4-endo-trig cyclization processes using bis(collidine)bromine(i) hexafluorophosphate as reagent: Preparation of 2-oxetanones, 2-azetidinones, and oxetanes

Article abstract of DOI:10.1021/jo9810361

Reaction in methylene chloride of bis(collidine)bromine(I) hexafluorophosphate with α,β-unsaturated acids and α,β-unsaturated N- sulfonamides was found to lead diastereospecifically to the corresponding 2- oxetanones and 2-azetidinones in moderate yields (23-60%), by an almost unknown 4-endo cyclization. This process allow the synthesis of these interesting classes of products in one step from common substrates. Similarly, the reaction of cinnamic alcohols led, by the same cyclization procedure, to oxetanes (20-36%); the presence of a gem-dimethyl group in α of the alcohol function appeared beneficial.

Full text of DOI:10.1021/jo9810361

J . Org. Chem. 1999, 64, 81-85
81
4-En d o-Tr ig Cycliza tion P r ocesses Usin g Bis(collid in e)br om in e(I)
Hexa flu or op h osp h a te a s Rea gen t: P r ep a r a tion of 2-Oxeta n on es,
2-Azetid in on es, a n d Oxeta n es
Fadi Homsi 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 J une 1, 1998
Reaction in methylene chloride of bis(collidine)bromine(I) hexafluorophosphate with R,â-unsaturated
acids and R,â-unsaturated N-sulfonamides was found to lead diastereospecifically to the corre-
sponding 2-oxetanones and 2-azetidinones in moderate yields (23-60%), by an almost unknown
4-endo cyclization. This process allow the synthesis of these interesting classes of products in one
step from common substrates. Similarly, the reaction of cinnamic alcohols led, by the same
cyclization procedure, to oxetanes (20-36%); the presence of a gem-dimethyl group in R of the alcohol
function appeared beneficial.
Sch em e 1
The preparation of small ring compounds by electro-
philic cyclizations has mainly been reported for the
preparation of epoxides and 2-oxetanones.1 The obtention
of epoxides by electrophilic addition of halogens on the
carbon-carbon double bond of allylic alcohols was first
published 60 years ago2 and since then extensively
studied.3 The preparation of 2-oxetanones by cyclization
of 3-butenoic acids was observed by Barnett in the 1970s4
and then applied in organic synthesis.3i,5 Likewise, since
the initial report by Magnus,6 the preparation of oxetanes
by electrophilic cyclization of homoallylic alcohols was
reported.3i,7 While less studied, the formation of nitrogen
heterocycles such as aziridines,8 azetidines,9 and â-lac-
tames 10 were also published. All these electrophilic ring
closures occur by exo-mode cyclizations and are, as
noticed by Baldwin,11 favored processes (Scheme 1).
Contrary to these well-known cyclizations, the forma-
tion of four-membered ring compounds by an endo-trig
Sch em e 2
process (Scheme 2) is less common. Bartlett, 60 years ago,
reported that reaction of bromine with the sodium salt
of dimethylsuccinic acid led to an oxetanone.12 Subse-
quently, similar results were obtained with cinnamic acid
derivatives13 and more recently with some R,â-unsatur-
ated acids in the presence of calcium hypochlorite.14
Formation of an oxetane by reaction of iodine with an
allylic alcohol was also reported.3e These four-membered
heterocycles were generally obtained with low yields.
These results can be explained by the high strain in the
transition state.
(1) (a) Dowle, M. D.; Davies, D. I. Chem. Soc. Rev. 1979, 171. (b)
Harding, K. E.; Tiner, T. H. In Comprehensive Organic Synthesis; Trost,
B. M., Ed.; Pergamon Press: New York, 1991; Vol. 4, p 363.
(2) Straus, F.; Ku¨hnel, R. Chem. Ber. 1933, 66, 1834.
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(b) Lindgren, B. O.; Svahn, C. M. Acta Chem. Scand. 1970, 24, 2699.
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6, 15. (d) Barelli, L.; Bellucci, G.; Berti, C.; Golfarini, M.; Marioni, F.;
Scartoni, V. Gazz. Chim. Ital. 1974, 104, 107. (e) Diner, U. E.; Worsley,
M.; Lown, J . W. J . Chem. Soc. C 1971, 3131. (f) Ganem, B. J . Am.
Chem. Soc. 1976, 98, 858. (g) Santelli, M.; Viala, J . Tetrahedron Lett.
1977, 4397. (h) Midland, M. M.; Halterman, R. L. J . Org. Chem. 1981,
46, 1227. (i) Evans, R. D.; Magee, J . W.; Schauble, J . H. Synthesis 1988,
862.
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(b) Barnett, W. E.; McKenna, J . C. J . Chem. Soc., Chem. Commun.
1971, 551. (c) Barnett, W. E.; Sohn, W. E. J . Chem. Soc., Chem.
Commun. 1972, 472. (d) Barnett, W. E.; Sohn, W. H. Tetrahedron Lett.
1972, 1777. (e) Barnett, W. E.; Needham, L. L. J . Org. Chem. 1975,
40, 2843.
