Reactions of 1,3-dibromo-1,1-difluoro compounds with 1,8-diazabicyclo[5.4.0]undec-7-ene

Article abstract of DOI:10.1021/jo960992k

Difluorodienes result from the double dehydrobromination of 4-aryl-1,3-dibromo-1,1-difluorobutanes with DBU. Attempted syntheses of analogous 4-alkyl or 4-alkoxy dienes yield monoelimination products under mild conditions and unexpected trifluoro compounds under more vigorous conditions. 4-Aryl-1,1-difluoro-1,3-butadienes react rapidly with 4-phenyl-1,2,4-triazoline-3,5-dione in Diels-Alder reactions, but these dienes are unreactive toward several other electron-deficient and electron-rich dienophiles.

Full text of DOI:10.1021/jo960992k

6252
J . Org. Chem. 1996, 61, 6252-6255
Rea ction s of 1,3-Dibr om o-1,1-d iflu or o Com p ou n d s w ith
1,8-Dia za bicyclo[5.4.0]u n d ec-7-en e
Seth Elsheimer,* Christopher J . Foti, and Michael D. Bartberger
Department of Chemistry, University of Central Florida, Orlando, Florida 32816
Received May 29, 1996X
Difluorodienes result from the double dehydrobromination of 4-aryl-1,3-dibromo-1,1-difluorobutanes
with DBU. Attempted syntheses of analogous 4-alkyl or 4-alkoxy dienes yield monoelimination
products under mild conditions and unexpected trifluoro compounds under more vigorous conditions.
4-Aryl-1,1-difluoro-1,3-butadienes react rapidly with 4-phenyl-1,2,4-triazoline-3,5-dione in Diels-
Alder reactions, but these dienes are unreactive toward several other electron-deficient and electron-
rich dienophiles.
Diels-Alder reactions are widely used for the synthesis
order to determine if conjugation with an alkenyl sub-
stituent would produce a similar result, we carried out
the reaction with DBU on 1h . After 15 min at room
temperature, triene 2h was observed along with the
monoelimination product 3h . Slightly more vigorous
conditions (30 min, 38 °C) gave 2h as the major product.
The dehydrobrominations of 1 to 3 with DBU were
highly stereoselective yielding only the E isomers with
no Z visible by NMR. This probably reflects a confor-
mational preference for anti-1, which provides maximum
separation for the bulky CHR1R2 and trihalomethyl
groups, over more congested alternatives such as gauche-
1.
of various six-membered rings,1 and although fluorinated
dienophiles and/or perfluorinated dienes have been used
in these cycloadditions, partially fluorinated dienes have
received little attention.2,3 As part of our interest in the
chemistry of 1,3-dibromo-1,1-difluoro compounds,4 we
sought a general procedure for the preparation of 1,1-
difluorodienes involving double dehydrobromination of
1. One would expect the product dienes to find utility
in [4 + 2] cycloadditions thus providing a source of
geminally-fluorinated six-membered rings.
The previous observation that compounds 1 react with
hydroxide to yield R,â-unsaturated carboxylates4c led us
to use the non-nucleophilic base 1,8-diazabicyclo[5.4.0]-
undec-7-ene (DBU).5 The room temperature results are
summarized in eq 1. When the forming diene bears an
The possibility that more vigorous conditions might
force a second elimination on compounds 3 led to the
treatment of compounds 1c-e with excess DBU at 60-
70 °C overnight. Under these conditions, the trifluoro-
methyl compounds 4c-e were the major organic products
obtained6 (eq 2). This unexpected observation is not
aryl substituent (2a and 2b), the anticipated double
dehydrobromination proceeds as expected. If, however,
the substituent is alkyl, cycloalkyl, or alkoxy, the reaction
stops at monoelimination to yield (E)-1,1-difluoro-1-
bromo-2-alkenes (3c-g).
without precedent7 and is likely the result of fluoride
Apparently conjugation with an aryl group lowers the
activation energy for formation of difluoro dienes 2. In
(6) Under similar conditions 1a was converted into (E)-4,4,4-
trifluoro-1-phenyl-1-butene which has been synthesized by a different
route (Burdon, J .; Coe, P. L.; Marsh, C. R.; Tatlow, J . C. J . Chem. Soc.,
Chem. Commun. 1967, 1259), but no spectral data were reported. [1H
NMR δ 7.35 (m, 5H), 6.61 (d, J ) 15.8 Hz, 1H), 6.11 (dt, J ) 15.8 Hz,
J ′ ) 7.2 Hz, 1H), 2.98 (qdd, J ) 10.6, Hz, J ′ ) 7.2 Hz, J ′′ ) 1.3 Hz,
2H); 13C NMR δ 137.2, 136.7, 129.2, 128.6, 127.0, 126.4 (q, J ) 284.1
Hz), 117 (q, J ) 3.6 Hz); IR 3000, 2975, 2925, 2850, 1487, 1450, 1425,
1375, 1250, 1050, 950, 912, 875, 812, 750, 687, 650, 612 cm-1.] The
atypical regiochemistry of this alkene presumably reflects the ther-
modynamic advantage of conjugation with the aromatic ring. The
isomerization of (E)-1,1,1-trifluoro-4-phenyl-2-butene to (E)-4,4,4-
trifluoro-1-phenyl-1-butene is estimated to be exothermic by 2.09 kcal/
mol (Benson, S. W. Thermochemical Kinetics, 2nd ed.; Wiley: New
York, 1976).
