A facile synthesis of 1,1-difluoroallenes from commercially available 1,1,1-trifluoro-2-iodoethane

Article abstract of DOI:10.1055/s-0030-1258438

1,1-Difluoroallenes are synthesized in good yield via zinc-promoted 1,2-elimination of 3,3-difluoro-2-iodoallylic acetates, which are prepared by the reaction of aldehydes or ketones with 1-iodo-2,2-difluorovinyllithium, generated from commercially available 1,1,1-trifluoro-2-iodoethane. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258438

PAPER
881
A Facile Synthesis of 1,1-Difluoroallenes from Commercially Available
1,1,1-Trifluoro-2-iodoethane
S
ynthesis of 1,1-D
e
ifluoroallen
n
es Oh, Kohei Fuchibe, Junji Ichikawa*
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tsukuba, 305-8571, Japan
Fax +81(29)8534237; E-mail: junji@chem.tsukuba.ac.jp
Received 30 November 2010; revised 19 January 2011
However, there are two factors that limit the scope of this
method: (a) the starting material, F2C=CBr2, is a high-
cost, potential ozone-depleting substance, and is now un-
available because of the ban on its industrial manufacture,
and (b) highly nucleophilic alkyllithiums are required in
the preparation of 1,1-difluoroallenes, which restricts the
choice of substrate. Here, we report an improved synthetic
method for 1,1-difluoroallenes to overcome these issues
using 1) an environmentally friendly and commercially
available compound as the starting material, and 2) an ef-
fective process for carrying out a 1,2-elimination reaction
under mild and tolerant reaction conditions.
Abstract: 1,1-Difluoroallenes are synthesized in good yield via
zinc-promoted 1,2-elimination of 3,3-difluoro-2-iodoallylic ace-
tates, which are prepared by the reaction of aldehydes or ketones
with 1-iodo-2,2-difluorovinyllithium, generated from commercially
available 1,1,1-trifluoro-2-iodoethane.
Key words: fluorinated allenes, metalation, carbanions, elimina-
tion, difluorovinylidenation
1,1-Difluoroallenes have attracted much attention be-
cause of their unusual reactivities, entailing them to be
used as synthetic building blocks for fluorinated mole-
cules. The Diels–Alder and [3+2]-cycloaddition reactions
of 1,1-difluoroallenes with 1,3-dienes and 1,3-dipoles
readily take place on the internal, nonfluorinated alkene
moiety to give the corresponding exo-difluoromethylene
First, we considered that the key intermediate, a 1-haloge-
nated 2,2-difluorovinyl anion 2 (Scheme 1), would be
generated by the addition of two equivalents of a strong
base to 1,1,1-trifluoro-2-haloethanes,7–9 which bear two
hydrogen atoms and are recognized to have much lower
ozone depletion potential (ODP). These compounds are
manufactured industrially for use as refrigerants or as
fluorinated intermediates. Second, we proposed a differ-
ent route to access the desired 1,1-difluoroallenes 1 from
3,3-difluoro-2-haloallylic acetates 3 (Scheme 1) on treat-
ment with a zerovalent metal instead of highly reactive
alkyllithiums, which would promote the 1,2-elimination
from acetates 3 to form one more double bond under mild
conditions. This sequence would expand the scope of the
substrates.
compounds.1
For
example,
1,1-difluoroallene
(F2C=C=CH2), with a low LUMO energy level, gives an
excellent yield (>99%) of the cyclized product with cyclo-
pentadiene under very mild conditions (–20 °C, 1 min),
while
the
nonfluorinated
counterpart
allene
(H2C=C=CH2) requires vigorous conditions (200–
230 °C) to give the product in a modest yield (49%).1a,f
The [2+2]-cycloaddition reactions with alkenes and
alkynes occur on the terminal, fluorinated alkene moiety
to give ring fluorinated cyclobutane2a and cyclobutene2b
derivatives. 1,1-Difluoroallenes also react with various
nucleophiles to afford CF2-terminal or internal addition
products selectively, depending on the character of the nu-
cleophile.3
R1
O
1)
R2
base (2 equiv)
– HF, – H+
X
Although the parent 1,1-difluoroallene has been known
since the 1950s,4 very few synthetic methods for the 3-
substituted 1,1-difluoroallenes have been reported.3a,5 Re-
cently, we have developed a versatile synthetic method
for 3-substituted 1,1-difluoroallenes 1 using two steps: (i)
lithiation of 1,1-dibromo-2,2-difluoroethene with butyl-
lithium generates 1-bromo-2,2-difluorovinyllithium
(F2C=CBrLi), which in turn, reacts with aldehydes or ke-
tones to form 2-bromo-3,3-difluoroallylic acetates, and
(ii) treatment of the bromoacetates with butyllithium
gives 1,1-difluoroallenes via the 1,2-elimination of lithi-
um acetate.6
CF3CH2X
CF2
–
2) acetylation
2
X
R1
M0
– M(OAc)X
F2C
AcO
R1
R2
F2C
R2
3
1
Scheme 1 A synthetic plan for 1,1-difluoroallenes from a 1,1,1-
trifluoro-2-haloethane
1,1,1-Trifluoro-2-iodoethane was selected as the starting
material because of its ease of handling (bp 55–56 °C/760
Torr). The lithiation of 1,1,1-trifluoro-2-iodoethane with
two equivalents of lithium diisopropylamide at low tem-
peratures (–93 to –85 °C) successfully gave 2,2-difluoro-
1-iodovinyllithium (2, Table 1).10 Lithium species 2 then
SYNTHESIS 2011, No. 6, pp 0881–0886
x
x
.
x
x
.2
0
1
1
Advanced online publication: 14.02.2011
DOI: 10.1055/s-0030-1258438; Art ID: F21510SS
© Georg Thieme Verlag Stuttgart · New York

882
K. Oh et al.
PAPER
reacted with one equivalent of either an aldehyde or a ke- butyllithium-promoted 1,2-elimination.6,11,12 The condi-
tone, and was subsequently acetylated with acetic anhy- tions of the zinc-promoted 1,2-elimination were opti-
dride (Table 1, entries 1–8) or with isopropenyl acetate mized, as shown in Table 2. In most cases, 1,1-
and p-toluenesulfonic acid (entry 9) to afford 3,3-difluo- difluoroallenes 1 were obtained in good yield on treatment
ro-2-iodoallylic acetates 3 in good yield.