Rea ction of r,â-Un sa tu r a ted Acid s. As part of our
research on the preparation of medium ring compounds,15
(6) Ehlinger, E.; Magnus, P. J . Am. Chem. Soc. 1980, 102, 5005.
(7) (a) Manabe, S.; Nishino, C. Tetrahedron 1986, 42, 3461. (b)
Brown, W. L.; Fallis, A. G. Can. J . Chem. 1987, 65, 1828. (c) Arjona,
O.; Fernandez de la Pradilla, R.; Plumet, J .; Viso, A. Tetrahedron 1989,
42, 4565. (d) Arjona, O.; Fernandez de la Pradilla, R.; Plumet, J .; Viso,
A. J . Org. Chem. 1992, 57, 774. (e) Galatsis, P.; Parks, D. J .
Tetrahedron Lett. 1994, 37, 6611. (f) Galatsis, P.; Millan, S. D.; Nechala,
P.; Ferguson, G. J . Org. Chem. 1994, 59, 6643. (g) J ung, M. E.; Nichols,
C. J . Tetrahedron Lett. 1996, 37, 7667.
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38, 8371.
(5) (a) Cambie, R. C.; Hayward, R. C.; Roberts, J . L.; Rutledge, P.
S. J . Chem. Soc., Perkin Trans 1 1974, 1864. (b) Holbert, G. W.; Weiss,
L. B.; Ganem, B. Tetrahedron Lett. 1976, 4435. (c) Nicolaou, K. C.;
Lysenko, Z. J . Am. Chem. Soc. 1977, 99, 3185. (d) Cook, C. H.; Cho, Y.
S.; J ew. S. S.; Suh, Y. G.; Kang, E. K. Arch. Pharmacal. Res. 1983, 6,
45. (e) Cambie, R. C.; Rutledge, P. S.; Somerville, R. F.; Woodgate, P.
D. Synthesis 1988, 1009. (f) Shibata, I.; Toyata, M.; Baba, A.; Matsuda,
H. J . Org. Chem. 1990, 55, 2487. (g) Askani, R.; Keller, U. Liebigs Ann.
Chem. 1988, 61. (h) Sutherland, J . K.; Watkins, W. J .; Bailey, J . P.;
Chapman, A. K.; Davies, G. M. J . Chem. Soc., Chem. Commun. 1989,
1386. (i) Gore, V. G.; Narasimham, N. S. Indian J . Chem., Sect. B.
1991, 30, 241. (j) Black, T. H.; Huang, J . Tetrahedron Lett. 1993, 34,
1411. (k) Mead, K. T.; Park, M. Tetrahedron Lett. 1995, 36, 1205.
(9) (a) Corey, E. J .; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.;
Sarshar, S. J . Org. Chem. 1993, 58, 5600. (b) Berthe, B.; Duturquin,
F.; Paulmier, C. Tetrahedron Lett. 1997, 38, 1393.
(10) (a) Biloski, A. J .; Wood, R. D.; Ganem, B. J . Am. Chem. Soc.
1982, 104, 3233. (b) Rajendra, G.; Miller, M. J . Tetrahedron Lett. 1985,
26, 5385. (c) Rajendra, G.; Miller, M. J . J . Org. Chem. 1987, 52, 4471.
(d) Rajendra, G.; Miller, M. J . Tetrahedron Lett. 1987, 28, 6257. (e)
Knapp, S.; Levorse, A. J . Org. Chem. 1988, 53, 4006.
(11) Baldwin, J . E. J . Chem. Soc., Chem. Commun. 1976, 734.
(12) Tarbell, D. S.; Bartlett, P. D. J . Am. Chem. Soc. 1937, 59, 408.
(13) (a) Price, C. C.; Blunt, H. W. J . Org. Chem. 1969, 34, 2484. (b)
Kingsburry, C. A.; Max, G. J . Org. Chem. 1978, 43, 3131.
(14) Solas, D.; Wolinsky, J . Synth. Commun. 1981, 11, 609.
10.1021/jo9810361 CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/11/1998

82 J . Org. Chem., Vol. 64, No. 1, 1999
Homsi and Rousseau
Ta ble 1. Rea ction of r,â-Un sa tu r a ted Acid s w ith
stereoisomer (entries f and h), while the 50:50 E/Z mix-
ture of these acids (entries e and g) led to a 50:50 mixture
of diastereoisomers. These results show that the cycliza-
tions are diastereospecific. The same result was obtained
with acid 1i, for which only one diastereoisomer was iso-
lated. The anti addition of the bromine atom and the oxy-
gen atom of the carboxylate on the carbon-carbon double
bond conducts us to propose the structures indicated in
Table 1. These results were confirmed in the case of the
diastereoisomeric lactones 2g in NMR by a NOESY ex-
periment. Comportment of the â-phenyl propenoic acids
1g-j appeared interesting; when these acids are substi-
tuted in R, we mainly observed the formation of oxetan-
2-ones, while with cinnamic acid 1j, only electrophilic
decarboxylation was observed (evolution of carbon dioxide
was observed as soon as the reagent was added). This
decarboxylation reaction was also diastereospecific since
E-bromostyrene (E/Z g 98:2) was obtained quatitatively.
