A convenient route to synthesize N-protected α,α- difluorohomoallylic amines by gem-difluoroallylation of α-amido sulfones

Article abstract of DOI:10.1055/s-0028-1083220

A simple, mild, and efficient synthesis of α,α- difluorohomoallylic amines was achieved by the gem-difluoroallylation of α-amido sulfones with zinc powder. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1083220

PAPER
3805
A Convenient Route to Synthesize N-Protected a,a-Difluorohomoallylic
Amines by gem-Difluoroallylation of a-Amido Sulfones
g
em
-
Difluoroall
h
ylation of
a
-
e
A
midoSul
n
f
ones g-Feng Xie,a Zhuo Chai,b Gang Zhao,*b Ji-De Wang*a
a
Education Ministry Key Laboratory of Oil & Gas Fine Chemicals, Xinjiang University, Urumqi 830046, P. R. of China
E-mail: awangjdl@xju.edu.cn
b
Key Laboratory of Organofluorine Chemistry and Laboratory of Modern Synthetic Organic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: zhaog@mail.sioc.ac.cn
Received 10 June 2008; revised 28 August 2008
On the other hand, a-amidoalkyl phenyl sulfones, the pre-
cursors for the preparation of N-acylimines, are easily ac-
cessible and much less moisture-sensitive reagents than
N-acylimines. Therefore, the use of a-amidoalkyl phenyl
sulfones as substitutes for N-acyliminines has attracted
much attention in organic synthesis recently.6 Herein, we
would like to describe the first preparation of gem-difluo-
rohomoallyl amines directly from gem-difluoroallyl bro-
mide and a-amido sulfones in the presence of activated
zinc powder, in high yields and under mild conditions.
With a-amidoalkyl phenyl sulfone 1a (R1 = Ph; R2 = Boc)
as the model substrate and zinc powder as the promoter,
the initial experiments were performed at room tempera-
ture (Table 1). Under these conditions, the effects of a va-
riety of solvents were investigated first, and the results are
shown in Table 1. When tetrahydrofuran, which had
proved to be a suitable solvent for the gem-difluoroallyla-
tion of carbonyl compounds,3 was used, the desired prod-
uct 3a was obtained in only 35% yield (Table 1, entry 1).
The less polar solvent diethyl ether gave a much lower
yield (Table 1, entry 5). Gratifyingly, when this reaction
was run in N,N-dimethylformamide, the desired product
3a could be obtained in almost quantitative yield (Table 1,
entry 2). Other organic solvents such as ethanol and ace-
tonitrile were also studied, but gave poor yields (Table 1,
Abstract: A simple, mild, and efficient synthesis of a,a-difluoro-
homoallylic amines was achieved by the gem-difluoroallylation of
a-amido sulfones with zinc powder.
Key words: fluorine compounds, allylations, amines, amido sul-
fones, zinc, ring-closing metathesis
It is well known that the introduction of a fluorine atom
may often lead to great changes in the physicochemical
and biological properties of a molecule. The synthesis of
fluorine-containing organic compounds constitutes an im-
portant field in organic synthesis and pharmaceutical
chemistry.1 The difluoromethylene moiety (CF2), in par-
ticular, has been found to be a highly useful structural unit
in a great number of fluorinated compounds with special
bioactivity and medicinal potential, mainly due to its
unique properties as an isopolar–isosteric substitute for
oxygen to modify the bioactivities of some drug candi-
dates.2 Therefore, as a convenient way to introduce this
useful unit into organic compounds, the gem-difluoroally-
lation of carbonyl compounds, which could produce syn-
thetically and medicinally useful gem-difluorohomoallyl
alcohols, has been one of the research focuses of organo-
fluorochemistry.3 In 1991, Burton et al. reported a simple
procedure mediated by acid-washed zinc powder for the
gem-difluoroallylation of aldehydes and ketones with 3-
bromo-3,3-difluoropropene, which gave the correspond-
ing gem-difluorohomoallyl alcohols in moderate yields.4
Subsequently, the Kirihara group found that indium was
also a highly efficient promoter for the gem-difluoroally-
lation of aldehydes under mild reaction conditions.3j
However, compared to this well-developed gem-difluoro-
allylation of carbonyl compounds, to the best of our
knowledge, the gem-difluoroallylation of imines is almost
unknown despite the fact that the resulting gem-difluoro-
homoallylic amines are also very important compounds in
organic synthesis and medicinal chemistry.3f,i,5 This is
probably partly because imines are often less reactive and
more moisture-sensitive than the corresponding carbonyl
compounds.