of acetates 3 with two equivalents of zinc, either in N,N-
dimethylformamide or in tetrahydrofuran, at room tem-
perature for 3–12 hours (Table 2, entries 1–6). However,
1,1-difluoroallene 1g was only formed in N,N-dimethyl-
formamide, and not in tetrahydrofuran (Table 2, entries 7
Then, a facile and effective route by the zinc-promoted
1,2-elimination of acetates 3 under mild and tolerant reac-
tion conditions (e.g., at room temperature for several
hours) was found compared with the previously used n-
Table 1 Synthesis of 1,1-Difluoroallenes 1 via Difluorovinylidenation of Carbonyl Compounds
R1
1)
O
(1 equiv)
I
R2
THF, –93 to –30 °C, 2 h
I
R1
R2
F2C
R1
R2
LDA (2 equiv)
Zn (2 equiv)
CF3CH2I
F2C
F2C
THF
–93 to –85 °C
30 min
2) Ac2O (1.2 equiv)
–30 to 0 °C, 2 h
DMF or THF
r.t., 3–12 h
AcO
3a–i
Li
2
1a–i
Entry Carbonyl compound
3,3-Difluoro-2-iodoallylic acetate 3 Yield of 3 (%) 1,1-Difluoroallene 1
Yield of 1 (%) (time)
1a: 86 (3 h)
I
F2C
1
3a: 82
F2C
F2C
•
O
AcO
I
I
O
F2C
AcO
•
2
3b: 84
3c: 83
1b: 87 (6 h)
1c: 82 (6 h)
CH2(CH2)7Me
CH2(CH2)7Me
CH2(CH2)7Me
F2C
AcO
3
F2C
•
O
t-Bu
t-Bu
I
F2C
AcO
t-Bu
4
3d: 87
3e: 83
1d: 92 (6 h)
1e: 93 (12 h)
F2C
F2C
•
•
O
I
I
O
5
F2C
AcO
F2C
AcO
6
3f: 81
3g: 73
1f: 95 (6 h)
F2C
F2C
•
•
O
I
I
N
N
F2C
AcO
7
1g: 71 (12 h)
O
N
F2C
AcO
8
3h: 82
3i: 80a
1h: 74 (6 h)
1i: 86 (8 h)
F2C
F2C
•
•
O
CO2Me
CO2Me
MeO2C
I
F2C
AcO
9
O
a Acetylation was performed with isopropenyl acetate and TsOH.6
Synthesis 2011, No. 6, 881–886 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,1-Difluoroallenes
883
and 8), although the reason for this is not clear at present.13
3-Substituted 1,1-difluoroallenes with a primary alkyl
group were produced readily using this method, while the
yield decreased when the reaction period was extended by
several hours (Table 2, entries 1 and 2). In contrast, the
yield of 1,1-difluoroallenes with a secondary or tertiary
alkyl group at the 3-position remained steady, even after
an extended reaction time (Table 2, entries 3–5). This may
be the result of the stability of 1,1-difluoroallenes.
from Tosoh F-tech, Inc., and distilled from activated 4 Å molecular
sieves. This compound can also be purchased from Tokyo Chemical
Industry Co., Ltd. or Sigma-Aldrich Co. NMR and IR Spectra of
compounds 1a, 1c, 1d, and 1f are in agreement with the published
data.6
1,1-Difluoro-2-iodo-5-phenylpent-1-en-3-yl Acetate (3a); Typi-
cal Procedure
To a THF (10 mL) solution of (i-Pr)2NH (2.8 mL, 20 mmol) was
added BuLi (12.0 mL, 1.67 M in hexane, 20.0 mmol) over 10 min
at 0 °C under argon. The resulting solution was allowed to stir for
an additional 15 min, and then cooled to –93 °C using a cold hexane
bath. To this cold LDA solution was added a THF (5 mL) solution
of CF3CH2I (2.10 g, 10.0 mmol) over 10 min, keeping the tempera-
ture between –93 and –85 °C. After stirring for 20 min at the same
temperature, a THF (5 mL) solution of 3-phenylpropanal (1.34 g,
10.0 mmol) was added over 5 min, keeping the temperature be-
tween –93 and –85 °C. The mixture was stirred for an additional 30
min, then warmed to –30 °C over 90 min. After the addition of
Ac2O (1.23 g, 12.0 mmol), the mixture was allowed to warm to 0 °C
over 2 h. The reaction was quenched with sat. aq NH4Cl (20 mL),
and the product was extracted with Et2O (3 × 20 mL). The combined
organic layers were washed with brine (20 mL) and dried (Na2SO4).
After removal of the solvent under reduced pressure, the residue
was purified by column chromatography (hexane–EtOAc, 20:1).
The acetate 3a was obtained as a colorless liquid (3.01 g, 82%).
Table 2 Optimization of the Zinc-Promoted 1,2-Elimination
Entry Acetate 3 Zn (equiv) Solvent
Time (h) Yield of 1 (%)
1
2
3
4
5
6
7
8
3a
3a
3d
3d
3d
3d
3g
3g
2
2
2
2
2
2
2
4
DMF
DMF
DMF
DMF
DMF
THF
3
6
1a: 86
1a: 72a
1d: 83
1d: 92
1d: 90
1d: 88
1g: 71
1g: traceb
3
6
12
6
DMF
THF
8
IR (ATR): 3028, 2954, 1743, 1716, 1267, 1219, 1024, 698 cm–1.
12
1H NMR (500 MHz, CDCl3): d = 1.87–1.93 (m, 1 H), 2.05–2.17 (m,
1 H), 2.07 (s, 3 H), 2.58 (t, J = 7.2 Hz, 2 H), 4.98 (t, J = 7.2 Hz, 1
H), 7.17–7.22 (m, 3 H), 7.29 (dd, J = 7.3, 7.6 Hz, 2 H).
a Allene 1a partly decomposed to a complex mixture.
b Acetate 3g was recovered quantitatively.
