The synthesis of fluorinated α-pyrans via fluorinated vinylcopper reagents

Article abstract of DOI:10.1016/j.jfluchem.2009.05.007

Fluorinated vinylcopper reagents were prepared in situ via reaction of fluorinated vinylbromides or iodides with cadmium or zinc powder followed by metathesis with Cu(I)Br. Hexafluoro-2-butyne was then added to the solution of the F-vinylcopper reagent wh

Full text of DOI:10.1016/j.jfluchem.2009.05.007

Journal of Fluorine Chemistry 130 (2009) 775–779
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
The synthesis of fluorinated
a-pyrans via fluorinated vinylcopper reagents
*
Donald J. Burton , Steven W. Hansen
Department of Chemistry, University of Iowa, Iowa City, IA 52242, United States
A R T I C L E I N F O
A B S T R A C T
Article history:
Fluorinated vinylcopper reagents were prepared in situ via reaction of fluorinated vinylbromides or
iodides with cadmium or zinc powder followed by metathesis with Cu(I)Br. Hexafluoro-2-butyne was
then added to the solution of the F-vinylcopper reagent which resulted in a stereospecific syn addition of
the F-vinylcopper reagent to the alkyne to provide in situ the corresponding dienylcopper reagent.
Subsequent acylation of the dienylcopper reagent gave a dienylketone, which spontaneously cyclized to
the 2H-pyran. This methodology provides a useful one flask route to fluorinated 2H-pyrans.
ß 2009 Elsevier B.V. All rights reserved.
Received 14 March 2009
Received in revised form 27 April 2009
Accepted 7 May 2009
Available online 18 May 2009
Keywords:
F-vinylcopper reagents
F-dienylcopper reagents
Fluorinated
a-pyrans
Stereospecific addition
Acylation
1. Introduction
and Cu(I)I (2E)-2,3-difluoro-3-iodoacrylic acid reacted with 1-
alkynes such as phenylacetylene, to form 3,4-difluoro-6-phenyl-
Organofluorine compounds have attracted the interest of
pharmaceutical and agrochemists, since replacement of hydrogen
atoms by fluorine atoms or fluoroalkyl groups can lead to major
changes in lipophilicity and polarity factors which often leads to
enhanced biological activity [1–5]. Pyrone derivatives are found in
many natural products that display important biological activities.
However, there has been little information reported on the
fluorinated analogs of these interesting heterocycles. England
and co-workers reported the seminal synthetic route to fluorine-
containing 2-pyrones via the Diels–Alder reaction of perfluoroa-
cryloyl fluorides with monosubstituted acetylenes, followed by
isomerization of the adducts and hydrolysis in aqueous sodium
bicarbonate [6] as illustrated in Eq. (1). Unfortunately, most of the
fluorinated 2-pyrone
2H-pyran-2-one, as illustrated in Eq. (2). A variety of alkynes were
employed under similar conditions, such as aryl, alkyl, and pyridyl
alkynes, and provided good to excellent isolated yields
(2)
(43–71%). Non-fluorine-containing cis-
vided -(Z)-alkylidinebutenolides [8] under similar conditions Eq.
(3). Our work gave only the
b-haloacrylic acids, pro-
g
(3)
2-pyrones. As an extension of this work, we were able to prepare
3,4-difluoro-5-iodo-substituted-2-pyrones via Larock electrophilic
cyclization of fluorine-containing enynes [7], as illustrated in Eq.
(4). The iodo-substituted pyrones can
(1)
derivatives prepared by this methodology were obtained in poor
yields.
Recently, we reported a more efficient and general synthetic
route to this class of compounds utilizing the (2E)-2,3-difluoro-3-
iodoacrylic acid synthon [7]. Under the co-catalysis of PdCl2(PPh3)2
* Corresponding author.
(4)
E-mail address: donald-burton@uiowa.edu (D.J. Burton).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.05.007

776
D.J. Burton, S.W. Hansen / Journal of Fluorine Chemistry 130 (2009) 775–779
be further elaborated to provide more functionalized fluorinated
2-pyrones.