Table 1 Screening of Solventsa
Boc
Boc
HN
HN
Ph
Br
Zn powder
DMF
Ph
F
F
SO2Ph
F
F
1a
2
3a
Entry
Solvent
THF
Yieldb (%)
1
2
3
4
5
6
35
DMF
EtOH
MeCN
Et2O
99
trace
18
11
H2O
trace
SYNTHESIS 2008, No. 23, pp 3805–3809
x
x.
x
x
.
2
0
0
8
a Reagents and conditions: 1a (1 equiv), 2 (1.5 equiv), Zn (2.5 equiv),
r.t., 3 h.
Advanced online publication: 14.11.2008
DOI: 10.1055/s-0028-1083220; Art ID: F13008SS
© Georg Thieme Verlag Stuttgart · New York
b Isolated yield after column chromatography.

3806
Z.-F. Xie et al.
PAPER
entries 3 and 4). Additionally, the reaction was completely Piperidine-derived heterocycles are ubiquitous substruc-
inhibited when performed in water (Table 1, entry 6).
tures in many natural and synthetic products with impor-
tant biological and pharmaceutical properties, and
therefore many efforts have been directed towards the
synthesis of these compounds.7 Hence, as a demonstration
of the utility of this gem-difluoroallylation reaction of a-
amido sulfones and the accompanying products, 3a was
converted into 5,8 a fluorous counterpart of piperidine-
derived heterocycles, in two steps involving a ring-
closing-metathesis reaction;9 5 was obtained in moderate
yield (Scheme 1).
With the optimal reaction conditions in hand, we tested
the generality of this gem-difluoroallylation reaction with
a series of a-amidoalkyl phenyl sulfones 1a–k (Table 2).
Generally, all the examined a-amidoalkyl phenyl sulfones
1 containing a phenyl R1 group, with electron-donating
groups (EDG) or electron-withdrawing groups (EWG) on
the phenyl ring, gave the desired products in high yields
(Table 2, entries 1–6). In addition, the heterocyclic 3-py-
ridyl sulfone 1g also proved to be a suitable substrate for
this transformation (Table 2, entry 7). Notably, the gem- In conclusion, a simple, mild, and efficient synthesis of
difluoroallylation of the a-alkyl-a-amidoalkyl phenyl sul- a,a-difluorohomoallylic amines was achieved in good to
fone 1h also provided a good yield (82%; Table 2, entry high yields by the gem-difluoroallylation of a-amido sul-
8). Moreover, when the N-protecting group R2 was fones mediated by zinc powder under mild reaction con-
changed to benzyloxycarbonyl, the reaction still proceed- ditions. This method could be applied to the synthesis of
ed smoothly to give the desired products, albeit with natural-like products containing the difluoromethylene
slightly lower yields (Table 2, entries 9–11). It is worth group. Efforts in this field are currently underway in our
pointing out that this reaction can be scaled up to at least laboratory and will be reported in due course.
2 mmol.
Zinc powder was purchased from Bodi Chemical Company (Tian-
Table 2 Scope of the Difluoroallylation of a-Amidoalkyl Phenyl
jing) and activated by washing with dilute aqueous HCl solution. a-
Amido sulfones were prepared according to known procedures.6
DMF was purchased from Sinopharm Chemical Reagent Co. Ltd
(Shanghai) and dried by distilling over CaH2. Melting points were
Sulfonesa
R2
R2
HN
R1
HN
R1
determined on a SGW X-4 apparatus and were uncorrected. 1H, 13
C
Br
Zn powder
DMF
and 19F NMR were recorded on Varian EM-360A or Bruker DPX-
300 instruments. TMS was used as the internal standard for 1H and
13C NMR. CFCl3 was used as the external standard for 19F NMR.