13C NMR (126 MHz, CDCl3): d = 20.9, 30.9, 36.0, 53.8 (dd,
JC,F = 25, 26 Hz), 68.9 (d, JC,F = 3 Hz), 126.2, 128.2, 128.5, 140.2,
154.0 (dd, JC,F = 286, 286 Hz), 169.6.
19F NMR (470 MHz, CDCl3): d = 89.2 (d, JF,F = 22 Hz, 1 F), 90.2
(d, JF,F = 22 Hz, 1 F).
HRMS (ESI+): m/z calcd for C13H13F2IO2 + Na [M + Na]+:
388.9826; found: 388.9830.
Owing to the mild conditions of the zinc-promoted 1,2-
elimination, 1,1-difluoroallenes bearing a pyridine ring or
an ester functionality were synthesized in good yield
(Table 1, entries 7 and 8). A 3,3-disubstituted 1,1-difluo-
roallene was obtained in high yield from a 1,1-disubstitut-
ed 2-iodo-3,3-difluoroallylic acetate, which was prepared
from the corresponding ketone (Table 1, entry 9).
1,1-Difluoro-2-iodododec-1-en-3-yl Acetate (3b)
Prepared from 1,1,1-trifluoro-2-iodoethane (840 mg, 4.00 mmol);
yield: 84%; colorless liquid.
In summary, we have developed a general and efficient
method for the synthesis of 1,1-difluoroallenes from com-
mercially available and environmentally friendly 1,1,1-
trifluoro-2-iodoethane under mild reaction conditions.
This facile and low-cost synthesis allows 1,1-difluoroal-
lenes to be used as practical building blocks for the syn-
thesis of a various useful fluorinated molecules. Their
application is in progress in our laboratory and will be re-
ported in due course.
IR (ATR): 2925, 2856, 1749, 1716, 1458, 1371, 1269, 1225, 1024,
962, 604 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.88 (t, J = 6.9 Hz, 3 H), 1.19–1.35
(br, 14 H), 1.52–1.61 (m, 1 H), 1.65–1.74 (m, 1 H), 2.07 (s, 3 H),
4.94 (t, J = 7.2 Hz, 1 H).
13C NMR (126 MHz, CDCl3): d = 14.0, 20.9, 22.6, 24.5, 28.9, 29.2,
29.30, 29.34, 31.8, 34.2, 54.1 (dd, JC,F = 24, 26 Hz), 69.3 (d, JC,F = 3
Hz), 153.9 (dd, JC,F = 286, 299 Hz), 169.6.
19F NMR (470 MHz, CDCl3): d = 88.3 (d, JF,F = 24 Hz, 1 F), 89.6
(d, JF,F = 24 Hz, 1 F).
HRMS (EI): m/z calcd for C12H19F2I [M AcOH]+: 328.0500; found:
NMR spectra were recorded on a Bruker Avance 500 or a Bruker
Avance 400 spectrometer in CDCl3. Chemical shift values were
given in ppm relative to internal SiMe4 (for H NMR: d = 0.00),
1
CDCl3 (for 13C NMR: d = 77.0), and C6F6 (for 19F NMR: d = 0.0).
Mass spectra (EI-TOF or ESI-TOF) were recorded on Jeol JMS-
T100GCv or JMS-T100CS mass spectrometer. IR spectra were re-
corded by ATR (attenuated total reflectance) method on a Horiba
FT-720 spectrometer. Column chromatography and preparative
TLC were conducted on silica gel (Silica Gel 60 N, Kanto Chemical
Co., Inc. for column chromatography and Wakogel B-5F, Wako
Pure Chemical Industries for PTLC, respectively). All reactions
were conducted under argon. THF and DMF were dried by passing
over a column of activated alumina followed by a column of Q-5
scavenger (Engelhard). 1,1,1-Trifluoro-2-iodoethane was obtained
328.0478.
1,1-Difluoro-2-iodo-5-(1-naphthyl)pent-1-en-3-yl Acetate (3c)
Prepared from 1,1,1-trifluoro-2-iodoethane (840 mg, 4.00 mmol);
yield: 83%; pale yellow liquid.
IR (ATR): 3047, 2939, 1743, 1716, 1371, 1269, 1225, 1026, 966,
798 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.87–1.96 (m, 1 H), 1.97 (s, 3 H),
2.04–2.13 (m, 1 H), 2.92 (t, J = 8.1 Hz, 2 H), 5.00 (tdd, J = 6.4, 2.2,
1.4 Hz, 1 H), 7.19 (d, J = 6.9 Hz, 1 H), 7.28 (dd, J = 7.1, 7.1 Hz, 1
Synthesis 2011, No. 6, 881–886 © Thieme Stuttgart · New York

884
K. Oh et al.
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H), 7.39 (d, J = 8.0 Hz, 1 H), 7.41 (d, J = 7.0 Hz, 1 H), 7.61 (d,
J = 8.2 Hz, 1 H), 7.74 (d, J = 8.8 Hz, 1 H), 7.90 (d, J = 8.6 Hz, 1 H).
5.0 Hz, 1.8 H), 7.20 (dd, J = 7.5, 7.5 Hz, 1.2 H), 7.28 (t, J = 7.5 Hz,
2 H).
13C NMR (126 MHz, CDCl3): d = 20.9, 28.1, 35.4, 53.8 (t, JC,F = 25
Hz), 69.2 (d, JC,F = 3 Hz), 123.4, 125.5, 126.0 (2 C), 127.1, 128.9,
131.5, 133.9, 136.3, 154.1 (dd, JC,F = 299, 286 Hz), 169.6.
19F NMR (470 MHz, CDCl3): d = 89.4 (d, JF,F = 22 Hz, 1 F), 90.3
(d, JF,F = 22 Hz, 1 F).
HRMS (EI): m/z calcd for C17H15F2IO2 [M]+: 416.0085; found:
416.0059.
13C NMR (126 MHz, CDCl3): d = 20.8, 20.9, 21.7, 23.1, 35.8, 36.0,
42.3, 42.7, 54.0 (dd, JC,F = 25, 25 Hz), 54.2 (dd, JC,F = 26, 26 Hz),
68.0 (d, JC,F = 3 Hz), 126.5, 126.7, 126.8, 128.58, 128.61, 145.2,
145.5, 153.7 (d, JC,F = 299, 286 Hz), 153.9 (d, JC,F = 300, 286 Hz),
169.4, 169.5.