2. Results and discussion
In contrast to the limited work on fluorinated 2-pyrones, the
formationoffluorinated a-pyranshasbeenachievedviathereaction
of fluoroolefins with carbon nucleophiles derived from diethylma-
lonate, ethyl acetoacetate and acetylacetone [9–11]. Our recent
work with F-vinyl and F-aryl copper reagents demonstrated that
these reagents readily added to hexafluoro-2-butyne (via syn
addition) to stereospecifically provide F-dienylcopper or F-arylvi-
nylcopper reagents [12–14], as illustrated in [Eqs. (5) and (6)].
(5)
(6)
Scheme 1.
Subsequent heating of the dienylketone gave the corresponding
pyran, as well as both isomers of the dienylketone Eq. (9). These
results are summarized in Table 2.The reaction of CF3CBB CCO2CH3
with (Z)-CF3CF CFCu was attempted. However, 19F NMR indicated
that the reaction was not regiospecific, and this reaction was not
investigated further.
In a previous report, we demonstrated that F-vinylcopper
reagents are easily acylated to provide the corresponding
unsaturated ketones [15]. Consequently, acylation of the dienyl-
copper reagents, 1, should provide the corresponding dienylk-
etone. If the carbonyl oxygen is sufficiently nucleophilic to attack
the vinyl carbon of the dienone, cyclization would yield the
corresponding 2H-pyran derivative. Scheme 1 illustrates the
overall concept. This approach would yield a one flask preparation
of the 2H-pyrans, since all the reagents are added sequentially.
Thus, when 1 was reacted with acyl halides, the dienylketone was
formed, which spontaneously cyclized to the pyran derivative [16].
Table 1 summarizes the reactions studied via this overall process.
In some cases protonation of the dienylcopper reagent occurred
[17] to give the reduced diene. Authentic samples of these reduced
products were prepared for comparison [18,19] Eq. (7).
(9)
3. Experimental
3.1. General experimental procedures
The 19F NMR spectra were recorded on a JEOL FX90Q Spectro-
meter. Chemical shifts have been reported relative in ppm upfield
from CFCl3 and were generally determined in CDCl3 solvent. 19F
NMR yields were determined by integration relative to internal
benzotrifluoride. Routine 1H NMR spectra were determined on a
JEOL FX90Q Spectrometer. Chemical shifts are reported in ppm
downfield from internal TMS. Infrared absorbance spectra were
recorded on a Beckman Accu Lab 8 Spectrophotometer as liquid
films between sodium chloride plates. All IR values have been
reported in units of reciprocal centimeters. Low-resolution mass
spectra (LRMS) were obtained with a Hewlett-Packard 5985 GC/
MS system at 70 eV. DMF was distilled from P2O5 under partial
vacuum. GLPC analyses were carried out on a Hewlett-Packard
5840A instrument using OV-101, SE-30 or Carbowax columns.
(7)
Increased steric hinderance at the vinyl carbon attacked by the
carbonyl oxygen allowed us to observe (in solution) the dienylk-
etone intermediate. Thus, when (Z)-CF3CCl CFCu was added to
hexafluoro-2-butyne, followed by acylation with benzoyl chloride,
the dienylketone could be detected by 19F NMR analysis of the
reaction mixture Eq. (8).
3.2. General procedure for the preparation of fluorinated-2H-pyrans
A 250 ml three-necked flask was equipped with a condenser,
magnetic stirring bar, a septum port, a thermometer, and a glass
tee leading to a source of dry nitrogen. Activated cadmium or zinc
powder [20,21] and DMF were added to the flask. A portion (ꢀ1/4)
of the fluorinated vinyl halide was added via syringe to the mixture
and stirred until the reaction started, as evidenced by a sharp rise
in temperature in some cases, where there was a long induction
period, the reaction was initiated with a crystal of iodine or a small
amount (40–50
ml) of PhC(O)Cl. After initiation, the remainder of
the vinyl halide was gradually added so that the temperature was
maintained at ꢀ50 8C. After all the vinyl halide had been added, the
reaction mixture was allowed to cool to room temperature (ꢀ1 h),
(8)

D.J. Burton, S.W. Hansen / Journal of Fluorine Chemistry 130 (2009) 775–779
777
stirring was continued for 1–2 h to complete the reaction (19F NMR
analysis confirmed complete conversion). Excess butyne was
removed under vacuum (0.2 mm Hg), and the solution repressur-
ized to atmospheric pressure with dry N2. The acid chloride was
added via syringe, the mixture stirred overnight at RT, then
vacuum distilled to near dryness. The distillate was washed twice
with ꢀ5 volumes of water, the organic layer concentrated and
dried over MgSO4, gravity filtered, then fractionally distilled.