ESI-MS was carried out on an Agilent LC/MSD and HRMS (ESI)
was carried out on a Bruker ApeXIII 7.0 TESLA FTMS. IR spectra
were determined on a Perkin-Elmer 983G instrument. Elemental
analyses were carried out by the analytical center of Shanghai Insti-
tute of Organic Chemistry.
F
F
SO2Ph
F
F
1a–k
2
3a–k
Entry
R1
Ph
R2
Product
3a
Yieldb (%)
1
2
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Boc
Cbz
Cbz
Cbz
99 (97c)
94
4-BrC6H4
Tol
3b
3c
gem-Difluoroallylation of a-Amido Sulfones; General Proce-
dure
3
87
4
2-BrC6H4
Tol
3d
3e
85
Prop-1-ene 2 (62.8 mg, 0.3 mmol) was added to a suspension of Zn
dust (32 mg, 0.5 mmol) in anhyd DMF (2 mL) at r.t. After the mix-
ture had stirred for 1 h, the appropriate a-amido sulfone 1 (0.2
mmol) in anhyd DMF (1 mL) was added dropwise. Stirring was
continued for 2 h and then the mixture was quenched by the addition
of sat. aq NH4Cl (0.8 mL) and extracted with CH2Cl2 (3 × 5 mL).
The combined organic layers were dried (MgSO4) and concentrated
under reduced pressure to furnish the crude product, which was pu-
rified by column chromatography (silica gel, PE–EtOAc); this af-
forded pure products 3a–k.
5
83
6
3-O2NC6H4
3-pyridyl
Pr
3f
76
7
3g
96
8
3h
3i
82
9
Ph
94
10
11
4-BrC6H4
Tol
3j
84
Compound 3a
White solid; mp 77–79 °C.
3k
78
IR (film): 3348, 3037, 2981, 1685, 1530, 1500, 1369, 704 cm–1.
a Reagents and conditions: 1 (1 equiv), 2 (1.5 equiv), Zn (2.5 equiv),
r.t., 3 h.
1H NMR (300 MHz, CDCl3): d = 7.35–7.25 (m, 5 H), 5.89–5.62 (m,
2 H), 5.46–5.43 (d, J = 10.5 Hz, 1 H), 5.31–5.28 (m, 1 H), 5.09–4.98
(m, 1 H), 1.42 (s, 9 H).
b Isolated yield after column chromatography.
c Yield on a 2 mmol scale.
F
Boc
Br
Grubbs II (5 mol%)
BocN
Ph
HN
F
0.0025 M
NaH, 0 °C
N
Ph
CH2Cl2, reflux
40 min
Ph
DMF
90%
Boc
F
F
F
F
56%
3a
4
5
Scheme 1
Synthesis 2008, No. 23, 3805–3809 © Thieme Stuttgart · New York

PAPER
gem-Difluoroallylation of a-Amido Sulfones
3807
13C NMR (75 MHz, CDCl3): d = 154.9, 135.5, 130.7 (t, J = 26 Hz),
128.5 (2 C), 128.4, 128.3 (2 C), 121.2 (t, J = 9 Hz), 121.0 (q,
J = 244 Hz), 80.3, 58.8 (t, J = 27 Hz), 28.3 (3 C).
1H NMR (300 MHz, CDCl3): d = 7.23–7.14 (dd, J = 7.8 Hz, 4 H),
5.86–5.63 (m, 2 H), 5.47–5.43 (d, J = 10.8 Hz, 1 H), 5.29–5.25 (m,
1 H), 5.08–4.94 (m, 1 H), 2.35 (s, 3 H), 1.42 (s, 9 H).
19F NMR (282 MHz, CDCl3): d = –106.87 (dd, JF,F = 260 Hz,
JF,H = 20 Hz), –108.83 (dd, JF,F = 260 Hz, JF,H = 20 Hz).
ESI-MS: m/z = 306 [M + Na]+.
13C NMR (75 MHz, CDCl3): d = 153.8, 137.2, 131.4, 129.7 (t,
J = 26 Hz), 128.1 (2 C), 127.1 (2 C), 120.3 (t, J = 9 Hz), 119.3 (q,
J = 244 Hz), 79.2, 57.4 (t, J = 26 Hz), 28.3 (3 C), 20.1.