19F NMR (470 MHz, CDCl3): d = 88.8 (d, JF,F = 23 Hz, 0.4 F), 89.6
(d, JF,F = 21 Hz, 0.6 F), 89.7 (d, JF,F = 23 Hz, 0.4 F), 90.2 (d,
JF,F = 21 Hz, 0.6 F).
5-(4-tert-Butylphenyl)-1,1-difluoro-2-iodo-4-methylpent-1-en-
3-yl Acetate (3d)
HRMS (ESI+): m/z calcd for C14H15F2IO2 + Na [M + Na]+:
402.9982; found: 403.0000.
Prepared from 1,1,1-trifluoro-2-iodoethane (840 mg, 4.00 mmol);
yield: 87% (diastereomer ratio = 1:1); pale yellow liquid.
1,1-Difluoro-2-iodo-4-methyl-5-(3-pyridyl)pent-1-en-3-yl Ace-
tate (3g)
Prepared from 1,1,1-trifluoro-2-iodoethane (840 mg, 4.00 mmol);
IR (ATR): 2962, 2871, 1741, 1716, 1510, 1462, 1369, 1269, 1225,
1020, 968, 606, 573 cm–1.
yield: 73% (diastereomer ratio = 6:4); colorless liquid.
1H NMR (500 MHz, CDCl3): d = 0.74 (d, J = 6.4 Hz, 1.5 H), 0.91
(d, J = 6.2 Hz, 1.5 H), 1.15–1.45 (m, 1 H), 1.31 (s, 9 H), 2.06 (s, 1.5
H), 2.09 (s, 1.5 H), 2.05–2.13 (m, 0.5 H), 2.34 (dd, J = 13.5, 9.5 Hz,
0.5 H), 2.67 (d, J = 12.2 Hz, 0.5 H), 2.92 (d, J = 13.5 Hz, 0.5 H),
4.70 (d, J = 10.0 Hz, 0.5 H), 4.75 (d, J = 9.5 Hz, 0.5 H), 7.08 (d,
J = 8.4 Hz, 1 H), 7.09 (d, J = 8.3 Hz, 1 H), 7.30 (d, J = 8.4 Hz, 1 H),
7.31 (d, J = 8.3 Hz, 1 H).
13C NMR (126 MHz, CDCl3): d = 14.5, 14.8, 20.8, 31.4, 34.3, 37.6,
38.0, 38.4, 39.1, 53.3 (dd, JC,F = 26, 26 Hz), 73.3 (d, JC,F = 3 Hz),
73.4 (d, JC,F = 3 Hz), 125.2, 128.7, 128.8, 136.0, 136.4, 148.9,
149.0, 154.3 (dd, JC,F = 298, 286 Hz), 154.4 (dd, JC,F = 297, 286
Hz), 169.7, 169.8.
19F NMR (470 MHz, CDCl3): d = 88.5 (d, JF,F = 23 Hz, 0.5 F), 89.1
(d, JF,F = 22 Hz, 0.5 F), 89.8 (d, JF,F = 23 Hz, 0.5 F), 90.6 (d,
JF,F = 22 Hz, 0.5 F).
HRMS (ESI+): m/z calcd for C18H23F2IO2 + Na [M + Na]+:
459.0608; found: 459.0610.
IR (ATR): 2968, 2933, 1736, 1714, 1425, 1371, 1265, 1221, 1024,
968, 793, 715 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.75 (d, J = 7.0 Hz, 1.6 H), 0.92
(d, J = 6.0 Hz, 1.4 H), 2.10–2.11 (m, 4.4 H), 2.40 (dd, J = 13.5, 9.5
Hz, 0.6 H), 2.72 (d, J = 10.0 Hz, 0.4 H), 2.99 (dd, J = 13.5, 4.5 Hz,
0.6 H), 4.72 (d, J = 10.0 Hz, 0.6 H), 4.78 (d, J = 9.5 Hz, 0.4 H), 7.28
(dd, J = 8.0, 4.0 Hz, 1 H), 7.53 (d, J = 8.0 Hz, 1 H), 8.45 (s, 1 H),
8.49 (d, J = 4.5 Hz, 1 H).
13C NMR (126 MHz, CDCl3): d = 14.3, 14.6, 20.79, 20.83, 35.3,
35.6, 38.3, 39.0, 52.7 (dd, JC,F = 25, 25 Hz), 72.9 (d, JC,F = 3.5 Hz),
73.2 (d, JC,F = 3.2 Hz), 123.4, 134.8, 135.2, 136.8, 136.9, 147.3,
147.5, 150.0, 150.1, 154.4 (dd, JC,F = 299, 286 Hz), 154.5, (dd,
JC,F = 299, 286 Hz), 169.59, 169.62.
19F NMR (470 MHz, CDCl3): d = 89.0 (d, JF,F = 22 Hz, 0.6 F), 89.5
(d, JF,F = 21 Hz, 0.4 F), 90.3 (d, JF,F = 22 Hz, 0.6 F), 91.2 (d,
JF,F = 21 Hz, 0.4 F).
HRMS (ESI+): m/z calcd for C13H15F2INO2 [M + H]+: 382.0116;
1,1-Difluoro-2-iodo-4-methyl-4-phenylpent-1-en-3-yl Acetate
(3e)
Prepared from 1,1,1-trifluoro-2-iodoethane (840 mg, 4.00 mmol);
yield: 83%; colorless liquid.
found: 382.0117.
Methyl 2-(3-Acetoxy-5,5-difluoro-4-iodopent-4-en-1-yl)ben-
zoate (3h)
Prepared from 1,1,1-trifluoro-2-iodoethane (840 mg, 4.00 mmol);
yield: 82%; pale yellow liquid.
IR (ATR): 2976, 1745, 1709, 1498, 1442, 1369, 1265, 1219, 1030,
980, 768, 698, 609 cm–1.