These results can be explained by the formation of an
intermediate bromonium, which can follow different
pathways depending of the degree of stabilization of the
positive charge developed on the carbon â to the acid
function (Scheme 4). When one alkyl group is present,
the stabilization is insufficient to allow the formation of
the â-lactone; the polymers observed could result from
either the evolution of an instable R-lactone16 (obtained
by a favored 3-exo-trig-mode cyclization) or the evolution
of an ionic intermediate.13b With two alkyl groups in â of
the acid function, the stabilization of the charge appears
enough to allow the 4-endo-mode cyclization. With cinnam-
ic acid 1j, the positive charge developed on C3 weakened
the C1-C2 bond and conducted to a carbon dioxide elimi-
nation. Similar electrophilic decarboxylations with cin-
namic acid derivatives have been reported.17 Surpris-
ingly, chloronium addition on the carbon-carbon double
bond of cinnamic acid did not lead to the chlorostyrene
but instead to the oxetan-2-one in very low yield.14 Final-
ly, introduction of substituents at C2 on the cinnamic
framework diminished the positive charge on C3, and the
4-endo-mode cyclization was again observed (entries g-i).
Examples of isomerization of â-lactones into γ-lactones
are reported in the literature4c-d,5a,c,f,j,18 (Scheme 5). So
it is possible to wonder whether our 4-endo-lactones were
not formed from the isomerization of the 3-exo-lactones.
Some arguments can be advanced against this hypoth-
esis. In the 4 f 5 ring enlargements known, the isomer-
ization occurred slowly enough to be experimentally de-
tected. In our case, this isomerization must have occurred
with a very fast reaction rate since R-lactones are known
to be highly instable compounds,16 leading to polymers
in solution even at very low temperature. The second ar-
gument is the generality of the 4-endo cylization, which
was observed also for the formation of â-lactams and oxe-
tanes (vide infra), for which this ring expansion seems
unlikely.
Biscollid in ebor m in e(I) Hexa flu or op h osp h a te
a
Also, 10% of the vinyl bromide formed by decarboxylation of
the acid was isolated.
Sch em e 3
we were induced to study the reactivity of R,â-unsatur-
ated acids with bis(collidine)bromine(I) hexafluorophos-
phate. The acids used were either commercially available
or easily prepared by standard methods. After optimiza-
tion, the reactions were carried out in methylene chloride,
at room temperature, and in the presence of 1 equiv of
collidine. Our results are reported Table 1. As our results
show, the yields in â-lactones depend on the substitution
at the â-position of the carbon-carbon double bond. With
2-octenoic acid (entry a), only polymeric materials were
formed. With the â-dialkyl-substituted acids 1b-f, the
formation of 2-oxetanones and vinyl bromides were
always observed in moderate yields (Scheme 3). Oxetan-
2-ones 2b-i were characterized from their 1H and 13C
NMR and IR spectra; in particular, with IR, the νCO at
1840-1850 was always present. The vinyl bromides are
all known products. The low yield observed with 3,3-
dimethylacrylic acid, compared to the other â-dialkylacids
was attributed to the volality of the product.
Rea ction of r,â-Un sa tu r a ted Am id es. The encour-
aging results obtained with the R,â-unsaturated acids led
us to study the cyclization of R,â-unsaturated amides.
Since no cyclization was observed with 3-methylbut-2-
(15) Homsi, F.; Rousseau, G. J . Org. Chem. 1998, 63, 5255.
(16) Wierlacher, S.; Sander, W.; Liu, M. T. H. J . Org. Chem. 1992,
57, 1051 and references therein.
(17) (a) Graven, A.; J orgensen, K. A.; Dahl, S.; Stanczak, A. J . Org.
Chem. 1994, 59, 3543. (b) Naskar, D.; Chowdhury, S.; Roy, S.
Tetrahedron Lett. 1998, 39, 699.
Cyclizations of (Z)-3-methylocten-2-oic acid 1f and (E)-
3-phenyl-2-methylpropenoic acid 1h led only to one dia-
(18) Black, T. H.; McDermott, T. S. J . Chem. Soc., Chem. Commun.
1991, 184.

Preparation of 2-Oxetanones, 2-Azetidinones, and Oxetanes
Sch em e 4
J . Org. Chem., Vol. 64, No. 1, 1999 83
Sch em e 5
Sch em e 6
Ta ble 2. Rea ction of r,â-Un sa tu r a ted Am id es w ith
the 3,3-dimethylacrylic amides 3b and 3d . Again, we can
explain the formation of these â-lactams by a diaste-
reospecific 4-endo cyclization. These results are important
since they can allow a faster and easier synthesis of
substiuted â-lactams, which are known to be useful
compounds with potential applications as â-lactamases
or inhibitors of 3-hydroxy-3-methyl glutarate coenzyme
A synthase, human leukocyte elastase, poliovirus, and
human rhinovirus C3-proteinase.20
Biscollid in ebr om in e(I) Hexa flu or op h osp h a te
Rea ction of Allylic Alcoh ols. The reaction of allylic
alcohols with bis(collidine)iodine(I) perchlorate has been
reported to lead to epoxide or dioxanes.3i Similar results
were obtained with bis(collidine)bromine(I) hexafluoro-
phosphate.21 To observe formation of oxetanes by elec-
trophilic cyclization of allylic alcohols it appeared nec-
essary to introduce substituents in the position γ to the
alcohol function, which can stabilized the charge devel-
oped during the bromonium addition (Scheme 6). Our
results are reported in Table 3.
