Preparation of oxetanes by 4-endo trig electrophilic cyclisations of cinnamic alcohols

Article abstract of DOI:10.1016/S0040-4039(01)00226-X

The reaction of substituted cinnamic alcohols with bis(sym-collidine)bromine(I) hexafluorophosphate was examined. In general no oxetane was obtained when a substituent was fixed on the carbon-carbon double bond. However, oxetanes were formed in high yield

Full text of DOI:10.1016/S0040-4039(01)00226-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2477–2479
Preparation of oxetanes by 4-endo trig electrophilic cyclisations
of cinnamic alcohols
Se´bastien Albert, Sylvie Robin and Ge´rard Rousseau*
Laboratoire des Carbocycles (Associe´ au CNRS), Institut de Chimie Mole´culaire d’Orsay Baˆt. 420, Universite´ de Paris-Sud,
91405 Orsay, France
Received 15 November 2000; accepted 2 February 2001
Abstract—The reaction of substituted cinnamic alcohols with bis(sym-collidine)bromine(I) hexafluorophosphate was examined. In
general no oxetane was obtained when a substituent was fixed on the carbonꢀcarbon double bond. However, oxetanes were
formed in high yields when two substituents were present in a of the alcohol function. © 2001 Elsevier Science Ltd. All rights
reserved.
We have recently reported that oxetanes could be
obtained by cyclisation of cinnamyl alcohols using bis-
(collidine)bromine(I) hexafluorophosphate as electro-
phile.1 However, only the alcohol possessing a gem-
dimethyl group in a of the alcohol function led to the
oxetane in a satisfactory yield (Scheme 1).1 These
Table 1. Reaction of a- and b-substituted cinnamyl alcohols with bis(collidine)bromine(I) hexafluorophosphate
* Corresponding author. Fax: 33 1.69.15.62.78; e-mail: grousseau@icmo.u-psud.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00226-X

2478
S. Albert et al. / Tetrahedron Letters 42 (2001) 2477–2479
the scope of this electrophilic cyclisation. In a first
study, we examined the influence of a substituent fixed
on the carbonꢀcarbon double bond. The substrates
were prepared by conventional procedures. The cyclisa-
tions were carried out by addition of a methylene
chloride solution of bis(collidine)bromine(I) hexafluoro-
phosphate to the alcohols.3 Our results are reported in
Table 1.
Scheme 1.
No oxetane was obtained with a-substituted cinnamic
alcohols (entries a and b). Ketones formed by migra-
tion of a hydrogen (entry a) or a methyl (entry b) were
isolated. This kind of rearrangement of allylic alcohols
induced by an electrophile has some precedents in the
literature.4 Only the b-substituted cinnamic alcohol 1e
led to the oxetane 2e in moderate yield (entry e). Its
cyclisations occurred via a carbocationic interme-
diate.
Interest in oxetanes has increased rapidly, mainly in
organic synthesis and in industry (for example for the
formation of polymers);2 thus, we decided to investigate
Scheme 2.
Table 2. Reaction of cinnamyl alcohols with bis(collidine)bromine(I) hexafluorophosphate

