS (EI) found M+, 309.0183. C16H14O2Cl2 requires 309.0148.
trans-9: White Gum; mmax (KBr): 3076, 2846, 1587, 1479, 1271, 1215, 1095,
825, 727 cmꢀ1; dH (300 MHz, CDCl3): 3.09 (2H, d, J = 4.2 Hz, PhCH2), 3.63 (1H,
dd, J = 6.3 Hz, 1.5 Hz, H-5), 4.15 (1H, t, J = 6.9 Hz, H-5), 4.96 (1H, dd, J = 6.9 Hz,
1.5 Hz, H-4), 5.25 (1H, t, J = 4.2 Hz, H-2), 7.48 (4H, d, J = 8.4 Hz, aromatic
protons), 7.90 (4H, d, J = 8.4 Hz, aromatic protons); dC (75 MHz, CDCl3): 39.8
(PhCH2), 71.9 (C-5), 77.7 (C-4), 104.9 (C-2), 127.6 (C-300, C-500), 128.3 (C-30, C-
50), 128.7 (C-200, C-600), 131.3 (C-20, C-60), 12), 132.8 (C-400), 133.9 (C-40), 134.1
(C-10), 137.2 (C-100). HRMS (EI) found M+, 309.0168. C16H14O2Cl2 requires
309.0148. Compound 16: yellow gum; mmax (KBr): 2923, 2856, 1606, 1290,
1251, 1118, 1029 cmꢀ1; dH (300 MHz, CDCl3): 3.71 (6H, s, 2 ꢁ MeO), 3.81 (2H,
dd, J = 12.1 Hz, 3.9 Hz, H-3a, 6a), 3.94 (2H, dd, J = 12.1 Hz, 7.8 Hz, H-3b, 6b),
6.05 (2H, dd, J = 7.8 Hz, 3.9 Hz, H-2, 5), 6.83 (4H, d, J = 8.7 Hz, H-20, 60, 200, 600),
7.33 (4H, d, J = 8.7 Hz, H-30, 50, 300, 500); dC (75 MHz, CDCl3): 55.2 (2 ꢁ MeO), 65.5
(C-3, 6), 77.6 (C-2, 6), 114.1 (C-20, 60, 200, 600), 128.2 (30, 50, 300, 500), 129.1 (10, 100),
159.7 (40, 400). HRMS (EI) found M+, 300.1435. C18H20O4 requires 300.1362.
Compound 18: brown gum; mmax (KBr): 2914, 2829, 1593, 1456, 1247, 1134,
1020, 806, 746 cmꢀ1; dH (300 MHz, CDCl3): 3.82 (6H, s, 2 ꢁ MeO), 3.85 (6H, s,
2 ꢁ MeO), 3.87 (2H, s, H-3a, 6a), 4.00 (2H, dd, J = 12.1 Hz, 8.1 Hz, H-3b, 6b), 6.01
(2H, dd, J = 8.1 Hz, 3.9 Hz, H-2, 5), 6.81 (2H, d, J = 8.1 Hz, H-50, 500), 6.94 (2H, d,
J = 1.8 Hz, H-20, 200), 6.96 (2H, dd, J = 8.1 Hz, 1.8 Hz, H-60, 600); dC (75 MHz,
CDCl3): 55.8 (2 ꢁ MeO-40), 55.9 (2 ꢁ MeO-30), 65.6 (C-3, 6), 77.8 (C-2, 6), 110.1
(C-20, 200), 111.2 (C-50, 50), 119.2 (C-60, 600), 129.4 (10, 100), 148.9 (30, 300), 149.1
(40, 400). HRMS (EI) found M+, 360.1559. C20H24O6 requires 360.1573.
14. Concellon, J. M.; Bernad, P. L.; del Solar, V.; Garcia-Granda, S.; Diaz, M. R. Adv.
Synth. Catal. 2008, 350, 477.