X Abstract published in Advance ACS Abstracts, August 15, 1996.
(1) (a) Wassermann, A. Diels-Alder Reactions; Elsevier: New York,
1965. (b) Carruthers, W. Cycloaddition Reactions in Organic Synthesis;
Pergamon: Oxford, 1990.
(2) (a) Dolbier, W. R. In Chemistry of Organic Fluorine Compounds
II; Hudlicky, M., Pavlath, A., Eds.; ACS Monograph 187; American
Chemical Society: Washington, DC, 1995; p 797. (b) Chambers, R. D.
Fluorine in Organic Chemistry; Wiley: New York, 1973. (c) Perry, D.
R. A. Fluorine Chem. Rev. 1967, 1, 253.
(3) Weigert, F. J . J . Org. Chem. 1977, 42, 3859.
(4) (a) Gonzalez, J .; Foti, M. J .; Elsheimer, S. Org. Syn. 1995, 72,
225 (preprinted by Org. Syn. for ACS Organic Division, 1993). (b)
Gonzalez, J .; Foti, C. J .; Elsheimer, S. J . Org. Chem. 1991, 56, 4322.
(c) Elsheimer, S.; Slattery, D. K.; Michael, M.; Weeks, J .; Topoleski,
K. J . Org. Chem. 1989, 54, 3992. (d) Elsheimer, S.; Michael, M.;
Landavazo, A.; Slattery, D. K.; Weeks, J . J . Org. Chem. 1988, 53, 6151.
(5) Oediger, H.; Mo¨ller, F; Eiter, K. Synthesis 1972, 591.
(7) (a) Leroy, J .; Molines, H.; Wakselman, C. J . Org. Chem. 1987,
52, 290. (b) Molines, H.; Wakselman, C. J . Fluorine Chem. 1984, 25,
447.
S0022-3263(96)00992-9 CCC: $12.00 © 1996 American Chemical Society

Reactions of 1,3-Dibromo-1,1-difluoro Compounds
J . Org. Chem., Vol. 61, No. 18, 1996 6253
4-(2,4-Dib r om o-4,4-d iflu or ob u t yl)-1,2-d im et h oxyb en -
zen e (1b). A mixture of tert-butyl alcohol (15 mL), ethanol-
amine (2.39 g, 39.1 mmol), CuCl (0.389 g, 3.93 mmol), 1,2-
dimethoxy-4-allylbenzene (14.0 g, 78.5 mmol), and dibromo-
difluoromethane (32.8 g, 156 mmol) was stirred and heated
at 85-90 °C in a 185-mL pressure tube for 48 h. The cooled
mixture was decanted, leaving behind a black resin which was
extracted with 20 mL of hexane. The hexane extract was
combined with the decanted reaction mixture, and the result-
ing solution was filtered through 50 cm3 of silica gel with 40
mL of hexane. The filtrate was condensed by rotary evapora-
tion, and unreacted olefin was removed by distillation at 0.25
Torr and 80-100 °C leaving 10.32 g of 1b as a red viscous
liquid residue (34%): 1H NMR δ 6.85-6.64 (m, 3H), 4.35
(quintet, J ) 6.6 Hz, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.15 (m,
attack on dienes 2c-e. Fluoride ion is generated by
partial alkaline hydrolysis (trace moisture and DBU) of
the intermediate dienes 2 by a pathway we reported
previously.4d Attempts to employ an added fluoride
source to make this a viable procedure for the preparation
of trifluoromethyl compounds 4 have met with some
success.8 Investigations continue toward that end.
Diene 2a was found to be unreactive toward several
electron-deficient dienophiles including maleic anhy-
dride,9 diethyl malonate,10 dimethyl acetylenedicarboxy-
late, dimethyl maleate, cis-1,2-bis(phenylsulfonyl)ethyl-
ene, and DDQ. Diene 2a was also inert toward electron-
rich dienophiles including butyl vinyl ether, vinyltri-
methylsilane, and 1,4-cyclohexadiene. These observa-
tions are perhaps surprising in that photoelectron spec-
troscopy and theoretical studies indicate that vinylic
fluorine substituents do not significantly alter the HOMO
or LUMO energies.11
1H), 3.11 (m, 1H), 2.95 (td, J ) 13.4 Hz, J ′ ) 6.6 Hz, 2H); 13
NMR δ 149.5, 148.8, 129.9, 122.0, 121.2 (t, J ) 308 Hz), 112.7,
111.6, 56.2, 56.1, 51.6 (t, J ) 21.6 Hz), 46.5, 44.8; IR 1181 cm-1
C
.