IR (ATR): 3068, 2952, 1747, 1716, 1435, 1373, 1259, 1228, 1088,
1026, 966, 712 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.46 (s, 3 H), 1.48 (s, 3 H), 2.05
(s, 3 H), 5.14 (dd, J = 1.9, 1.0 Hz, 1 H), 7.24 (t, J = 7.7 Hz, 1 H),
7.32 (dd, J = 7.7, 7.7 Hz, 2 H), 7.40 (d, J = 7.7 Hz, 2 H).
13C NMR (126 MHz, CDCl3): d = 20.8, 24.9, 25.0 (d, JC,F = 9 Hz),
42.8, 48.0 (dd, JC,F = 25, 25 Hz), 74.5 (d, JC,F = 2 Hz), 126.7, 127.0,
128.0, 144.4, 153.8 (dd, JC,F = 298, 286 Hz), 169.3.
19F NMR (470 MHz, CDCl3): d = 91.1 (d, JF,F = 23 Hz, 1 F), 91.3
(d, JF,F = 23 Hz, 1 F).
HRMS (ESI+): m/z calcd for C14H15F2IO2 + Na [M + Na]+:
1H NMR (500 MHz, CDCl3): d = 1.86–1.92 (m, 1 H), 2.04–2.13 (m,
1 H), 2.08 (s, 3 H), 2.90 (ddd, J = 15.5, 10.0, 5.5 Hz, 1 H), 2.98 (ddd,
J = 15.5, 10.0, 5.5 Hz, 1 H), 3.91 (s, 3 H), 5.02 (ddt, J = 7.0, 2.0, 2.0
Hz, 1 H), 7.24 (d, J = 7.5 Hz, 1 H), 7.28 (dd, J = 7.5, 1.0 Hz, 1 H),
7.44 (td, J = 7.5, 1.5 Hz, 1 H), 7.91 (dd, J = 7.5, 1.4 Hz, 1 H).
13C NMR (126 MHz, CDCl3): d = 20.9, 29.7, 36.2, 52.0, 53.9 (t,
JC,F = 26 Hz), 69.2 (d, JC,F = 4 Hz), 126.4, 129.4, 130.9, 131.0,
132.2, 142.3, 154.0 (dd, JC,F = 299, 286 Hz), 167.7, 169.7.
19F NMR (470 MHz, CDCl3): d = 89.1 (d, JF,F = 23 Hz, 1 F), 89.9
(d, JF,F = 23 Hz, 1 F).
HRMS (ESI+): m/z calcd for C15H15F2IO4 + Na [M + Na]+:
402.9982; found: 403.0012.
1,1-Difluoro-2-iodo-5-phenylhex-1-en-3-yl Acetate (3f)
Prepared from 1,1,1-trifluoro-2-iodoethane (840 mg, 4.00 mmol);
yield: 81% (diastereomer ratio = 6:4); colorless liquid.
446.9881; found: 446.9879.
IR (ATR): 3028, 2962, 1747, 1716, 1495, 1452, 1371, 1269, 1225,
1020, 978, 700 cm–1.
1,1-Difluoro-2-iodo-3-methyl-5-phenylpent-1-en-3-yl Acetate
(3i)
To a THF (5 mL) solution of (i-Pr)2NH (1.1 mL, 8.00 mmol) was
added BuLi (4.8 mL, 1.67 M in hexane, 8.0 mmol) over 10 min at
0 °C under argon. The resulting solution was allowed to stir for an
additional 15 min, then cooled to –93 °C using a cold hexane bath.
To this cold LDA solution was added a THF (2 mL) solution of
1H NMR (500 MHz, CDCl3): d = 1.28 (d, J = 7.0 Hz, 1.8 H), 1.29
(d, J = 7.0 Hz, 1.2 H), 1.80–1.88 (m, 1 H), 1.95 (s, 1.8 H), 1.98–2.05
(m, 0.4 H), 2.06 (s, 1.2 H), 2.06–2.12 (m, 0.6 H), 2.62–2.69 (m, 0.6
H), 2.70–2.78 (ddq, J = 7.0, 7.0, 7.0 Hz, 0.4 H), 4.78 (dd, J = 6.5,
6.5 Hz, 0.6 H), 4.84 (dd, J = 7.5, 7.5 Hz, 0.4 H,), 7.16 (dd, J = 7.0,
Synthesis 2011, No. 6, 881–886 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,1-Difluoroallenes
885
CF3CH2I (840 mg, 4.00 mmol) over 10 min, keeping the tempera-
ture between –93 and –85 °C. After stirring for 20 min at the same
temperature, a THF (2 mL) solution of 4-phenylbutan-2-one (593
mg, 4.00 mmol) was added over 5 min, keeping the temperature be-
tween –93 and –85 °C. The mixture was stirred for an additional 30
min, then warmed to –30 °C over 90 min. The reaction was
quenched with sat. aq NH4Cl (15 mL), and the product was extract-
ed with Et2O (3 × 15 mL). The combined organic layers were
washed with brine (15 mL) and dried (Na2SO4). After removal of
the solvent under reduced pressure, the residue was purified by col-
umn chromatography (hexane–EtOAc, 10:1). This alcohol was used
in the next step without further purification. To a solution of the al-
cohol in isopropenyl acetate (3 mL) was added 4-methylbenzene-
sulfonic acid monohydrate (5 mg, 0.03 mmol). After refluxing for 4
h, the reaction was quenched with sat. aq NaHCO3 (15 mL). The
products were extracted with Et2O (3 × 15 mL). The combined or-
ganic layers were washed with brine (15 mL) and dried (Na2SO4).
After removal of the solvent under reduced pressure, the residue
was purified by column chromatography (hexane–EtOAc, 30:1).
Acetate 3i was obtained as a colorless liquid (1.22 g, 80%, two
steps).
1H NMR (500 MHz, CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.27–1.30
(m, 12 H), 1.49 (tq, J = 7.5, 7.0 Hz, 2 H), 2.23 (ttd, J = 7.0, 6.3, 6.0
Hz, 2 H), 6.42 (tt, J = 6.3 Hz, JH,F = 2.3 Hz, 1 H).
13C NMR (126 MHz, CDCl3): d = 14.1, 22.7, 27.6, 28.9, 29.3, 29.4,
29.5, 31.9, 32.3 (t, JC,F = 2 Hz), 122.5 (t, JC,F = 6 Hz), 152.5 (t,
JC,F = 261 Hz), 169.3 (t, JC,F = 36 Hz).