19F NMR (282 MHz, CDCl3): d = –106.95 (dd, JF,F = 260 Hz,
JF,H = 12 Hz), –108.89 (dd, JF,F = 260 Hz, JF,H = 12 Hz).
Anal. Calcd for C15H19F2NO2: C, 63.59; H, 6.76; N, 4.94. Found: C,
63.50; H, 6.76; N, 5.02.
ESI-MS: m/z = 320 [M + Na]+.
Compound 3b
White solid; mp 125–126 °C.
IR (film): 3344, 3030, 2980, 1710, 1688, 1526, 1368, 886, 801 cm–1.
Anal. Calcd for C16H21F2NO2: C, 64.63; H, 7.12; N, 4.71. Found: C,
64.69; H, 7.18; N, 4.66.
Compound 3f
White solid; mp 89–91 °C.
IR (film): 3331, 3078, 2980, 1720, 1537, 1354, 871, 708 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.51–7.48 (d, J = 8.4 Hz, 2 H),
7.23–7.20 (d, J = 8.4 Hz, 2 H), 5.90–5.65 (m, 2 H), 5.51–5.47 (d,
J = 10.5 Hz, 1 H), 5.27 (br, 1 H), 5.03–4.99 (m, 1 H), 1.43 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 153.7, 133.4, 130.6 (2 C), 129.3,
128.9 (2 C), 121.5, 120.6 (t, J = 8 Hz), 118.0 (q, J = 244 Hz), 79.5,
57.3 (t, J = 27 Hz), 27.2 (3 C).
19F NMR (282 MHz, CDCl3): d = –106.61 (dd, JF,F = 260 Hz,
JF,H = 12.6 Hz), –108.92 (dd, JF,F = 260 Hz, JF,H = 12.6 Hz).
1H NMR (300 MHz, CDCl3): d = 8.24–8.20 (m, 2 H), 7.71–7.68 (d,
J = 10.8 Hz, 1 H), 7.59–7.53 (m, 1 H), 5.96–5.69 (m, 2 H), 5.58–
5.54 (d, J = 10.5 Hz, 1 H), 5.42–5.39 (d, J = 8.4 Hz, 1 H), 5.23–5.12
(m, 1 H), 1.43 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 154.6, 137.5, 133.0 (t, J = 26 Hz),
129.5 (2 C), 128.8, 128.6 (2 C), 122.4 (t, J = 9 Hz), 119.1 (q,
J = 244 Hz), 80.2, 59.0 (t, J = 27 Hz), 28.5 (3 C).
ESI-MS: m/z = 386 [M + Na + 2]+, 384 [M + Na]+.
Anal. Calcd for C15H18BrF2NO2: C, 49.74; H, 5.01; N, 3.87. Found:
C, 49.85; H, 5.00; N, 3.73.
19F NMR (282 MHz, CDCl3): d = –105.19 (dd, JF,F = 260 Hz,
JF,H = 15 Hz), –109.53 (dd, JF,F = 260 Hz, JF,H = 15 Hz).
Compound 3c
ESI-MS: m/z = 351 [M + Na]+.
White solid; mp 103–104 °C.
IR (film): 3343, 3005, 2982, 1688, 1515, 1369, 889, 807 cm–1.
Anal. Calcd for C15H18F2N2O4: C, 54.87; H, 5.53; N, 8.53. Found:
C, 54.92; H, 5.54; N, 8.46.
1H NMR (300 MHz, CDCl3): d = 7.26–7.22 (d, J = 10.2 Hz, 2 H),
6.89–6.85 (d, J = 10.2 Hz, 2 H), 5.89–5.62 (m, 2 H), 5.47–5.43 (d,
J = 10.5 Hz, 1 H), 5.22 (br, 1 H), 5.05–4.96 (m, 1 H), 3.80 (s, 3 H),
1.42 (s, 9 H).
Compound 3g
Colorless oil.
IR (film): 3345, 2964, 2933, 1709, 1507, 1174, 992 cm–1.