1,3-Dibr om o-4-bu toxy-1,1-d iflu or obu ta n e (1d ). A mix-
ture of tert-butyl alcohol (10 mL), ethanolamine (0.800 g, 13.1
mmol), CuCl (0.026 g, 0.26 mmol), 90% allyl butyl ether (3.00
g, 23.6 mmol), and dibromodifluoromethane (11.0 g, 52.4 mmol)
was heated for 48 h. Fractional distillation of the crude liquid
gave two fractions: (1) bp 50-60 °C (0.4 Torr), 1.10 g of
unreacted olefin with some 1d ; (2) bp 63-66 °C (0.3 Torr), 1.04
g (14%) of 1d . For 1d : 1H NMR δ 4.25 (quintet, 1H), 3.66 (m,
2H), 3.49 (t, 2H), 3.22 (m, 1H), 2.86 (m, 1H), 1.55 (quintet, J
) 7 Hz, 2H), 1.38 (sextet, J ) 7 Hz, 2H), 0.9 (t, J ) 7 Hz, 3H);
13C NMR δ 121.2 (t, J ) 308 Hz), 73.9, 71.5, 49.0 (t, J ) 22.0
Unique among the dienophiles examined was 4-phenyl-
1,2,4-triazoline-3,5-dione (5),12 which reacted quickly with
2a or 2b at room temperature to yield the cycloadducts
6a and 6b, respectively (eq 3). To support the hypothesis
Hz), 42.7 (t, unresolved), 31.8, 19.4, 14.1; IR 1190 cm-1
.
(1,3-Dibr om o-3,3-d iflu or op r op yl)cycloh exa n e (1e). A
mixture of tert-butyl alcohol (10 mL), ethanolamine (0.831 g,
13.6 mmol), CuCl (0.027 g, 0.273 mmol), vinylcyclohexane (3.00
g, 27.2 mmol), and dibromodifluoromethane (11.5 g, 54.8 mmol)
was heated for 18 h. Distillation of the crude liquid product
(67-69 °C, 0.3 Torr) gave 4.71 g (54%) of 1e: 1H NMR δ 4.18
(m, 1H), 2.98 (m, 2H), 1.9-1.6 (m, 5H), 1.6-1.5 (m, 1H), 1.45-
1.0 (m, 5H); 13C NMR δ 121.6 (t, J ) 308 Hz), 53.7, 50.6 (t, J
that 6 results from an electrocyclic process, we monitored
by H NMR the reaction of a mixture of (Z)- and (E)-2a
1
with incrementally-added 5. Since (Z)-2a cannot readily
adopt the s-cis conformation required for a concerted [4
+ 2] cycloaddition, its reaction with dienophiles should
be much slower than that of (E)-2a . As expected, at room
temperature in the presence of 5, (E)-2a disappears to
yield 6a while (Z)-2a persists.
) 21.3 Hz), 44.1, 31.3, 28.1, 26.3, 26.1, 25.9; IR 1196 cm-1
.
(1,3-Dibr om o-3,3-d iflu or op r op yl)cycloocta n e (1f).
A
mixture of tert-butyl alcohol (10 mL), ethanolamine (0.659 g,
10.8 mmol), CuCl (0.0215 g, 0.217 mmol), vinylcyclooctane
(3.00 g, 21.7 mmol), and dibromodifluoromethane (9.17 g, 43.7
mmol) was heated for 24 h. Distillation of the crude liquid
(bp 100-106 °C, 0.3 Torr) gave 3.78 g (50%) of 1f: 1H NMR δ
4.23 (td, J ) 6.2 Hz, J ′ ) 2.9 Hz, 1H), 2.95 (m, 2H), 1.85 (m,
1H), 1.75-1.15 (m, 14H); 13C NMR δ 121.5 (t, J ) 308.3 Hz),
56.2 (t, unresolved), 50.5 (t, J ) 21.2 Hz), 43.2, 33.0, 29.5, 26.8,
Exp er im en ta l Section
Gen er a l. Except where otherwise specified, reagents were
commercial samples obtained from Aldrich Chemical Co. and
used without purification. Analytical and preparative GC was
carried out on a 8 ft × 0.25 in. Cu column packed with 10%
SE 30 on Chromosorb WHP (He flow ) 60 mL/min). All NMR
spectra were run in CDCl3 on a Varian Gemini 200 spectrom-
eter operating at 200 MHz for 1H and 50 MHz for 13C. All
new compounds were found to be >95% pure by NMR.
Infrared spectra were run as capillary films of neat liquids or
KBr pellets unless otherwise noted. Melting points are
uncorrected.
1,3-Dibr om o-1,1-d iflu or o Com p ou n d s 1. Gen er a l P r o-
ced u r e. Dibromodifluoromethane was added to alkenes in the
presence of CuCl and ethanolamine in tert-butyl alcohol using
a modification of a literature method.4b,13 The preparation of
1b is representative.