19F NMR (470 MHz, CDCl3): d = 59.4 (td, JF,H = 6, 3 Hz, 2 F).
HRMS (EI): m/z calcd for C12H20F2 [M]+: 202.1533; found:
202.1516.
1,1-Difluoro-5-(1-naphthyl)penta-1,2-diene (1c)
Prepared from 3c (416 mg, 1.00 mmol); yield: 82%; colorless liq-
uid.
IR (ATR): 3062, 2941, 2009, 1745, 1458, 1186, 791 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.48–2.54 (m, 2 H), 3.09 (t, J = 7.4
Hz, 2 H), 6.36 (tt, J = 6.1 Hz, JH,F = 2.4 Hz, 1 H), 7.16 (d, J = 6.6
Hz, 1 H), 7.25 (dd, J = 7.6 Hz, 1 H), 7.32–7.39 (m, 2 H), 7.59 (d,
J = 7.5 Hz, 1 H), 7.72 (d, J = 8.0 Hz, 1 H), 7.83 (d, J = 7.5 Hz, 1 H).
13C NMR (126 MHz, CDCl3): d = 30.8, 33.0, 121.6 (t, JC,F = 5.5
Hz), 123.4, 125.5, 125.6, 126.0, 126.1, 127.1, 128.9, 131.6, 133.9,
136.6, 152.9 (t, JC,F = 261 Hz), 170.0 (t, JC,F = 36 Hz).
IR (ATR): 3028, 2931, 2862, 1790, 1741, 1712, 1496, 1454, 1369,
1238, 1196, 1068, 1020, 700 cm–1.
19F NMR (470 MHz, CDCl3): d = 60.4 (dt, JF,H = 2, 5 Hz, 2 F).
HRMS (EI): m/z calcd for C15H12F2 [M]+: 230.0907; found:
1H NMR (500 MHz, CDCl3): d = 1.87 (d, J = 4.6 Hz, 1 H), 2.04 (s,
3 H), 2.11–2.23 (m, 2 H), 2.58 (t, J = 8.6 Hz, 2 H), 7.18–7.20 (m, 3
H), 7.29 (dd, J = 7.0, 7.0 Hz, 2 H).
13C NMR (126 MHz, CDCl3): d = 21.8, 22.9 (d, JC,F = 7 Hz), 30.0,
42.8 (dd, JC,F = 2 Hz), 59.7 (dd, JC,F = 26, 22 Hz), 80.6 (d, JC,F = 3
Hz), 126.1, 128.3, 128.5, 140.8, 152.5 (dd, JC,F = 301, 281 Hz),
169.3.
230.0906.
5-(4-tert-Butylphenyl)-1,1-difluoro-4-methylpenta-1,2-diene
(1d)
Prepared from 3d (436 mg, 1.00 mmol); yield: 92%; colorless liq-
uid.
19F NMR (470 MHz, CDCl3): d = 89.0 (dq, JF,F = 33 Hz, JF,H = 5 Hz,
1 F), 97.3 (d, JF,F = 33 Hz, 1 F).
IR (ATR): 2964, 2870, 2009, 1446, 1238, 1190, 937, 858 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.05 (d, J = 6.6 Hz, 3 H), 1.30 (s,
9 H), 2.57 (dd, J = 13.0, 6.6 Hz, 1 H), 2.59–2.68 (m, 1 H), 2.75 (dd,
J = 13.0, 7.6 Hz, 1 H), 6.41 (ddd, J = 5.0 Hz, JH,F = 2.5, 2.5 Hz, 1
H), 7.08 (d, J = 8.0 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H).
13C NMR (126 MHz, CDCl3): d = 18.5, 31.4, 34.3, 38.4, 41.6 (d,
JC,F = 2 Hz), 125.2, 127.1 (dd, JC,F = 6, 6 Hz), 128.8, 136.4, 149.1,
153.5 (dd, JC,F = 261, 261 Hz), 168.6 (dd, JC,F = 36, 36 Hz).
19F NMR (470 MHz, CDCl3): d = 60.0 (ddd, JF,F = 127 Hz, JF,H = 3,
3 Hz, 1 F), 60.3 (ddd, JF,F = 127 Hz, JF,H = 3, 3 Hz, 1 F).
HRMS (EI): m/z calcd for C16H20F2 [M]+: 250.1533; found:
HRMS (ESI+): m/z calcd for C14H15F2IO2 + Na [M + Na]+:
402.9982; found: 402.9979.
1,1-Difluoro-5-phenylpenta-1,2-diene (1a); Typical Procedure
To a suspension of Zn powder (131 mg, 2.00 mmol) in DMF (3 mL)
was added a DMF (2 mL) solution of 3a (366 mg, 1.00 mmol) at r.t.
under argon. After stirring for 3 h, the resulting reaction mixture
was filtered to remove the excess Zn and then diluted with Et2O (20
mL) and brine (15 mL). The products were extracted with Et2O
(3 × 15 mL). The combined organic layers were washed with brine
(15 mL) and dried (Na2SO4). After removal of the solvent under re-
duced pressure, the residue was purified by column chromatogra-
phy (pentane). Allene 1a was obtained as a colorless liquid (155 mg,
86%).
250.1532.
1,1-Difluoro-4-methyl-4-phenylpenta-1,2-diene (1e)
IR (ATR): 3030, 2929, 2362, 2013, 1462, 1196, 744, 698 cm–1.
Prepared from 3e (380 mg, 1.00 mmol); yield: 93%; colorless liq-
uid.
1H NMR (500 MHz, CDCl3): d = 2.53–2.61 (m, 2 H), 2.81 (t,
J = 7.5 Hz, 2 H), 6.47 (tt, J = 6.1 Hz, JH,F = 2.4 Hz, 1 H), 7.17–7.22
(m, 3 H), 7.30 (dd, J = 7.3, 7.3 Hz, 2 H).
13C NMR (126 MHz, CDCl3): d = 33.76, 33.77, 121.4 (t, JC,F = 6
Hz), 126.2, 128.4, 128.5, 140.6, 152.8 (t, JC,F = 261 Hz), 170.1 (t,
JC,F = 36 Hz).