Table 1
2H-pyrans formed by the reaction of fluorinated dienylcopper reagents with acid
halides.
Dienylcopper
Acid halide
2H-pyrans
Yield%a
CF3 C(O)Cl
56
3.3. Preparation of 2,2,3-trifluoro-4,5,6-tris (trifluoromethyl)-2H-
pyran, 2
Following the general procedure, trifluorovinylcopper was
prepared from F2C CFBr (27.8 g, 173 mmol), Zn (11.30 g,
173 mmol) and Cu(I)Br (27.8 g, l94 mmol) in DMF (150 ml). Then
CF3 CF2CF2C(O)Cl
42
hexafluoro-2-butyne (21.8 g, 173 mmol) was added to provide the
5
dienylcopper reagent; 19F NMR (DMF):
d
À53.4 (qd, JFF = 12 Hz,
5
2
4JFF = 4 Hz), À58.2 (q, JFF = 12 Hz), À102.8 (dd, JFF = 73 Hz,
3JFF = 27 Hz), À115.8 (dd, JFF = 118 Hz, JFF = 73 Hz), À160.0
(partially overlapped dd, 3JFF = 118 Hz, 3JFF = 27 Hz). Then
CF3C(O)Cl (28 g, 212 mmol) was added to the dienylcopper reagent
via the cold finger condenser. Work-up gave 32.7 g (56% based on
3
2
CH3 C(O)Cl
60
76
44
CF2 CFBr) of 2, bp 97–97.5 8C (750 mm Hg), GLPC purity = 96%. 19
F
5
5
NMR:
d
À55.4 (qq, JFF = 12.1 Hz, JFF = 12.1 Hz), À58.2 (dqm,
PhC(O)Cl
5
5
4JFF = 24.2 Hz, JFF = 12.1 Hz), À66.9 (q, JFF = 12.1 Hz), À69.5 (brd,
3JFF = 15.1 Hz), À119.5 (qtm, JFF = 24.2 Hz, JFF = 15.1 Hz). GCMS:
m/z (relative intensity): 340 (5.0, M+), 321 (100, M-F). IR: 1625 (s),
1419 (s), 1358 (s), 1332 (s), 1215 (vs), 1121 (s).
4
3
CH3C(O)Cl
3.4. Preparation of 2,2,3-trifluoro-4,5-bis(trifluoromethyl)-6-
heptafluorobutyl)-2H-pyran, 3
Following the general procedure, the trifluorovinylcopper
reagent was prepared from F2C CFBr (6.1 g, 38 mmol), Zn
(2.98 g, 45.6 mmol), and Cu(I)Br (6.96 g, 48.5 mmol) in DMF
(31 ml). Addition of CF3CBB CCF3 (8.5 g, 53 mmol) was followed by
addition of BF3ÁOEt2 (3.9 ml, 4.5 g, 31.7 mmol) (to convert any FÀ to
PhC(O)Cl
(50)
À
BF4 [22]). A portion of the dienylcopper reagent (28 ml) was
reacted with CF3CF2CF2C(O)Cl (2.8 ml, 4.34 g, 18.7 mmol). Work-
up gave, after two distillations, 3.5 g (42% based on CF3CF2CF2COCl)
a
Isolated yields; 19F NMR yield in parentheses.
of 3, bp 70–71 8C (67 mmHg). 19F NMR:
d
À54.1 (m), À58.2 (dqt,
5
5
3
4JFF = 23.8 Hz, JFF = 12 Hz, JFF = 1 Hz), À72.7 (d, JFF = 14 Hz),
then pressure filtered under N2 through a fritted glass filter to
remove unreacted metal powder. Anhydrous Cu(I)Br was then
added to the stirred filtered solution via a glass side-arm tube.
Conversion of the vinylzinc or cadmium reagent to the vinylcopper
reagent was complete within ꢀ15 min as evidenced by 19F NMR.