26.2, 26.0; IR 1198 cm-1
.
1-(2,4-Dibr om o-4,4-d iflu or obu tyl)cycloh exa n ol (1g). A
mixture of tert-butyl alcohol (15 mL), ethanolamine (3.48 g,
57.0 mmol), CuCl (0.564 g, 5.70 mmol), 1-allylcyclohexanol
(16.0 g, 114 mmol), and dibromodifluoromethane (47.6 g, 227
mmol) was heated for 48 h. Fractional distillation of the crude
liquid gave two fractions: (1) bp 44-46 °C (0.6 Torr), 5.0 g of
unreacted 1-allylcyclohexanol; (2) bp 90-100 °C (0.3 Torr),
10.02 g (25%) of 1g: 1H NMR δ 4.42 (quintet, J ) 6.4, 1H),
3.31 (m, 1H), 2.96 (m, 1H), 2.15 (m, 2H), 1.85 (br s, 1H), 1.7-
1.1 (m, 10H); 13C NMR δ 121.3 (t, J ) 308.3 Hz), 72.1, 53.6 (t,
J ) 21.0 Hz), 50.4, 41.6, 38.7, 37.2, 25.7, 22.2, 22.1; IR 1187
cm-1
.
1-(2,4-Dib r om o-4,4-d iflu or ob u t yl)cycloh exen e (1h ).
Phosphorus oxychloride (2.63, 17.2 mmol), contained in a 25-
mL addition funnel, was slowly added (caution!) to a stirring
mixture of 1g (3.00 g, 8.57 mmol) and pyridine (15 mL)
contained in a 50-mL, three-necked flask equipped with a
condenser. The mixture was warmed to 50 °C for 5 min, cooled
to room temperature, slowly poured over ice, and extracted
with diethyl ether (2 × 15 mL). The ether solution was washed
twice with 20-mL portions of 3 M HCl, once with water, and
then dried over anhydrous calcium chloride. All volatile
material was removed by rotary evaporation leaving 2.5 g
(88%) of red liquid 1h : 1H NMR δ 5.5 (m, 1H), 4.3 (m, 1H),
2.9 (m, 2H), 2.55 (d, J ) 7 Hz, 2H), 2.3-1.9 (m, 4H), 1.9-1.3
(m, 4H); 13C NMR δ 134.0, 126.8, 121.4 (t, J ) 308.1 Hz), 52.0
(8) Elsheimer, S.; Foti, C. J .; Foti, M. J . Unpublished results.
(9) The hydrocarbon analog of 2 reacts with maleic anhydride in
toluene at 100 °C in 5 h (Grummit, O.; Christoph, F. J . J . Am. Chem.
Soc. 1951, 73, 3479), but 2a did not react with maleic anhydride in
CDCl3 at 60 °C after 24 h.
(10) The roughly analogous 1,1-dimethoxy-1,3-butadiene yields a
cycloadduct with diethyl malonate in CCl4 at 25 °C in 1 h (van Balen,
H. C. J . G.; Broekhuis, A. A.; Scheeren, J . W.; Nivard, R. J . F. Recl.
Trav. Chim. 1979, 98, 36), but no reaction was observed for 2a with
diethyl malonate in CDCl3 after 2 days at 61 °C.
(11) Brundle, C. R.; Robin, M. B.; Kuebler, N. A.; Basch, H. J . Am.
Chem. Soc. 1972, 94, 1451.
(12) Cookson, R. C.; Gilani, S. S. H.; Stevens, I. D. R. Tetrahedron
Lett. 1962, 615.
(13) Burton, D. J .; Kehoe, L. J . J . Org. Chem. 1970, 45, 1339.
(t, J ) 21.4 Hz), 48.3, 43.8, 28.0, 25.9, 23.2, 22.4; IR 1202 cm-1
.

6254 J . Org. Chem., Vol. 61, No. 18, 1996
Elsheimer et al.
R ea ct ion s of 1 w it h DBU a t R oom Tem p er a t u r e.
Gen er a l p r oced u r e. A 3-fold excess of DBU was added to a
stirring ether solution of 1. The preparation of 2a is repre-
sentative.
7.3 Hz), 126.0 (t, J ) 23.3 Hz), 116.4 (t, J ) 301.9 Hz), 30.6,
30.2, 27.8, 27.0, 21.6, 13.1; IR 1660, 1225 cm-1
.