13C NMR (75 MHz, CDCl3): d = 158.5, 153.9, 129.7 (t, J = 28 Hz),
128.3 (2 C), 126.4, 120.0 (t, J = 9 Hz), 19.6 (q, J = 244 Hz), 112.8
(2 C), 79.2, 57.1 (t, J = 27 Hz), 54.2, 27.2 (3 C).
19F NMR (282 MHz, CDCl3): d = –107.10 (dd, JF,F = 260 Hz,
JF,H = 12 Hz), –108.85 (dd, JF,F = 260 Hz, JF,H = 12 Hz).
1H NMR (300 MHz, CDCl3): d = 5.96–5.83 (m, 1 H), 5.70–5.64 (m,
1 H), 5.49–5.45 (d, J = 10.2 Hz, 1 H), 4.51–4.47 (d, J = 10.2 Hz, 1
H), 3.99–3.90 (m, 1 H), 1.42–1.20 (m, 13 H), 0.94–0.89 (t, J = 6.9
Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 154.5, 129.9 (t, J = 26 Hz), 119.6
(t, J = 9 Hz), 120.6 (q, J = 244 Hz), 78.7, 58.8 (t, J = 25 Hz), 29.3,
27.2 (3 C), 17.7, 12.7.
ESI-MS: m/z = 336 [M + Na]+.
Anal. Calcd for C16H21F2NO3: C, 61.33; H, 6.76; N, 4.47. Found: C,
61.38; H, 6.75; N, 5.51.
19F NMR (282 MHz, CDCl3): d = –108.17 (dd, JF,F = 260 Hz,
JF,H = 10 Hz), –111.66 (dd, JF,F = 260 Hz, JF,H = 15 Hz).
Compound 3d
ESI-MS: m/z = 272 [M + Na]+.
White solid; mp 75 °C.
IR (film): 3459, 3267, 2978, 2927, 1707, 1498, 1367, 753 cm–1.
Anal. Calcd for C12H21F2NO2: C, 57.81; H, 8.49; N, 5.61. Found: C,
57.92; H, 8.56; N, 5.55.
1H NMR (300 MHz, CDCl3): d = 7.59–7.56 (d, J = 7.8 Hz, 1 H),
7.36–7.30 (m, 2 H), 7.22–7.16 (m, 1 H), 5.99–5.62 (m, 3 H), 5.48–
5.38 (m, 2 H), 1.43 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 154.7, 133.1, 130.3 (t, J = 26 Hz),
129.8 (2 C), 129.0, 127.7 (2 C), 127.4 (q, J = 244 Hz), 121.5 (t,
J = 9 Hz), 80.5, 57.2 (t, J = 25 Hz), 28.3 (3 C).
19F NMR (282 MHz, CDCl3): d = –107.36 (dd, JF,F = 260 Hz,
JF,H = 12 Hz), –108.27 (dd, JF,F = 260 Hz, JF,H = 12 Hz).
ESI-MS: m/z = 386 [M + Na + 2]+, 384 [M + Na]+.
Compound 3h
Colorless oil.
IR (film): 3345, 2964, 2933, 1709, 1507, 1174, 992 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.96–5.83 (m, 1 H), 5.70–5.64 (m,
1 H), 5.49–5.45 (d, J = 10.2 Hz, 1 H), 4.51–4.47 (d, J = 10.2 Hz, 1
H), 3.99–3.90 (m, 1 H), 1.42–1.20 (m, 13 H), 0.94–0.89 (t, J = 6.9
Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 154.5, 129.9 (t, J = 26 Hz), 119.6
(t, J = 9 Hz), 120.6 (q, J = 244 Hz), 78.7, 58.8 (t, J = 25 Hz), 29.3,
27.2 (3 C), 17.7, 12.7.
19F NMR (282 MHz, CDCl3): d = –108.17 (dd, JF,F = 260 Hz,
JF,H = 10 Hz), –111.66 (dd, JF,F = 260 Hz, JF,H = 15 Hz).
ESI-MS: m/z = 272 [M + Na]+.
Anal. Calcd for C15H18BrF2NO2: C, 49.74; H, 5.01; N, 3.87. Found:
C, 49.85; H, 5.06; N, 3.82.
Compound 3e
White solid; mp 95–97 °C.