The flask was fitted with a cold finger condenser cooled with a Dry
Ice/isopropanol slush. Hexafluoro-2-butyne was then added drop
wise via the cold finger condenser (maintaining the reaction
temperature at ꢀ40 8C). After completion of the butyne addition,
4
5
5
À81.4 (t, JFF = 9.8 Hz, –113.1 (qqm, JFF = 18 Hz, JFF = 12 Hz),
À118.6 (qt, 4JFF = 23.8 Hz, 3JFF = 14.0 Hz), À123.7 (qm,
6JFF = 8.7 Hz). GCMS, m/z (relative intensity): 440 (9.0, M+), 271
(93.2, M-CF2CF2CF3), 243 (100, M-COC3F7). A major by-product
(17% by GLPC) was assigned the structure, presumably formed by
hydrolysis of 3
Table 2
Thermal isomerization of
GCMS, m/z (relative intensity): 418 (6.6, M+), 271 (77.2, M-
COC2F5), 193 (100, C5F7).
3.5. Preparation of 2,2,3-trifluoro-4,5-bis(trifluoromethyl)-6-methyl-
2H-pyran, 4
.
Time at 100 8C (h)
8%
9%
7%
The dienylcopper reagent was prepared from F2C CFBr (11.5 g,
71.2 mmol), Zn (7.39 g, 113 mmol), Cu(I)Br (13.2 g, 91.8 mmol)
and CF3CBB CCF3 (11.9 g, 73.4 mmol) in DMF (75 ml) as described in
Section 3.2. Then BF3ÁOEt2 (8.1 g, 56.9 mmol) was added to the
dienylcopper solution, followed by CH3C(O)Cl (5.6 g, 71 mmol).
0
100
41
15
3
0
39
33
47
0
20
52
50
(Flash distilled)
1.8
4.0

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D.J. Burton, S.W. Hansen / Journal of Fluorine Chemistry 130 (2009) 775–779
4
The reaction mixture was stirred for 1.5 h at RT, then flash distilled;
the distillate washed with cold water, extracted with 1.5 ml CH2Cl2
and the organic layer dried over MgSO4. Fractional distillation gave
À87.4 (q, JFF = 24 Hz). GCMS, m/z (relative intensity): 416 (0.7,
37ClM+), 414 (2.2, 35ClM+), 379 (38.3, M-Cl), 105 (100, PhCO+). The
reaction mixture was flash distilled under vacuum into a liquid
nitrogen cooled receiver. Analysis of the flash distillate by GCMS and
19F NMR spectroscopy indicated twonewcompounds (in addition to
(8). 19F NMR and GCMS were consistent with the formation of
12.1 g (60%, based on F2C CFBr) of 4, bp 59 8C/62 mmHg, GLPC
5
purity = 97% [23]. 19F NMR:
d
À55.2 (q, JFF = 13.4 Hz), À58.7 (dq,
5
3
4JFF = 28.2 Hz, JFF = 13.4 Hz), À66.6 (d, JFF = 16.4 Hz), À130.3 (m,
3
5
4JFF = 28.2 Hz, JFF = 16.4 Hz). 1H NMR:
d 2.32 (qq, JFH = 2.6 Hz,
6JFH = 1.1 Hz). GCMS, m/z (relative intensity): 286 (39.3, M+), 267
(44.4, M-F), 236 (100, M-CF2), 217 (26.6, M-CF3).