The alcohols studied were either commercially avail-
able or prepared by reduction from the corresponding R,â-
unsaturated esters. The products were characterized
from their spectroscopic data. The low yields observed
for these cyclizations were due to the formation of tar
materials and unidentified products. Only the alcohols
substituted by an aryl group in the â position led to the
oxetanes. With cyclohexylidene ethanol (entry a), the
electronic effect of the cyclohexane ring appeared enough
to stabilize the charge; however, the 4-endo product was
not isolated due to an easy in situ formation of homoal-
lylic alcohol, which after a second addition of bis(colli-
dine)bromine(I) hexafluorophosphate, led to product 6a
of unknown stereochemistry (Scheme 7).
enoic acid amide, we decided to introduced a p-substi-
tuted phenylsulfonic group on the nitrogen to increase
its acidity. The desired amides were prepared by reaction
of the acid chlorides with the corresponding sulfonamines
(25-50%). The modest yields are due to the low reactivity
of the sulfonamines. The cyclization reactions were car-
ried out in methylene chloride at room temperature in
the presence of 1.3 equiv of bis(collidine)bromine(I) hexa-
fluorophosphate. Our results are reported in Table 2.
The â-lactams were characterized by 1H and 13C NMR
and IR spectroscopy. No defined product was observed
with the amide 3a . Monosubtituted amides 3c and 3e
led to only one diastereoisomer in which the two hydro-
gens were postulated to be trans on the basis of an anti
addition of the bromine and nitrogen atoms on the
carbon-carbon double bond. The 1H NMR coupling
constant for H3-H4 (1.5 Hz) appears compatible with this
assumption.19 Satisfactory yields were also obtained for
(19) (a) Nelson, O. A. J . Org. Chem. 1972, 37, 1447. (b) Casadei, M.
A.; Inesi, A.; Moracci, F. M.; Occhialini, D. Tetrahedron 1989, 45, 6885.
(20) (a) Firestone, R. A.; Barker, P. L.; Pisano, J . M.; Ashe, B. M.;
Dahlgren, M. E. Tetrahedron 1990, 46, 2255. (b) Skiles, J . W.; McNeil,
D. Tetrahedron Lett. 1990, 31, 7277. (c) Thompson, K. L.; Chang, M.
N.; Chiang, Y. C. P.; Yang, S. S.; Chabala, J . C.; Ariston, B. H.;
Greenspan. M. D.; Hanf, D. P.; Yudkovitz, J . Tetrahedron Lett. 1991,
32, 3337. (d) Singh, R.; Cooper, R. D. G. Tetrahedron 1994, 50, 12049.
(e) Han, W. T.; Trehan, A. K.; Wright, J . J . K.; Federici, M. E.; Seiler,
S. M.; Meanwell, N. A. Bioorg. Med. Chem. 1995, 3, 1123.
(21) Rousseau, G. Unpublished results.

84 J . Org. Chem., Vol. 64, No. 1, 1999
Homsi and Rousseau
Ta ble 3. Rea ction of Allylic Alcoh ols w ith
Biscollid in ebr om in e(I) Hexa flu or op h osp h a te
necessary to explain the results observed with the (Z)-
cinnamic alcohol. These 4-endo cyclizations were not
observed with bis(collidine)iodine(I) hexafluorophosphate
(polymeric compounds were formed). We are not able at
present to explain this difference in reactivity. Work is
in progress to improve these highly unfavorable cycliza-
tions with great potential in organic synthesis.
Exp er im en ta l Section
Gen er a l Rem a r k s. All NMR spectra were measured in
CDCl3, and chemical shifts are expressed in ppm relative to
internal CHCl3. All solvents were purified by known standard
procedures; in particular, methylene chloride was distilled
1
from CaH2. H NMR spectra were measured in CDCl3 at 200
or 250 MHz. The preparation of bis(collidine)bromine(I) hexaflu-
orophosphate was previously reported.15 2-Octenoic acid, 3,3-
dimethylacrylic acid, cinnamic acid, R-methylcinnamic acid,
and R-phenylcinnamic acid are commercially available. Cy-
clohexylideneacetic acid, (E,Z)-3-methyl-2-octenoic acid, and
3-butyl-2-heptenoic acid were prepared in two steps by reaction
of the corresponding ketone with methyl(triphenylphospho-
ranylidene)acetate followed by saponification of the ester
function. Stereochemically pure methyl (Z)-3-butyl-2-hep-
tenoate was obtained by preparative thin-layer chromatogra-
phy (hexanes/ethyl acetate, 90:10). Its saponification led then
to (Z)-3-butyl-2-heptenoic acid. The 50:50 mixture of (E/Z)-2-
methyl-3-phenylacrylic acid was prepared by irradiation of (E)-
2-methyl-3-phenylacrylic acid in benzene. The different acid
chlorides were prepared by reaction of the different acids with
oxalyl chloride. Allylic alcohols were commercially available
or prepared by reduction of the corresponding esters.