(E)-1-Br om o-4-bu toxy-1,1-diflu or o-2-bu ten e (3d). A mix-
ture of DBU (0.74 g, 4.9 mmol), 1d (0.50 g, 1.5 mmol), and
diethyl ether (10 mL) yielded 0.19 g (52%) of yellow liquid 3d :
1H NMR δ 6.35-5.98 (m, 2H), 4.15-3.95 (m, 2H), 3.43 (t, J )
7 Hz, 2H), 1.57 (m, 2H), 1.4 (m, 2H), 0.9 (t, J ) 7.3 Hz, 3H);
13C NMR δ 133.6 (t, J ) 7.0 Hz), 127.0 (t, J ) 24.1 Hz), 117.4
(t, J ) 301.5 Hz), 71.3, 68.5, 31.9, 19.5, 14.0; IR 1672, 1231
(4,4-Diflu or o-1,3-bu ta d ien yl)ben zen e (2a ). DBU (4.17
g, 27.4 mmol) was slowly added to a stirring solution of 1a 4c
(3.00 g, 9.15 mmol) in 15 mL of ether at a rate that maintained
the temperature below 30 °C. Solid DBU hydrobromide salt
formed during the addition. The resulting mixture was stirred
for an additional 15 min, diluted with 10 mL of ether, and
washed with two 20-mL portions of 3 M HCl to dissolve the
salt. The ether phase was separated and dried over anhydrous
calcium chloride. Rotary evaporation of the volatile material
left 0.84 g (55%) of pale yellow liquid 2a . The E/Z ratio was
determined by GC (column ) 150 °C) to be 9:1. The E and Z
isomers were separated by preparative GC. Note: the purified
dienes should be stored in solution in the dark below room
temperature to prevent polymerization. For (E)-2a : 1H NMR
and IR spectra were consistent with those previously reported:
cm-1
.
(E)-(3-Br om o-3,3-d iflu or op r op en yl)cycloh exa n e (3e).
DBU (1.43 g, 9.39 mmol) and 1e (1.00 g, 3.12 mmol) in 10 mL
of diethyl ether yielded 0.30 g (40%) of colorless liquid 3e: 1H
NMR δ 6.15 (ddt, J ) 15.7 Hz, J ′ ) 6.5 Hz, J ′′ ) 1.9 Hz, 1H),
5.75 (dtd, J ) 15.7 Hz, J ′ ) 9.8 Hz, J ′′ ) 1.3 Hz, 1H), 2.2-1.9
(m, 1H), 1.8-1.6 (m, 5H), 1.4-1.0 (m, 5H); 13C NMR δ 142 (t,
J ) 7.0 Hz), 125 (t, J ) 23.3 Hz), 118 (t, J ) 302 Hz), 39.6,
31.9, 26.1, 25.9; IR 1660, 1230 cm-1
.
(E)-(3-Br om o-3,3-d iflu or op r op en yl)cycloocta n e (3f). A
mixture of DBU (1.31 g, 8.60 mmol), 1f (1.00 g, 2.87 mmol),
and diethyl ether (10 mL) reacted to yield 0.30 g (39%) of
colorless liquid 3f: 1H NMR δ 6.15 (ddt, J ) 15.7 Hz, J ′ ) 6.5
Hz, J ′′ ) 1.9 Hz, 1H), 5.78 (dtd, J ) 15.6 Hz, J ′ ) 9.9 Hz, J ′′
) 1.3 Hz, 1H), 2.3 (unresolved m, 1H), 1.8-1.3 (m, 14H); 13C
NMR δ 143.5 (t, J ) 6.7 Hz), 124.7 (t, J ) 24.3 Hz), 118 (t, J
14
13C NMR δ 157.4 (dd, J ) 298.2 Hz, J ′ ) 292.5 Hz), 137.4,
131.6 (dd, J ) 11.7 Hz, J ′ ) 3.4 Hz), 129.2, 128.2, 126.7, 118.3
(dd, J ) 4.2 Hz, J ′ ) 2.2 Hz), 83.3 (dd, J ) 27.8 Hz, J ′ ) 17.0
Hz). For (Z)-2a : 1H NMR δ 7.27 (m, 5H), 6.44 (d, J ) 11.2
Hz, 1H), 6.14 (t, J ) 11.2 Hz, 1H), 5.46 (ddm, J ) 23.8 Hz, J ′
) 11.2 Hz, 1H); 13C NMR δ 158.5 (dd, J ) 298.9 Hz, J ′ ) 292.6
Hz), 137.3, 130.3 (dd, J ) 11.2 Hz, J ′ ) 7.6 Hz), 128.9, 128.5,
) 302 Hz), 39.8, 30.8, 27.4, 26.0, 25.0; IR 1660, 1231 cm-1
.
128.0, 119.1 (dd, unresolved), 79.7 (dd, J ) 27.8 Hz, J ′ ) 15.6
(E)-1-(4-Br om o-4,4-diflu or o-2-bu ten yl)cycloh exan ol (3g).
Reaction of DBU (1.91 g, 12.5 mmol), 1g (1.46 g, 4.17 mmol),
and diethyl ether (10 mL) yielded 0.75 g (67%) of yellow liquid
3g: 1H NMR δ 6.27 (dtt, J ) 15.5 Hz, J ′ ) 7.7 Hz, J ′′ ) 1.9
Hz, 1H), 5.88 (dtt, J ) 15.5 Hz, J ′ ) 9.8 Hz, J ′′ ) 1.3 Hz, 1H),
2.25 (dt, J ) 7.6 Hz, J ′ unresolved, 2H), 2.0-1.8 (br s, 1H),
1.7-1.0 (m, 10H); 13C NMR δ 133.2 (t, J ) 7.4 Hz), 129.9 (t, J
) 23.4 Hz), 117.2 (t, J ) 302.0 Hz), 71.8, 44.2, 37.6, 25.7, 22.2;
-1
Hz); IR (CHCl3) 1708 cm
.