3.6. Preparation of 2,2,3-trifluoro-4,5-bis(trifluoromethyl)-6-phenyl-
2H-pyran, 5
The dienylcopper reagents was prepared from F2C CFBr
(11.5 g, 71.2 mmol), Zn (9.11 g, 139 mmol), Cu(I)Br (10.90 g,
76.0 mmol), and CF3CBB CCF3 (12.1 g, 75.2 mmol) in DMF (65 ml)
as described in Section 3.2. Then, BF3ꢁOEt2 (8.1 g, 56.9 mmol) was
added to the dienylcopper reagent, followed by PhC(O)Cl (10.5 g,
74.9 mmol). The reaction mixture was stirred overnight at RT, then
flash distilled; the distillate was washed with 200 ml cold water,
extracted with 1.5 ml CH2Cl2, the lower layer separated and dried
over MgSO4. Fractional distillation gave 18.0 g (76%) based on
F2C CFBr, of 5, bp 70–73 8C/1 mm Hg; GLPC purity = 99%. 19F
and
19F NMR of (9):
d
À59.6 (CF3,s), À59.8 (CF3, s), À63.2 (d, 4JFF = 25 Hz),
4
NMR:
d
À51.4 (q, 5JFF = 12 Hz), À57.5 (dq, 4JFF = 23 Hz, 5JFF = 12 Hz),
À87.5 (bd, q, JFF = 25 Hz. GCMS, m/z (relative intensity): 416 (0.6,
37ClM+), 414 (1.7, 35ClM+), 379 (11.5 M-Cl), 105 (100, PhCO+), 77
À65.8 (d, 2JFF = 15 Hz), À129.4 (m). GCMS, m/z (relative intensity):
(43.3, Ph+). 19F NMR of (7):
d
À51.5 (q, JFF = 12 Hz),À57.2 (dq,
5
348 (100, M+), 298 (92.5, M-CF2), 105 (29.2, Ph(O+), 77 (36.8 (Ph+).
4JFF = 23 Hz, JFF = 12 Hz), À75.6 (d, JFF = 15 Hz), À122.4 (qq,
5
4
4JFF = 23 Hz, JFF = 15 Hz). GCMS, m/z (relative intensity): 416 (2.6,
4
3.7. Preparation of 2,3-difluoro-3,4,5-tris(trifluoromethyl)-6-methyl-
2H-pyran, 6
37ClM+), 414 (7.1, 35ClM+), 379 (100, M-Cl), 139 (58.0, C2F2C6H5), 105
(46.0, PhCO+), 77 (41.6, Ph+), 69 (32.0, CF3).
When an NMR tube containing an aliquot of the flash distillate
was heated in an oil bath at 100 8C the dienone 8 was converted
mainly to 9 and 10. These results are tabulated in Table 2.
Following the general procedure (Z)-CF3CF CFCu was prepared
from (Z)-CF3CF CFI (15.5 g, 60.0 mmol), Cd (8.32 g, 74 mmol) and
Cu(I)Br (11.85 g, 82.6 mmol) in DMF (60 ml) Then, CF3CBB CCF3
(12.9 g, 79.5 mmol) was added to provide the dienylcopper
reagent. Then, CH3C(O)Cl (4.71 g, 60 mmol) was added to the
reaction mixture via syringe. Work-up gave 8.9 g (44%, based on
3.9. Preparation of (E,Z)-CF3CF CFC(CF3) C(CF3)H, 10
(Z)-CF3CF CFI) of 6, bp 60–61 8C (47 mmHg). 19F NMR:
d
À55.0
The (E,E)-((CF3CF CFC(CF3) C(CF3)Cu was prepared from (Z)-
CF3CF CFI (6.45 g, 25.0 mmol), Cd (3.10 g, 27.6 mmol), Cu(I)Br
(4.02 g, 28.0 mmol), and CF3CBB CCF3 (6.0 g, 37 mmol) in DMF
(21 ml) via the procedure described in Section 3.2. Addition of
aqueous HCl (2.0 ml of 12 M HCl), with cooling, followed by flash
distillation under vacuum provided a distillate with two layers. The
distillate was washed with 2 Â 45 ml H2O to remove DMF. The
5
5
4
(brq. JFF = 13.1 Hz, JFH = 2.6 Hz), À58.2 (dqd, JFF = 26.3 Hz,
5JFF = 13.1 Hz, 5JFF = 3.9 Hz), À80.6 (dd, 4JFF = 13.6 Hz, 3JFF = 5.8 Hz),
À109.6 (dqm, 3JFF = 11.3 Hz, 5JFF = 3.9 Hz), À125.5 (dqq,
4JFF = 26.3 Hz, JFF = 13.6 Hz, JFF = 11.3 Hz). 1H NMR:
d 2.33 (qq,
4
3
5JFH = 2.6 Hz, JFH = 1.1 Hz. GCMS, m/z (relative intensity): 336
(22.5, M+), 267 (100, M-CF3). (E,Z)-CF3CF CFC(CF3) C(CF3)H was
formed as a by-product (26% yield by 19F NMR integration (before
6
˚
product was dried over 4 A molecular sieves, then distilled to give
3.93 g (53%) of 10, bp 57–58 8C (GLPC purity = 97%). 19F NMR:
work-up); isolated yield 2.9 g (16%), bp 27 8C (46 mmHg). The 19
F
d
5
3
5
À59.9 (pentet m, JFF = 9.8 Hz, JFH = 7.7 Hz, JFF = 2.4 Hz), À60.8
(qdd, 5JFF = 9.8 Hz, 5JFF = 8.0 Hz, 4JFF = 7.0 Hz), À68.8 (dd,
4JFF = 21.7 Hz, 3JFF = 9.3 Hz), À141.3 (dqqqd, 3JFF = 130 Hz,
NMR was identical to an authentic sample of (E,Z)-
CF3CF CFC(CF3) C(CF3)H.