3-Bu tyl-2-h ep ten oic Acid .23 1H NMR: δ 0.85-0.95 (t, J
) 6.0, 6H); 1.25-1.50 (m, 8H); 2.10-2.20 (t, J ) 7.5 Hz, 2H);
2.55-2.65 (t, J ) 7.5 Hz, 2H); 5.65 (s, 1H); 12.0-12.5 (m, 1H).
(E)-3-Meth yl-2-octen oic Acid .24 1H NMR: δ 0.85-0.92 (t,
J ) 7 Hz, 3H); 1.20-1.50 (m, 6H); 2.15 (d, J ) 1 Hz, 3H); 2.10-
2.20 (t, J ) 7 Hz); 5.7 (m, 1H); 12.0-12.5 (m, 1H).
Sch em e 7
(Z)-3-Meth yl-2-octen oic Acid .25 1H NMR: δ 0.82-1.95 (t,
J ) 7 Hz); 1.20-1.55 (m, 6H); 1.90 (d, J ) 1 Hz, 3H); 2.55-
2.70 (t, J ) 7 Hz, 2H); 5.68 (s, 1H); 12.0-12.5 (m, 1H).
Gen er a l P r oced u r e for th e P r ep a r a tion of Oxeta n -2-
on es. To bis(collidine)bromine(I) hexafluorophosphate (0.87
g, 1.87 mmol) in methylene chloride (20 mL), was added
over a period of 15 min a solution of the acid 1 (1.4 mmol)
and collidine (0.19 g, 1.6 mmol) in methylene chloride (10
mL). After 1h, silica gel was added (2 g) and the solvent
was removed. The products were purified by flash chromatog-
raphy (hexane/ethyl acetate, 90:10) to give the vinyl bromide
and the oxetan-2-one 2. The different results are reported
Table 1.
3-Br om o-4,4-d im eth yloxeta n -2-on e, 2b. 1H NMR: δ 1.69
(s, 3H); 1.71 (s, 3H); 4.96 (s, 1H). 13C NMR: δ 24.34; 26.18;
50.23; 81.42; 164.40. IR (neat): 1840 cm-1 (γ CO). Anal. Calcd
for C5H7O2Br: C, 33.55; H, 3.94. Found: C, 33.70; H, 4.03.
3-Br om o-4,4-d ibu tyloxeta n -2-on e, 2c. 1H NMR: δ 0.85-
1.00 (t, J ) 6.0 Hz, 6H); 1.22-1.50 (m, 8H); 2.70-2.10 (m, 4H);
4.95 (s, 1H). 13C NMR: δ 13.77; 13.81; 22.59 (2C); 25.46; 25.87;
33.91; 35.84; 49.45; 85.20; 165.10. IR (neat): 1840 cm-1 (γ CO).
Anal. Calcd for C11H19O2Br: C, 50.20; H, 7.28. Found: C, 50.27;
H, 7.36.
Cinnamic alcohol led to trans-3-bromo-2-phenyloxet-
ane. The stereochemistry was deduced from its H NMR
1
spectra. In particular, the coupling constant between H2
and H3 was found to be 6 Hz. This value appears to be
characteristic of a trans coupling constant, since a higher
value would be expected for a cis coupling constant.22 The
cis isomer of cinnamic alcohol led to the same oxetane.
This result means that cyclizations of alcohols occur
under thermodynamic control. The carbocationic char-
acter of the intermediate is probably more developed in
this case than with the formations of oxetanones and
azetidinones. This is the consequence of the less favored
geometry for the cyclization of this kind of substrates
compare to the cyclization of the acids and the amides.
The presence of a gem-dimethyl group (entry f) was found
to have a benefical influence since the yield in oxetane
6f was notably increased compared with the yield ob-
tained for the oxetane 6b.
In conclusion, we have shown that the 4-endo cycliza-
tions are possible and can be a convenient way to prepare
2-oxetanones, 2-azetidinones, and oxetanes in one step
from linear substrates. The mechanism of these cycliza-
tions is not as yet clear. Indeed, two possibilities can be
considered: a direct cyclization from the intermediate
bromonium or evolution of the bromonium to a carboca-
tionic intermediate, followed by cyclization. The direct
reaction of the bromonium intermediate, while sterically
highly difficult, can be used to explain the results ob-
served with the R,â-ethylenic acids and amides, since
these reactions appeared diastereospecific. With allylic
alcohols, the presence of a carbocationic intermediate is
3-Br om o-1-oxa sp ir o[3.5]n on a n -2-on e, 2d . 1H NMR: δ
1.35-2.05 (m, 10H); 4.82 (s, 1H). 13C NMR: δ 22.52; 22.90;
24.20; 33.06; 35.81; 49.67; 82.99; 165.03. IR (neat): 1840 cm-1
(γ CO). Anal. Calcd for C8H11O2Br: C, 43.86; H, 5.06. Found:
C, 43.77; H, 5.20.