S. Albert et al. / Tetrahedron Letters 42 (2001) 2477–2479
2479
Scheme 3.
stereochemistry was easily deduced from its NMR spec-
tra,5 and by a NOESY experiment.
stirring for 30 min, the solvent was removed and the residue
purified by chromatography over silica gel (hexane/ether).
4. (a) Brueckner, K.; Irmschen, K.; Werder, F. V.; Bork,
K.-H.; Metz, H. Chem. Ber. 1961, 94, 2897–2909; (b)
Bodrikov, I. V.; Kartashov, V. R.; Temnikova, T. I. J. Org.
Chem. (USSR) Engl. Trans. 1968, 4, 1286–1293; (c) Thomp-
son, H. W.; Muccino, R. R.; Trubelhorn, M. T. J. Org.
Chem. 1972, 37, 3531–3536; (d) Schneider, G.; Wolfling, J.;
Mesko, E.; Dombi, G. Steroids 1988, 51, 317–328.
Since the presence of a substituent on the carbonꢀcarbon
double bond was detrimental to the formation of oxe-
tanes, we decided to examine the cyclisation of com-
pounds only substituted in a of the alcohol function.
These alcohols were obtained in two steps by addition
of phenylacetylide lithium to carbonyl compounds, fol-
lowed by reduction of the carbonꢀcarbon triple bond
(Scheme 2).
5. Selected data: (2S*,3S*,4R*)-3-Bromo-2,4-dimethyl-2,4-
diphenyloxetane: 1H NMR (200 MHz, CDCl3); 2.24 (s, 6H);
4.50 (s, 1H); 7.20–7.59 (m, 10H). 13C NMR 19.6; 66.6; 105.4;
125.9; 127.8; 128.8; 141.4. (2S*,3S*,4R*)-3-Bromo-2-
The subsequent reactions with bis(collidine)bromine(I)
hexafluorophosphate were conducted as reported
above.3 Our results are reported in Table 2. The struc-
tures of the products were established from their spectral
data,5 and their stereochemistries were established by
NOESY experiments. Secondary alcohols (entries a and
b) led mainly to degradation; oxetanes were only
obtained in low yields. Only the tertiary alcohols (entries
c–f) led to oxetanes in good to high yields. When the two
substituents in a of the alcohol function were different
(entries f–h) a mixture of two diastereomers was
obtained. With the acetylenic alcohol (entry h) we
observed a competition between the cyclisation and
migration of the phenylethynyl group.
1
methyl-4-phenyloxetane: H NMR 1.53 (d, J=6 Hz, 3H);
4.17 (t, J=7 Hz, 1H); 5.03 (q, J=6 Hz, 1H); 5.70 (d, J=7
Hz, 1H); 7.28–7.57 (m, 5H). 13C NMR 21.2; 49.1; 83.5; 87.3;
125.4; 128.7; 128.8; 134.0. (2S*,3S*,4R*)-3-Bromo-2,4-
1
diphenyloxetane. H NMR 4.47 (t, J=8 Hz, 1H); 5.35 (d,
J=8 Hz, 2H); 7.40–7.67 (m, 10H). 13C NMR 50.0; 87.0;
125.6; 128.7; 128.9; 139.1. (2R*,3S*,4R*)-3-Bromo-2,4-
1
diphenyloxetane. H NMR 5.05 (dd, J=6 and 7 Hz, 1H);
5.95 (d, J=6 Hz, 1H); 6.06 (d, J=7 Hz, 1H); 7.30–7.70 (m,
10H). 13C NMR 50.5; 82.9; 89.9; 127.6; 128.0; 128.2; 128.3;
128.4; 128.8; 138.4; 139.7. (2S*,3S*)-3-Bromo-2-phenyl-1-
oxaspiro[3.5]nonane: 1H NMR 1.24–2.25 (m, 10H); 4.32 (d,
J=7 Hz, 1H); 5.62 (d, J=7 Hz, 1H); 7.22–7.50 (m, 5H). 13
C
NMR 21.9; 22.1; 25.0; 34.2; 38.9; 54.7; 85.3; 85.5; 125.3;
We also examined the oxidative cleavage of the phenyl
groups. For example, reaction of 3-bromo-2,2-dimethyl-
4-phenyl oxetane 1 with NaIO4 in the presence of a
catalytic amount of ruthenium(III) chloride led to the
desired acid 2 in excellent yield (Scheme 3). These results
allow the preparation of oxetin derivatives. Oxetin (oxe-
tan-2-carboxylic acid) was reported to be a natural
product possessing antibiotic activities.6
128.5; 128.6; 140.1. (2S*,3S*)-3-Bromo-2,2-di-butyl-4-
phenyloxetane: H NMR 0.80–2.20 (m, 18H); 4.42 (d, J=7
1
Hz, 1H); 5.59 (d, J=7 Hz, 1H); 7.10–7.50 (m, 5H). 13C
NMR 13.9; 14.1; 23.0; 23.1; 24.8; 25.0; 34.3; 38.9; 54.0; 85.3;
87.9; 125.2; 128.5; 128.7; 139.9. (2S*,3S*)-3-Bromo-2-
methyl-2-pentyl-4-phenyloxetane. Major diastereomer: 1H
NMR 1.25–1.95 (m, 14H); 4.39 (d, J=7 Hz, 1H); 5.61 (d,
J=7 Hz, 1H); 7.20–7.55 (m, 5H). 13C NMR 13.9; 22.5; 22.6;
22.7; 31.9; 37.4; 53.2; 85.0; 86.5; 125.2; 128.5; 128.5; 139.8.
Minor diastereomer: 1H NMR 1.25–1.95 (m, 14H); 4.41 (d,
In conclusion we report that oxetanes can be obtained
in good yields from cinnamyl alcohols using bis(col-
lidine)bromine(I) hexafluorophosphate as electrophile.
Their transformation into oxetin derivatives is under
investigation.
J=7 Hz, 1H); 5.58 (d, J=7 Hz, 1H); 7.20–7.55 (m, 5H). 13
C
NMR 13.9; 22.6; 22.9; 26.3; 32.1; 37.4; 55.3; 85.0; 85.7;
125.2; 128.3; 128.4; 139.8. (2S*,3S*)-3-Bromo-2-methyl-4-
phenyl-2-phenylethynyloxetane. Minor diastereomer: 1H
NMR 1.98 (s, 3H); 4.90 (d, J=8 Hz, 1H); 5.61 (d, J=8 Hz,
1H); 7.10–7.41 (m, 10H). Major diastereomer: 1H NMR
1.90 (s, 3H); 4.52 (d, J=8 Hz, 1H); 5.81 (d, J=8 Hz, 1H);
7.28–7.65 (m, 10H). 13C NMR 28.6; 53.3; 81.0; 86.3; 87.5;
90.3; 122.2; 125.5; 128.3; 128.7; 128.8; 128.9; 132.0; 138.9.
3-(Bromophenylmethyl)-5-phenyl-pent-4-yn-2-one: 1H NMR
2.49 (s, 3H); 3.35 (d, J=9.5 Hz, 1H); 4.46 (d, J=9.5 Hz,
1H); 7.25–7.50 (m, 10H). 13C NMR 26.6; 41.5; 56.7; 86.2;
86.6; 122.7; 128.0; 128.2; 128.5; 128.6; 128.6; 137.2; 200.2.
6. Bach, T.; Schro¨der, J. Liebigs Ann./Recueil 1997, 2265–2267.
7. Homsi, F.; Robin, S.; Rousseau, G. Org. Synth. 2000, 77,
206–211.
References
1. Homsi, F.; Rousseau, G. J. Org. Chem. 1999, 64, 81–85.
2. See for example: Searles, S. In Comprehensive Heterocyclic
Chemistry; Katrisky, A. R.; Rees, C. W., Eds.; Pergamon
Press: New York, 1984; Vol. 7 pp. 363–402.
3. General procedure: To a solution of alcohol (2 mmol) in
methylene chloride (20 mL) was added over 6 h at rt a
methylene chloride solution (60 mL) of bis(col-
lidine)bromine(I) hexafluorophosphate (2.6 mmol).7 After
.