4
5
4
4JFF = 21.7 Hz, JFF = 7.0 Hz, JFF = 2.4 Hz, JFH = 2.4 Hz), À160.0
3.8. Preparation of 2-chloro-3-fluoro-4,5-bis(trifluoromethyl)-6-
(dqq, JFF = 130 Hz, JFF = 9.3 Hz, JFF = 8.0 Hz). 1H NMR:
(qm, JFH = 7.3 Hz). GCMS, m/z (relative intensity), 294 (37.4, M+),
d 6.49
3
3
5
phenyl-2H-pyran, 7
3
275 (72.1, M-F), 225 (92.4, M-CF3), 175 (100, M-CF2CF3).
Following the general procedure (Z)-CF3C(Cl) CFCu was
prepared from (Z)-CF3CCl CFI (1.10. g, 4.0 mmol), Cd (1.00 g,
8.9 mmol), Cu(I)Br (1.13 g, 7.9 mmol), CF3 CBB CCF3 (2.0 g, 12 mmol)
in 5.4 ml DMF. Then C6H5C(O)Cl (0.06 ml) was added to an aliquot
(0.5 ml) of the dienylcopper reagent in DMF (5.4 ml). 19F NMR
analysis of the reaction mixture was in agreement
3.10. Preparation of (Z)-F2C CFC(CF3) C(CF3)H, 11
The reagent, F2C CFZnBr, was prepared from F2C CFBr (5.7 g,
35.6 mmol) and Zn (2.0 g, 30.6 mmol) in DMF (12 ml) according to
the reported procedure [20]. Any unreacted F2C CFBr was
removed under vacuum. After repressurizing with N2, Cu(I)Br
(3.17 g, 22.1 mmol) was added to the zinc reagent mixture. Then,
CF3 CBB CCF3 (5.6 g, 34 mmol) was added drop wise via a cold finger
condenser (Dry Ice/isopropyl alcohol slush). The reaction mixture
was stirred for 1 h at 30 8C; then excess alkyne removed under
vacuum. After repressurization with N2, the reaction mixture was
cooled in an ice bath and 12 M HCl (1.5 ml) and H2O (1.0 ml) were
added and stirring continued for 20 min, at 10 8C, The product was
with the formation of the dienone (8), formed in 81% 19F NMR yield
(by integration vs. C6H5CF3). 19F NMR of (8):
d
À58.1 (q,
5
4
5JFF = 11 Hz),À58.6 (CF3, q, JFF = 11 Hz), À63.6 (d, JFF = 24 Hz),

D.J. Burton, S.W. Hansen / Journal of Fluorine Chemistry 130 (2009) 775–779
779
[2] J.T. Welch, S. Eswarakrishnan (Eds.), Fluorine in Bioorganic Chemistry, John Wiley
& Sons, New York, 1991.
[3] J.T. Welch, Tetrahedron 43 (1987) 3123–3197.
removed under vacuum; the distillate washed with H2O to remove
any DMF, and the clear, colorless lower layer analyzed by GLPC,
purity = 97%, yield 3.13 g (72% based on F2C CFZnX) of 11, bp 47–
[4] T. Hiyama (Ed.), Organofluorine Compounds; Chemistry and Application,
Springer, New York, 2000, pp. 137–182.
5
48 8C (746 mmHg). 19F NMR:
d
À58.4 (qdm, JFF = 11.4 Hz,
[5] R.E. Banks, B.E. Smart, J.C. Tatlow (Eds.), Organofluorine Chemistry, Principles and
Commercial Applications, Plenum, New York, 1994 (Chapter 3).