(22) Balsamo, G.; Ceccarelli, G.; Crotti, P.; Macchia, F. J . Org. Chem.
1975, 40, 473.
(23) Normant, J . F.; Cahiez, G.; Chuit, C.; Villieras, J . J . Organomet.
Chem. 1974, 77, 281.
(24) Ogura, K.; Nishino, T.; Koyama, T.; Seto, S. J . Am. Chem. Soc.
1970, 92, 6036.
(25) Sliwa, H.; Maitte, P. Bull. Soc. Chim. Fr. 1962, 369.

Preparation of 2-Oxetanones, 2-Azetidinones, and Oxetanes
J . Org. Chem., Vol. 64, No. 1, 1999 85
3-Br om o-4-m eth yl-4-p en tyloxeta n -2-on es, 2e-f. From
(E)-3-Methyl-2-octenoic acid. 1H NMR: δ 0.85-0.92 (t, J ) 7.5
Hz, 3H); 1.22-1.50 (m, 6H); 1.65 (s, 3H); 1.75-2.10 (m, 2H);
4.95 (s, 1H). 13C NMR: δ 13.74; 23.28; 23.41; 23.70; 31.39;
39.08; 49.21; 83.63; 164.68. IR (neat): 1840 cm-1 (γ CO). From
(Z)-3-Methyl-2-octenoic acid. 1H NMR: δ 0.85-1.00 (t, J ) 7.5
Hz, 3H); 1.25-1.50 (m, 6H); 1.68 (s, 3H); 1.86-2.00 (q, J )
10.0 Hz, 2H); 4.95 (s, 1H). 13C NMR: δ 13.90; 22.38; 23.52 (2C);
31.63; 36.92; 50.58; 83.10; 164.80. IR (neat): 1840 cm-1 (γ CO).
Anal. Calcd for C9H15O2Br: C, 45.95; H, 6.43. Found: C, 45.79;
H, 6.29.
was removed. The product was purified by flash chromatog-
raphy (85:15, pentane/ethyl acetate). The different results are
reported Table 2.
3-Br om o-4,4-d im et h yl-1-(4-m et h ylb en zen esu lfon yl)-
a zetid in -2-on e, 4b. White solid. mp 87-91 °C. 1H NMR: δ
1.60 (s, 3H); 1.75 (s, 3H); 2.44 (s, 3H); 2.46 (s, 3H); 4.65 (s,
1H); 7.35 (d, J ) 7.5 Hz, 2H); 7.90 (d, J ) 7.5 Hz, 2H). 13C
NMR δ 21.67; 23.91; 26.01; 53.64; 67.67; 127.36 (2C); 130.02
(2C); 136.23; 145.61; 160.12. IR (neat): 1820 cm-1 (γ CO). Anal.
Calcd for C12H14BrNO3S: C, 43.39; H, 4.25; N, 4.25. Found:
C, 42.98; H, 4.24; N, 3.85.
3-Br om o-3-m eth yl-4-p h en yloxeta n -2-on es, 2g-h . From
(E)-2-Methyl-3-phenylacrylic acid. 1H NMR: δ 1.52 (s, 3H);
5.89 (s, 1H); 7.30-7.52 (m, 5H). 13C NMR: δ 21.51; 60.35;
85.79; 125.26 (2C); 127.54 (2C); 129.45; 132.84; 167.52. IR
(neat): 1855 cm-1 (γ CO). Anal. Calcd for C10H9O2Br: C, 49.82;
H, 3.76. Found: C, 49.71; H, 3.93. From (Z)-2-Methyl-3-phen-
ylacrylic acid. 1H NMR: δ 2.32 (s, 3H); 5.45 (s, 1H); 7.27-
7.50 (m, 5H). 13C NMR: δ 25.51; 56.26; 83.51; 125.74; 128.36;
128.94; 129.10; 129.70; 134.60; 167.62. IR (neat): 1840 cm-1
(γ CO).
3-Br om o-1-(4-m eth ylben zen esu lfon yl)-4-p h en yla zeti-
d in -2-on e, 4c. White solid. mp 125-129 °C. H NMR: δ 2.45
1
(s, 3H); 4.60 (d, J ) 1.25 Hz, 1H); 5.05 (d, J ) 1.25 Hz, 1H);
7.20-7.40 (m, 7H); 7.65 (d, J ) 8.1 Hz, 2H).13C NMR: δ 21.66;
48.23; 67.83; 126.50 (2C); 127.54 (2C); 129.03 (2C); 129.71;
129.91 (2C); 133.91; 134.57; 145.79; 160.30. IR (neat): 1820
cm-1 (γ CO). Anal. Calcd for C15H13BrNO3S: C, 50.54; H, 3.71;
N, 3.68. Found: C, 50.28; H, 3.87; N, 3.51.