19F NMR (470 MHz, CDCl3): d = 60.0 (td, JF,H = 5, 2 Hz, 2 F).
HRMS (EI): m/z calcd for C11H10F2 [M]+: 180.0751; found:
IR (ATR): 2972, 2931, 2873, 2009, 1601, 1495, 1435, 1192, 958,
854, 760, 696 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.47 (s, 6 H), 6.55 (t, JH,F = 2.8 Hz,
1 H), 7.23–7.25 (m, 1 H), 7.31–7.36 (m, 4 H).
13C NMR (126 MHz, CDCl3): d = 28.0, 42.4 (dd, JC,F = 2 Hz),
125.9, 126.6, 128.5, 131.0 (t, JC,F = 6 Hz), 146.2 (d, JC,F = 2 Hz),
153.3 (dd, JC,F = 262, 262 Hz), 167.1 (dd, JC,F = 36, 36 Hz).
19F NMR (470 MHz, CDCl3): d = 61.1 (d, JH,F = 2 Hz, 2 F).
HRMS (EI): m/z calcd for C12H12F2 [M]+: 194.0907; found:
194.0903.
180.0749.
1,1-Difluorododeca-1,2-diene (1b)
Prepared from 3b (388 mg, 1.00 mmol); yield: 87%; colorless liq-
uid.
1,1-Difluoro-5-phenylhexa-1,2-diene (1f)
IR (ATR): 2925, 2856, 2011, 1462, 1246, 1194, 721 cm–1.
Prepared from 3f (380 mg, 1.00 mmol); yield: 95%; colorless liquid.
IR (ATR): 3030, 2964, 2009, 1726, 1603, 1495, 1458, 1240, 1190,
760, 698 cm–1.
Synthesis 2011, No. 6, 881–886 © Thieme Stuttgart · New York

886
K. Oh et al.
PAPER
1H NMR (500 MHz, CDCl3): d = 1.30 (d, J = 7.0 Hz, 3 H), 2.44–
2.60 (m, 2 H), 2.95 (qdd, J = 7.1, 7.1, 7.1 Hz, 1 H), 6.28 (dddd,
J = 6.9, 6.9 Hz, JH,F = 2.4, 2.4 Hz, 1 H), 7.18–7.23 (m, 3 H), 7.30 (t,
J = 6.5 Hz, 2 H).
13C NMR (126 MHz, CDCl3): d = 21.6, 38.8, 40.7, 120.4 (dd,
JC,F = 6, 6 Hz), 126.4, 126.9, 128.5, 145.7, 152.4 (dd, JC,F = 260,
260 Hz), 170.9 (dd, JC,F = 36, 36 Hz).
Acknowledgment
This research was supported by a Grant-in-Aid for Scientific
Research from the Japan Society for the Promotion of Science, The
Asahi Glass Foundation, and Du Pont–Mitsui Fluorochemicals Co.,
Ltd. We are grateful to Tosoh F-Tech, Inc. for a generous gift of
1,1,1-trifluoro-2-iodoethane.
19F NMR (470 MHz, CDCl3): d = 59.1 (br ddd, JF,F = 122 Hz,
JF,H = 6, 4 Hz, 1 F), 59.6 (br ddd, JF,F = 122 Hz, JF,H = 7, 4 Hz, 1 F).
References
HRMS (EI): m/z calcd for C12H12F2 [M]+: 194.0907; found:
194.0906.
(1) (a) Dolbier, W. R. Jr.; Burkholder, C. R.; Piedrahita, C. A.
J. Fluorine Chem. 1982, 20, 637. (b) Dolbier, W. R. Jr.;
Burkholder, C. R.; Winchester, W. R. J. Org. Chem. 1984,
49, 1518. (c) Dolbier, W. R. Jr.; Burkholder, C. R. Israel J.
Chem. 1985, 26, 115. (d) Dolbier, W. R. Jr.; Wicks, G. E.;
Burkholder, C. R. J. Org. Chem. 1987, 52, 2196.
(e) Dolbier, W. R. Jr.; Burkholder, C. R.; Wicks, G. E.;
Palenik, G. J.; Gawron, M. J. Am. Chem. Soc. 1985, 107,
7183. (f) Dolbier, W. R. Jr. Acc. Chem. Res. 1991, 24, 63.
(2) (a) Dolbier, W. R. Jr.; Wicks, G. E. J. Am. Chem. Soc. 1985,
107, 3626. (b) Shen, Q.; Hammond, G. B. J. Am. Chem. Soc.
2002, 124, 6534.
(3) (a) Mae, M.; Hong, J. A.; Xu, B.; Hammond, G. B. Org. Lett.
2006, 8, 479. (b) Xu, Y.-Y.; Jin, F.-Q.; Huang, W.-Y.
J. Fluorine Chem. 1995, 70, 5.
(4) (a) Blomquist, A. T.; Longone, D. T. J. Am. Chem. Soc.
1957, 79, 4981. (b) Knoth, W. H.; Coffman, D. D. J. Am.
Chem. Soc. 1960, 82, 3873.
3-(5,5-Difluoro-2-methylpenta-3,4-dien-1-yl)pyridine (1g)
Prepared from 3g (381 mg, 1.00 mmol); yield: 71%; colorless liq-
uid.
IR (ATR): 2970, 2931, 2009, 1576, 1446, 1188, 1026, 939, 856,
796, 714 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.09 (d, J = 8.0 Hz, 3 H), 2.60–
2.72 (m, 2 H), 2.81 (dd, J = 12.7, 6.0 Hz, 1 H), 6.42 (dt, J = 8.0 Hz,
JH,F = 2.6 Hz, 1 H), 7.23 (ddd, J = 7.8, 4.8, 0.6 Hz, 1 H), 7.49 (ddd,
J = 7.8, 2.1, 1.9 Hz, 1 H), 8.45 (d, J = 1.9 Hz, 1 H), 8.48 (dd,
J = 4.8, 1.5 Hz, 1 H).