[6] D.C. England, E.A. Donald, F.J. Weigert, J. Org. Chem. 46 (1981) 144–147.
[7] Y. Wang, D.J. Burton, J. Org. Chem. 71 (2006) 3859–3862.
[8] M. Kotora, E. Negishi, Synthesis (1997) 121–128.
3JFH = 8.1 Hz),
À60.5
(dqd,
2
5JFF = 11.5 Hz,
5JFF = 11.4 Hz,
4JFF = 6.8 Hz), À93.3 (dd, JFF = 53.0 Hz, JFF = 34.2 Hz), À108.5
3
3
2
5
(ddq, JFF = 113.3 Hz, JFF = 53.0 Hz, JFF = 11.5 Hz), À173.3 (ddm,
3JFF = 113.3 Hz, JFF = 34.2 Hz); 1H NMR:
d 6.27 (q, JFH = 8.1 Hz).
3
3
[9] L.A. Rozov, N.S. Mirabekyants, Yu.V. Zeifman, Yu.A. Cheburkov, I.L. Knunyants, Izv.
Akad. Nauk SSSR, Ser. Khim. (1974) 1355.
GCMS, m/z (relative intensity): 244 (28.7, M+), 225 (34.9, M-F), 175
[10] S. Bartlett, R.D. Chambers, J.R. Kirk, A.A. Lindley, J. Chem. Soc. Perkin Trans. 1
(1983) 1235–1237.
(100, M-CF3).
[11] R.D. Chambers, J.R. Kirk, J. Chem. Soc. Perkin Trans. 1 (1982) 1239–1242.
[12] M. Yamamoto, D.J. Burton, D.C. Swenson, J. Fluorine Chem. 72 (1995) 49–54.
[13] S.W. Hansen, Ph.D. Thesis, University of Iowa, 1984.
4. Conclusion
[14] K.J. MacNeil, D.J. Burton, J. Org. Chem. 58 (1993) 4411–4417.
[15] T.D. Spawn, D.J. Burton, Bull. Soc. Chim. Fr. (6) (1986) 876–880.
[16] Chambers, ref. 11, reported a reaction which could be interpreted via the same
mechanistic scheme.
[17] The source of proton for production of the reduced dienes is not entirely clear; it
could be carboxylic acid impurities in the acid chloride reagent–but distillation of
CH3COCl under anhydrous conditions from N,N-dimethylaniline did not elim-
inate reduced diene formation. It could also be due to HCl impurities in the acid
halide, or in the case of CH3COCl abstraction from the methyl group of the acid
halide.
F-vinylcopperreagentsstereospecificallyadd(inasynmanner)to
hexafluoro-2-butyne to provide an F-dienylcopper reagent. Sub-
sequent acylation of the dienylcopper reagent produced a dienylk-
etone, which spontaneously cyclized to the corresponding 2-H-
pyran. All reactions arecarried out in one flask and this methodology
provides a new useful route to polyfluorinated 2-H pyrans.
[18] The formation of isomerized reduced diene is most likely due to fluoride ion
isomerization of the reduced diene from the original dienyl copper reagent. We
Acknowledgements
have previously observed similar fluoride ion isomerization of
C(CF3) C(CF3)– olefinic site in related diene systems [19].
[19] K.J. MacNeil, D.J. Burton, J. Org. Chem. 60 (1995) 4085–4089.
[20] C.R. Davis, D.J. Burton, in: P. Knochel, P. Jones (Eds.), Organozinc Reagents. A
Practical Approach, Oxford University Press, 1999, pp. 57–76.
[21] S.W. Hansen, T.D. Spawn, D.J. Burton, J. Fluorine Chem. 35 (1987) 415–420.
[22] In the absence of BF3ꢁOEt2, the major product after the addition of CF3CF2CF2COCl,
was CF3CF2CF2COF, which was unreactive towards the copper reagent.
[23] 19F NMR analysis of the reaction mixture indicated 15–20% 11.
a cis–
We gratefully appreciate the support of the National Science
Foundation for this work.
References
[1] R. Filler, Y. Kobayashi (Eds.), Biochemical Aspects of Fluorine Chemistry, Elsevier
Biochemical Press and Kodansha Ltd., New York, 1982.