3-Br om o-4,4-d im eth yl-1-(4-n itr oben zen esu lfon yl)a ze-
1
tid in -2-on e, 4d . White solid. mp 80-85 °C. H NMR: δ 1.65
3-Br om o-3,4-d ip h en yloxeta n -2-on e, 2i. 1H NMR: δ 6.42
(s, 1H); 7.0-7.70 (m, 8H); 8.05 (dd, J ) 8 and 1 Hz, 2H). 13C
NMR: δ 51.10; 88.51; 128.76 (2C); 128.98 (2C); 129.08 (5C);
191.00. IR (neat): 1850 cm-1 (γ CO). Anal. Calcd for C15H11O2-
Br: C, 59.43; H, 3.66. Found: C, 59.56; H, 3.82.
(s, 3H); 1.80 (s, 3H); 4.70 (s, 1H); 8.12 (d, J ) 10 Hz, 2H); 8.45
(d, J ) 10 Hz, 2H). 13C NMR: δ 24.50; 25.65; 54.54; 69.52;
125.76 (2C); 129.77 (2C); 145.40; 152.13; 161.47. IR (neat):
1820 cm-1 (γ CO). Anal. Calcd for C11H11BrN2O5S: C, 36.38;
H, 3.05; N, 7.71. Found: C, 36.29; H, 2.93; N, 7.84.
Rep r esen ta tive P r oced u r e for th e P r ep a r a tion of
Su lfon a m id es. A suspension of lithium toluenesulfonamide
was prepared by dropwise addition of n-BuLi (1.25 M in
hexane, 40 mL, 0.05 mol) to a solution of p-toluenesulfonamide
(8.561 g, 0.05 mol) in THF (150 mL) at -78 °C. The cold bath
was removed, and the heavy white suspension was allowed to
warm to room temperature. After recooling to -78 °C, the
suspension was transferred by cannulation to a solution of
crotonyl chloride (0.025 mol, 2.6 g) in THF (10 mL) over a
period of 20 min. The reaction mixture was left stirring for 24
h. Water (40 mL) was carefully added, and the THF was
removed on the rotavap. The crude mixture was basified with
25% NaOH and extracted with ether (3 × 30 mL). The aqeous
phase was acidified (pH 2) with aqueous HCl and extracted
with ether (3 × 30 mL). The combined organic layers were
dried over MgSO4, and the ether was removed. The residue
was dissolved in a minimum of ether, and after 48 h, the
desired product crystallized out of the solution to give N-(but-
2-enoyl)-4-methylbenzenesulfonamide, 3a 26 (23%). White solid.
mp 126-128 °C. 1H NMR: δ 1.85 (dd, J ) 7.5 and 1.0 Hz,
3H); 2.45 (s, 3H); 5.82 (d, J ) 15.0 and 1.0 Hz, 1H); 6.85 (d, J
) 15.0 and 1.0 Hz, 1H); 7.35 and 7.95 (d, J ) 9.0 Hz, 4H);
8.95 (s, 1H). Anal. Calcd for C11H13NO3S: C, 55.21; H, 5.48;
N, 5.85. Found: C, 55.06; H, 5.46; N, 5.75.
3-Br om o-1-(4-n itr oben zen esu lfon yl)-4-p h en yla zetid in -
2-on e, 4e. White solid. mp 118-122 °C. H NMR: δ 4.70 (d,
1
J ) 3.75 Hz, 1H); 5.15 (d, J ) 3.75 Hz, 1H); 7.15-7.50 (m,
5H); 7.90 (d, J ) 12.5 Hz, 2H); 8.30 (d, J ) 12.5 Hz, 2H). 48.23;
67.80; 126.50 (2C); 127.55 (2C); 129.03 (2C); 129.91 (2C);
133.92; 134.60; 145.79; 152.13; 160.29. IR (neat): 1820 cm-1
(γ CO). Anal. Calcd for C15H10BrN2O5S: C, 43.92; H, 2.46; N,
6.83. Found: C, 44.12; H, 2.55; N, 6.94.
Gen er a l P r oced u r e for th e Rea ction of Allylic Alco-
h ols. To bis(collidine)bromine(I) hexafluorophosphate (0.71 g,
1.5 mmol) in methylene chloride (30 mL) was added a solution
of allylic alcohol (1.2 mmol) and collidine (0.15 g, 1.2 mmol) in
methylene chloride (10 mL) over 6 h. Subsequently, silica gel
(2 g) was added and the solvent was removed. The product
was purified by flash chromatography over silica gel. The
different results are reported Table 3.
3,3a -Dibr om oh exa h yd r oben zofu r a n , 6a . 1H NMR:
δ
1.40-2.10 (m, 8H); 3.95 (t, J ) 8.0 Hz, 1H); 4.08 (bs, 1H); 4.30
(t, J ) 8.0 Hz, 1H); 4.65 (t, J ) 8.0 Hz, 1H). 13C NMR: δ 19.15;
21.42; 24.65; 33.53; 57.72; 63.64; 71.40. Anal. Calcd for C8H12
-
Br2O: C, 33.84; H, 4.26. Found: C, 33.72; H, 4.51.