IR (film): 3348, 3037, 2979, 2928, 1719, 1531, 1368, 889, 798 cm–1.
Anal. Calcd for C12H21F2NO2: C, 57.81; H, 8.49; N, 5.61. Found: C,
57.92; H, 8.56; N, 5.55.
Synthesis 2008, No. 23, 3805–3809 © Thieme Stuttgart · New York

3808
Z.-F. Xie et al.
PAPER
Compound 3i
White solid; mp 99 °C.
References
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IR (film): 3330, 3030, 2963, 1737, 1690, 1534, 1374, 1217, 703
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1H NMR (300 MHz, CDCl3): d = 7.32 (s, 5 H), 7.20–7.13 (m, 5 H),
5.83–5.57 (m, 3 H), 5.45–5.41 (d, J = 10.8 Hz, 1 H), 5.14–5.05 (m,
3 H).
13C NMR (75 MHz, CDCl3): d = 155.7, 136.0, 135.1, 130.5 (t,
J = 26 Hz), 129.0 (4 C), 128.6 (2 C), 128.5, 128.3 (3 C), 121.6 (t,
J = 9 Hz), 120.9 (q, J = 244 Hz), 67.4, 59.4 (t, J = 27 Hz).
19F NMR (282 MHz, CDCl3): d = –106.17 (dd, JF,F = 260 Hz,
JF,H = 12 Hz), –107.24 (dd, JF,F = 260 Hz, JF,H = 12 Hz).
ESI-MS: m/z = 340 [M + Na]+.
Anal. Calcd for C18H17F2NO2: C, 68.13; H, 5.40; N, 4.41. Found: C,
68.15; H, 5.46; N, 4.32.
Compound 3j
White solid; mp 107–108 °C.
IR (film): 3318, 3037, 2961, 1716, 1539, 1491, 1259, 798, 697 cm–1.
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3 H).
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Commun. 1999, 29, 235. (m) Qing, F.; Wan, D. Tetrahedron
1998, 54, 14189. (n) Kirihara, M.; Takuwa, T.; Takizawa,
S.; Momose, T. Tetrahedron Lett. 1997, 38, 2853.
(o) Arnone, A.; Bravo, P.; Viani, F.; Zanda, M.; Cavicchio,
G.; Crucianelli, M. J. Fluorine Chem. 1996, 76, 169.
(p) Patel, S. T.; Percy, J. M.; Wilkes, R. D. J. Org. Chem.
1996, 61, 166. (q) Morikawa, T.; Uejima, M.; Kobayashi, Y.
Chem. Lett. 1988, 1407. (r) Hiyama, T.; Obayashi, M.;
Sawahata, M. Tetrahedron Lett. 1983, 24, 4113.
13C NMR (75 MHz, CDCl3): d = 154.6, 134.7, 133.0, 130.7 (3 C),
129.0 (t, J = 26 Hz), 128.9 (2 C), 127.5 (2 C), 127.3, 127.2, 121.8,
120.9 (t, J = 9 Hz), 119.5 (q, J = 244 Hz), 66.4, 57.9 (t, J = 27 Hz).
19F NMR (282 MHz, CDCl3): d = –106.40 (dd, JF,F = 260 Hz,
JF,H = 12 Hz), –107.85 (dd, JF,F = 260 Hz, JF,H = 12 Hz).
ESI-MS: m/z = 420 [M + Na + 2]+, 418 [M + Na]+.
HRMS (ESI): m/z calcd for C18H16BrF2NO2Na: 418.0231; found:
418.0225.
Anal. Calcd for C18H16BrF2NO2: C, 54.56; H, 4.07; N, 3.54. Found:
C, 54.64; H, 4.16; N, 3.51.
Compound 3k
White solid; mp 102–104 °C.
IR (film): 3326, 3033, 2956, 1717, 1534, 1515, 1235, 796, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.33 (s, 5 H), 7.22–7.13 (m, 4 H),
5.84–5.56 (m, 3 H), 5.44–5.40 (d, J = 10.8 Hz, 1 H), 5.13–5.03 (m,
3 H), 2.33 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 154.6, 137.4, 134.9, 131.0, 129.5
(t, J = 26 Hz), 128.3 (4 C), 127.5, 127.2, 127.1, 126.9, 126.7, 120.4
(t, J = 9 Hz), 119.6 (q, J = 244 Hz), 66.3, 58.1 (t, J = 27 Hz), 20.1.