1,2-Dim e t h oxy-4-(4,4-d iflu or o-1,3-b u t a d ie n yl)b e n -
zen e (2b). In a procedure similar to that used for the
preparation of 2a , a mixture of DBU (5.00 g, 32.8 mmol), 1b
(4.26 g, 11.0 mmol), and diethyl ether (14 mL) was stirred for
10 min at room temperature to yield 1.40 g (56%) of red liquid
which was mostly (E)-2b (<5% Z by 1H NMR). Note: to
prevent polymerization, 2b should be stored cold in solution.
IR 1660, 1225 cm-1
.
1
For (E)-2b: H NMR δ 6.95-6.75 (m, 3H), 6.51 (dd, J ) 15.9
Tr iflu or om eth yl Com p ou n d s 4. Gen er a l P r oced u r e.
These compounds are the unexpected products from the
reactions of the corresponding dibromides (1) with 3 equiv of
DBU in dioxane at 60-65 °C for 12-14 h. The preparation of
4c is representative.
Hz, J ′ ) 9.5 Hz, 1H), 6.38 (d, J ) 15.9 Hz, 1H), 5.10 (ddd, J )
24.1 Hz, J ′ ) 9.5 Hz, J ′′ ) 1.6 Hz), 3.90 (s, 3H), 3.86 (s, 3H);
13C NMR δ 157.2 (dd, J ) 297.6, J ′ ) 291.6 Hz), 149.6, 149.4,
131.3 (dd, J ) 11.6 Hz, J ′ ) 3.3 Hz), 130.5, 120.0, 116.4 (dd,
unresolved), 111.5, 108.7, 83.3 (dd, J ) 27.7, J ′ ) 17.0 Hz),
(E)-1,1,1-Tr iflu or o-2-n on en e (4c). DBU (2.83 g, 18.6
mmol) contained in a 25-mL addition funnel is slowly added
to a stirred mixture of 1c (2.0 g, 6.21 mmol) in 15-20 mL of
dioxane in a three-necked, round-bottomed flask connected to
a reflux condenser. During the slow addition of DBU at room
temperature, a precipitate of DBU hydrobromide salt is clearly
visible. After the addition of DBU was complete, the reaction
mixture was heated at 65 °C for 12 h. The dark brown reaction
mixture was cooled, diluted with 15 mL of diethyl ether, and
washed twice with 15-mL portions of 3 M HCl, at which point
the solids dissolved. The organic phase was separated, dried
over anhydrous calcium chloride, and then concentrated under
reduced pressure to yield 0.35 g of crude liquid 4c. GC and
1H NMR showed minor contamination by 3c and two other
56.2, 56.1; IR 1719 cm-1
.
Rea ction of 1h w ith DBU. P r ep a r a tion of (E)-1-(4,4-
Diflu or o-1,3-bu ta d ien yl)cycloh exen e (2h ) a n d (E)-1-(4-
Br om o-4,4-d iflu or o-2-bu ten yl)cycloh exen e (3h ). A mix-
ture of DBU (3.57 g, 23.4 mmol), 1h (2.50 g, 7.53 mmol), and
diethyl ether (15 mL) was reacted at room temperature for 10
min. Workup of a small sample of the reaction mixture showed
19% 2h , 55% 3h , and 26% unreacted 1h . Further reaction at
38 °C for 30 min gave 0.90 g of a yellow liquid that is 75% 2h
and 25% 3h . Pure samples of 2h and 3h were obtained by
preparatory GC (column ) 150 °C). For 2h : this unstable
compound decomposes rapidly unless stored cold in solution;
1H NMR δ 6.12 (d, J ) 15.8 Hz, 1H), 5.95 (dd, J ) 15.8 Hz, J ′
) 10.3 Hz, 1H), 5.73 (m, unresolved, 1H), 4.96 (ddd, J ) 24.5
Hz, J ′ ) 10.4 Hz, J ′′ ) 1.8 Hz, 1H), 2.2-2.0 (m, 4H), 1.85-1.5
(m, 4H); 13C NMR δ 156.9 (dd, J ) 297.0 Hz, J ′ ) 290.9 Hz),
136.0, 135.6 (dd, J ) 11.1 Hz, J ′ ) 3.3 Hz), 130.6, 114.3 (dd,
unresolved), 83.2 (dd, J ) 27.3 Hz, J ′ ) 17.3 Hz), 26.1, 24.5,
22.6, 22.5; IR 1696, 1613 cm-1. For 3h : 1H NMR δ 6.20 (dtt,