13C NMR (101 MHz, CDCl3): d = 18.5, 38.0 (t, JC,F = 2 Hz), 38.9 (t,
JC,F = 2 Hz), 123.3, 126.0 (t, JC,F = 6 Hz), 134.8, 136.5, 147.7,
150.3, 153.4 (t, JC,F = 262 Hz), 169.4 (t, JC,F = 36 Hz).
19F NMR (376 MHz, CDCl3): d = 60.5 (d, J = 120 Hz, 1 F), 60.7 (d,
J = 120 Hz, 1 F).
HRMS (ESI+): m/z calcd for C11H12F2N [M + H]+: 196.0938; found:
(5) (a) Shi, G.; Xu, Y. J. Fluorine Chem. 1989, 44, 161.
(b) Wang, Z. G.; Hammond, G. B. J. Org. Chem. 2000, 65,
6547. (c) Shen, Q.; Hammond, G. B. Org. Lett. 2001, 3,
2213. (d) Xu, B.; Hammond, G. B. Angew. Chem. Int. Ed.
2008, 47, 689.
196.0947.
Methyl 2-(5,5-Difluoropenta-3,4-dien-1-yl)benzoate (1h)
Prepared from 3h (424 mg, 1.00 mmol); yield: 74%; colorless liq-
uid.
(6) Yokota, M.; Fuchibe, K.; Ueda, M.; Mayumi, Y.; Ichikawa,
J. Org. Lett. 2009, 11, 3994.
(7) For the generation of 2,2-difluoro-1-tosyloxyvinyllithium
[F2C=C(OTs)Li], see: (a) Tanaka, K.; Nakai, T.; Ishikawa,
N. Tetrahedron Lett. 1978, 19, 4809. (b) Ichikawa, J.;
Hamada, S.; Sonoda, T.; Kobayashi, H. Tetrahedron Lett.
1992, 33, 337.
IR (ATR): 2952, 2009, 1716, 1460, 1254, 1186, 1130, 1082, 962,
748, 708 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.54–2.59 (m, 2 H), 3.13 (t,
J = 7.5 Hz, 2 H), 3.88 (s, 3 H), 6.49 (tt, J = 6.0 Hz, JH,F = 2.5 Hz, 1
H), 7.24 (d, J = 7.5 Hz, 1 H), 7.27 (dt, J = 7.5, 1.0 Hz, 1 H), 7.42
(td, J = 7.5, 1.5 Hz, 1 H), 7.92 (dd, J = 7.5, 1.5 Hz, 1 H).
13C NMR (126 MHz, CDCl3): d = 32.6, 33.9, 51.9, 121.6 (t, JC,F = 6
Hz), 126.3, 129.3, 130.9, 131.1, 132.1, 142.6, 152.6 (t, JC,F = 261
Hz), 167.7, 169.7 (t, JC,F = 36 Hz).
19F NMR (470 MHz, CDCl3): d = 60.0 (s, 2 F).
(8) For the generation of 2,2-difluoro-1-halovinyllithium
(F2C=CXLi), see: (a) (X = F): Burdon, J.; Coe, P. L.;
Haslock, I. B.; Powell, R. L. Chem. Commun. 1996, 49.
(b) (X = F): Burdon, J.; Coe, P. L.; Haslock, I. B.; Powell, R.
L. J. Fluorine Chem. 1999, 99, 127. (c) (X = Cl): Burdon,
J.; Coe, P. L.; Haslock, I. B.; Powell, R. L. J. Fluorine Chem.
1997, 85, 151. (d) (X = F or Cl): Coe, P. L.; Burdon, J.;
Haslock, I. B. J. Fluorine Chem. 2000, 102, 43.
(9) For the generation of 2,2-difluoro-1-halovinylzinc(II)
chloride (F2C=CXZnCl) at r.t., see: (a) (X = F): Anilkumar,
R.; Burton, D. J. Tetrahedron Lett. 2002, 43, 2731.
(b) (X = Cl): Anilkumar, R.; Burton, D. J. Tetrahedron Lett.
2002, 43, 6979. (c) (X = Br): Anilkumar, R.; Burton, D. J.
J. Fluorine Chem. 2004, 125, 561. (d) (X = I): Anilkumar,
R.; Burton, D. J. J. Fluorine Chem. 2005, 126, 455.
(10) The lithiation of CF3CH2I with BuLi instead of LDA at
–93 to –85 °C led to a low yield of 2,2-difluoro-1-iodovinyl-
lithium, probably due to I–Li exchange reaction.
(11) For 2-bromo-3,3-difluoroallylic acetates, zinc-promoted
1,2-elimination also took place readily at r.t. and led to the
formation of the corresponding 1,1-difluoroallenes.
(12) Mg was employed in THF to promote the 1,2-elimination of
acetate 3d in vain.
HRMS (EI): m/z calcd for C13H12F2O2 [M]+: 238.0805; found:
238.0805.
1,1-Difluoro-3-methyl-5-phenylpenta-1,2-diene (1i)
Prepared from 3i (380 mg, 1.00 mmol); yield: 86%; colorless liquid.
IR (ATR): 3064, 2922, 2360, 2004, 1801, 1604, 1481, 1173, 1043,
995, 696 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.91 (t, J = 5.0 Hz, 3 H), 2.40–
2.48 (m, 2 H), 2.74 (t, J = 8.2 Hz, 2 H), 7.13–7.18 (m, 3 H), 7.25 (t,
J = 7.6 Hz, 2 H).
13C NMR (126 MHz, CDCl3): d = 22.8, 33.4, 38.6, 126.1, 128.3,
128.4, 132.3 (t, JC,F = 6 Hz), 141.0, 150.4 (t, JC,F = 260 Hz), 163.0
(t, JC,F = 35 Hz).
19F NMR (470 MHz, CDCl3): d = 61.5 (tq, J = 5, 5 Hz, 2 F).
(13) When THF was used as a solvent, only a trace amount of 1g
was observed by the 19F NMR measurement in spite of a
large excess amount of Zn and an extended reaction time. A
similar behavior was exhibited by some other acetates 3
without a heteroaromatic ring.
HRMS (EI): m/z calcd for C12H12F2 [M]+: 194.0907; found:
194.0909.
Synthesis 2011, No. 6, 881–886 © Thieme Stuttgart · New York