1
3-Br om o-2-p h en yloxeta n e, 6b. H NMR: δ 4.68 (q, J )
6 Hz, 1H); 4.95 (t, J ) 6 Hz, 1H); 5.01(t, J ) 6.0 Hz, 1H); 5.90
(d, J ) 6 Hz, 1H); 7.30-7.60 (m, 5H). 13C NMR: δ 43.19; 76.22;
91.99; 125.21 (2C); 128.66 (2C); 128.86; 139.40. Anal. Calcd
for C9H9BrO: C, 50.73; H, 4.26. Found: C, 50.82; H, 4.42.
N -(3-Me t h ylb u t -2-e n oyl)-4-m e t h ylb e n ze n e su lfon a -
1
m id e, 3b. White solid. H NMR: δ 1.93 (s, 3H); 2.20 (s, 3H);
2.45 (s, 3H); 4.90 (bs, 1H); 5.73 (s, 1H); 7.30 (d, J ) 11.7 Hz,
2H); 7.80 (d, J ) 11.7, 2H). Anal. Calcd for C12H15NO3S: C,
56.90; H, 5.97; N, 5.53. Found: C, 56.82; H, 5.85; N, 5.45.
4-Met h yl-N-(3-p h en yla cr yloyl)b en zen esu lfon a m id e,
3c.27 White solid. mp 137-138 °C. 1H NMR: δ 2.45 (s, 3H);
6.42 (d, J ) 18.7 Hz, 1H); 7.30-7.50 (m, 7H); 7.70 (d, J ) 18.7
Hz, 1H); 8.05 (d, J ) 12.5 Hz, 2H); 8.60 (s, 1H).
3-Br om o-2-m eth yl-4-p h en yloxeta n e, 6d . 1H NMR:
δ
1.85 (s, 3H); 4.75 (m, 1H); 4.85-4.95 (m, 2H); 7.30-7.50 (m,
5H). 13C NMR: δ 26.93; 48.83; 73.98; 90.35; 123.07; 126.27;
127.48; 128.46; 128.63; 128.75. Anal. Calcd for C10H11BrO: C,
52.89; H, 4.88. Found: C, 52.78; H, 4.68.
3-Br om o-2-(4-br om op h en yl)oxeta n e, 6e. 1H NMR:
δ
4.65 (q, J ) 6 Hz, 1H); 4.96 (qui, J ) 6 Hz, 2H); 5.85 (d, J )
6 Hz, 1H); 7.34 (d, J ) 8 Hz, 2H); 7.55 (d, J ) 8 Hz, 2H). 13C
NMR: δ 42.86; 76.24; 91.23; 122.8; 126.80 (2C); 131.80 (2C);
138.4. Anal. Calcd for C9H8Br2O: C, 37.02; H, 2.76. Found:
C, 37.42; H, 2.11.
4-N it r o -N -(3-Me t h y lb u t -2-e n o y l)b e n ze n e s u lfo n a -
1
m id e, 3d . White solid. H NMR: δ 1.85 (s, 3H); 2.10 (s, 3H);
5.15 (bs, 1H); 5.55 (s, 1H); 8.15 (d, J ) 9.0 Hz, 2H); 8.35 (d, J
) 9.0 Hz, 2H). Anal. Calcd for C11H12NO5S: C, 46.47; H, 4.25.
Found: C, 46.52; H, 4.28.
3-Br om o-2,2-d im eth yl-4-p h en yloxeta n e, 6f. 1H NMR: δ
1.56 (s, 3H); 1.69 (s, 3H); 4.40 (d, J ) 8 Hz, 1H); 5.60 (d, J )
8 Hz, 1H); 7.40-7.50 (m, 5H). 13C NMR: δ 25.09; 29.00; 54.07;
84.37; 84.88; 125.24 (2C); 128.51 (2C); 128.57; 139.66. Anal.
Calcd for C11H13BrO: C, 54.79; H, 5.43. Found: C, 54.85; H,
5.61.
4-Nitr o-N-(3-p h en yla cr yloyl)ben zen esu lfon a m id e, 3e.
1
White solid. mp 130-134 °C. H NMR: δ 5.10 (bs, 1H); 6.40
(d, J ) 15 Hz, 1H); 7.30-7.50 and 8.25-8.40 (m, 9H); 7.70 (d,
J ) 15 Hz, 1H). Anal. Calcd for C15H12NO5S: C, 54.21; H, 3.64.
Found: C, 54.14; H, 3.74.
Gen er a l P r oced u r e for th e P r ep a r a tion of Azetid in -
2-on es. To bis(collidine)bromine(I) hexafluorophosphate (0.75
g, 1.6 mmol) in methylene chloride (30 mL) was added a
solution of the sulfonamide 3 (1.2 mmol) in methylene chloride
(15 mL) by a push syringe over a period of 10 h. Subsequently,
silica gel was added to the reaction mixture and the solvent
J O9810361
(26) Niestroj, M.; Neumann, W. P.; Olaf, T. Chem. Ber. 1994, 127,
1131.
(27) Merck and Co, Inc. Br. Patent 902,881. Chem. Abstr. 1963, 58,
1410c.