J ) 15.5 Hz, J ′ ) 6.8 Hz, J ′′ ) 1.9 Hz, 1H), 5.86 (dtt, J ) 15.5
Hz, J ′ ) 9.9 Hz, J ′′ ) 1.4 Hz, 1H), 5.6-5.4 (m, unresolved,
1H), 2.9-2.6 (m, 2H), 2.2-1.94 (m, 2H), 1.94-1.8 (m, 2H), 1.8-
1.4 (m, 4H); 13C NMR δ 136.0 (t, J ) 7.3 Hz), 134.5, 128.4 (t,
J ) 23.0 Hz), 124.3, 117.5 (t, J ) 301 Hz), 40.0, 28.3, 24.6,
1
minor products which were not characterized but had H NMR
signals consistent with (E)- and (Z)-2c A pure sample of 4c
was isolated by preparative GC (column T ) 150 °C): 1H NMR
δ 6.38 (dtq, J ) 15.8 Hz, J ′ ) 6.8 Hz, J ′′ ) 2.1 Hz, 1H), 5.61
(dqt, J ) 15.8 Hz, J ′ ) 6.4 Hz, J ′′ ) 1.6 Hz, 1H), 2.13 (m, 2H),
1.5-1.15 (m, 8H), 0.89 (t, 6.6 Hz, 3H); 13C NMR δ 141.3 (q, J
) 6.5 Hz), 123.6, (q, J ) 269.9 Hz), 118.6 (q, J ) 33.1 Hz),
31.7, 31.6, 28.8, 28.0, 22.7, 14.1; IR 1678, 1273, 1190, 1132
cm-1
.
(E)-4-Bu t oxy-1,1,1-t r iflu or o-2-b u t en e (4d ). A stirred
mixture of DBU (4.24 g, 27.9 mmol) and 1d (3.0 g, 9.3 mmol)
in 10 mL of dioxane was heated at 65 °C for 12 h. Workup
gave 0.49 g of crude product 4d . A pure sample of 4d was
isolated by preparative GC (column T ) 120 °C): 1H NMR δ
6.42 (dm, J ) 15.8 Hz, 1H), 5.92 (dqt, J ) 15.8 Hz, J ′ ) 6.5
Hz, J ′′ ) 1.9 Hz, 1H), 4.08 (m, 2H), 3.48 (t, J ) 6.6 Hz, 2H),
1.6 (m, 2H), 1.4 (m, 2H), 0.94 (t, J ) 7.3 Hz, 3H); 13C NMR δ
137.5 (q, J ) 6.3 Hz), 123.6, (q, J ) 269.7 Hz), 118.8 (q, J )
34.1 Hz), 71.3, 68.7, 31.9, 19.5, 14.0.
22.5, 22.1; IR 1737, 1666, 1231 cm-1
.
(E)-1-Br om o-1,1-d iflu or o-2-n on en e (3c). DBU (4.77 g,
31.3 mmol) and 1c4b (3.37 g, 10.5 mmol) in 20 mL of diethyl
ether yielded 1.37 g (54%) of colorless liquid 3c: 1H NMR δ
6.23 (dtt, J ) 15.5 Hz, J ′ ) 6.8 Hz, J ′′ ) 1.9 Hz, 1H), 5.86 (dtt,
J ) 15.5 Hz, J ′ ) 9.8 Hz, J ′′ ) 1.4 Hz, 1H), 2.1 (m, 2H), 1.5-
1.2 (m, 8H), 0.9 (t, J ) 6.5 Hz, 3H); 13C NMR δ 136.5 (t, J )
(E)-(3,3,3-Tr iflu or o-1-p r op en yl)cycloh exa n e (4e).
stirred mixture of DBU (4.29 g, 28.2 mol) and 1e (3.0 g, 9.4
mmol) in 10 mL of dioxane was heated at 60 °C for 14 h.
A
(14) (a) Burton, D. J .; Wheaton, G. A. J . Org. Chem. 1983, 48, 917.
(b) Hayashi, S.; Nakai, T.; Ishikawa, N.; Burton, D. J .; Naae, D. G.;
Kesling, H. S. Chem. Lett. 1979, 8, 983.

Reactions of 1,3-Dibromo-1,1-difluoro Compounds
J . Org. Chem., Vol. 61, No. 18, 1996 6255
Workup gave 0.50 g of crude liquid 4e. A pure sample of 4e
was isolated by preparative GC (column T ) 120 °C): 1H NMR
δ 6.33 (ddq, J ) 15.9 Hz, J ′ ) 6.5 Hz, J ′′ ) 1.9 Hz, 1H), 5.54
(dq, J ) 15.9 Hz, J ′ ) 6.3 Hz, 1H), 2.2-2.0 (m, 1H), 1.8-1.6
(m, 5H), 1.4-1.1 (m, 5H); 13C NMR δ 146.3 (q, J ) 6.2 Hz),
124.0, (q, J ) 269.8 Hz), 116.5 (q, J ) 33.4 Hz), 39.9, 31.9,
(ddm, J ) 10.2 Hz, J ′ ) 6.2 Hz, 1H), 5.67 (tm, J ) 4.8 Hz,
1H), 3.86 (s, 3H), 3.85 (s, 3H); 13C NMR δ 150.7, 150.5, 150.0
(d, J < 2 Hz), 149.7, 134.1 (dd, J ) 9.1 Hz, J ′ ) 6.7 Hz), 130.7,
129.7, 129.2, 126.0, 124.8, 121.8, 120.8 (dd, J ) 31.5 Hz, J ′ )
28.6 Hz), 114.4 (dd, J ) 264.6 Hz, J ′ ) 236.4 Hz), 112.1, 111.6,
56.7, 56.2. IR 1784, 1719, 1584, 1519, 1419, 1290, 1266, 1237,
1167, 1143, 1055, 1020 cm-1; HRMS calcd for C20H17N3O4F2
M+ ) 401.1188, found M+ ) 401.1161.
Rela tive Rea ctivity of (E)-2a ver su s (Z)-2a w ith Di-
en op h ile 5. A small sample of the 9:1 isomeric mixture of
2a was enriched in Z isomer by isolating some (Z)-2a from
another run and adding it to a sample of the original mixture.
The enriched mixture was dissolved in a small volume of
CDCl3 and the E/Z ratio was determined to be 1.7:1 by 1H
NMR integration of the C(2) hydrogens of the E and Z isomers
(δ 5.12 and 5.46, respectively). The NMR sample was sequen-
tially treated with four small aliquots of 5 in CDCl3 and
examined by 1H NMR after each addition. The relative areas
of peaks corresponding to each isomer of 2a revealed that the
Z isomer persisted while the E isomer progressively disap-
peared as 6a was formed.
26.0, 25.8; IR 1678, 1289, 1125 cm-1
.
Attem p ted Diels-Ald er Rea ction s of 2 w ith Va r iou s
Dien op h iles. Preliminary experiments were carried out with
excess dienophile in CDCl3 in sealed NMR tubes. The samples
1
were periodically examined by H NMR for disappearance of
starting material. If no apparent reaction was observed at
room temperature the sample was warmed to 60 °C and
reexamined after several hours.
Rea ction of 2a w ith 5. A solution of dichloromethane and
5 (1.05 g, 6.00 mmol) was slowly dripped into a stirring
solution of 2a (1.00 g, 6.02 mmol) in 15 mL of dichloromethane
at room temperature. The carmine color of 5 quickly disap-
peared as the reaction occurred. The solvent was removed
under vacuum yielding 2.10 g of crude solid, which was
purified by column chromatography (silica gel 230-400 mesh,
60 Å, 50:50 hexane:ethyl acetate). A white solid, 6a , was
obtained (1.30 g, 63%, mp ) 184-187 °C): 1H NMR δ 7.48-
7.28 (m, 10H), 6.47 (dd, J ) 10.3 Hz, J ′ ) 4.8 Hz, 1H), 6.22
Ack n ow led gm en t. We gratefully acknowledge the
donors of the Petroleum Research Fund, administered
by the American Chemical Society, for partial support
(21424-B1) and Research Corporation (C-2666) for
partial support.
(ddm, J ) 10.2, J ′ ) 5.9 Hz, 1H), 5.72 (t, J ) 4.8 Hz, 1H); 13
C
NMR δ 150.4, 150.0, 134.0, (dd, J ) 9.2 Hz, J ′ ) 6.9 Hz), 132.7,
130.7, 130.4, 129.7, 129.2, 127.4, 126.0, 120.8 (dd, J ) 31.5
Hz, J ′ ) 29.0 Hz), 120.6, 114.4 (dd, J ) 265.6 Hz, J ′ ) 238.6
Hz), 56.9; IR 1790, 1737, 1490, 1420, 1290, 1132, 1061 cm-1
;
HRMS calcd for C18H13F2N3O2 M+ ) 341.0977, found M+
341.0965 (intensity ) 78%), base peak ) 166 amu.
)
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 1b, 1d -h , (E)-2a , (Z)-2a , (E)-2b, 2h ,
3c-h , 4c-e, 6a , and 6b, and the 1H NMR study of the relative
reactivity of (E)- and (Z)-2a with 5 (44 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of this journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
Rea ction of 2b w ith 5. The procedure described above
for reaction of 2a with 5 was followed. A mixture of 5 (0.790
g, 4.51 mmol) and 2b (1.02 g, 4.51 mmol) in 15 mL of
dichloromethane was reacted at room temperature. Column
chromatography yielded 1.35 g (75%) of the white solid 6b (mp
) 130-134 °C): 1H NMR δ 7.5-7.3 (m, 5H), 6.97 (dd, J )
10.2 Hz, J ′ ) 2 Hz, 1H), 6.94 (d, J ) 2 Hz, 1H), 6.84 (d, J )
10.2 Hz, 1H), 6.48 (dd, J ) 10.2 Hz, J ′ ) 4.8 Hz, 1H), 6.21
J O960992K