19F NMR (282 MHz, CDCl3): d = –107.17 (dd, JF,F = 260 Hz,
JF,H = 12 Hz), –108.24 (dd, JF,F = 260 Hz, JF,H = 12 Hz).
(s) Seyferth, D.; Simon, R. M.; Sepelak, D. J.; Klein, H. A.
J. Am. Chem. Soc. 1983, 105, 4634.
ESI-MS: m/z = 354 [M + Na]+.
(4) Yang, Z.; Burton, D. J. J. Org. Chem. 1991, 56, 1037.
(5) Ohba, T.; Ikeda, E.; Takei, H. Bioorg. Med. Chem. Lett.
1996, 6, 1875.
Anal. Calcd for C19H19F2NO2: C, 68.87; H, 5.78; N, 4.23. Found: C,
68.82; H, 5.97; N, 4.22.
(6) For a recent review, see: (a) Petrini, M. Chem. Rev. 2005,
105, 3949. For recent examples, see: (b) Lombardo, M.;
Mosconi, E.; Pasi, F.; Petrini, M.; Trombini, C. J. Org.
Chem. 2007, 72, 1834. (c) Mizuta, S.; Shibata, N.; Goto, Y.;
Furukawa, T.; Nakamura, S.; Toru, T. J. Am. Chem. Soc.
2007, 129, 6394. (d) Song, J.; Shih, H.-W.; Deng, L. Org.
Lett. 2007, 9, 603. (e) Shibasaki, M.; Matsunaga, S.
J. Organomet. Chem. 2006, 691, 2089. (f) Marques,
M. M. B. Angew. Chem. Int. Ed. 2006, 45, 348. (g) Fini, F.;
Bernardi, L.; Herrera, R. P.; Pettersen, D.; Ricci, A.;
Sgarzania, V. Adv. Synth. Catal. 2006, 348, 2043.
(h) Herrera, R. P.; Bernardi, L.; Fini, F.; Pettersen, D.; Ricci,
A. J. Org. Chem. 2006, 71, 9869.
Acknowledgment
The authors thank the National Natural Science Foundation of
China for financial support (No. 20562011).
Synthesis 2008, No. 23, 3805–3809 © Thieme Stuttgart · New York

PAPER
(7) For reviews, see: (a) Enders, D.; Thiebes, T. Pure Appl.
gem-Difluoroallylation of a-Amido Sulfones
(dd, J = 17.3, 25.1 Hz), 115.9 (t, J = 9 Hz), 120.6 (t,
3809
Chem. 2001, 73, 573. (b) Laschat, S.; Dickner, T. Synthesis
2000, 1781. For examples, see: (c) Agami, C.; Couty, F.;
Evano, G. Tetrahedron: Asymmetry 2000, 11, 4639.
(d) De Matteis, V.; van Delft, F. L.; Tiebes, J.; Rutjes, F. P.
J. T. Eur. J. Org. Chem. 2006, 1166. (e) Petukhov, P. A.;
Zhang, J.; Wang, C. Z.; Ye, Y. P.; Johnson, K. M.;
Kozikowski, A. P. J. Med. Chem. 2004, 47, 3009. (f) Amat,
M.; Lozano, O.; Escolano, C.; Molins, E.; Bosch, J. J. Org.
Chem. 2007, 72, 4431; and references cited therein.
J = 177.5 Hz), 81.2, 59.1, 40.6, 27.2 (3 C). 19F NMR (282
MHz, CDCl3): d = –79.56 (d, JF,F = 279.2 Hz), –103.24 (d,
JF,F = 297.2 Hz). MS (ESI): m/z = 318 [M + Na]+. HRMS
(EI): m/z calcd for C11H10NF2 [M+–Boc]: 194.0781; found:
194.0777.
(9) For recent examples of the application of RCM in olefins
bearing fluorine substituents, see: (a) Fustero, S.;
Fernández, B.; Sanz-Cervera, J. F.; Mateu, N.; Mosulén, S.;
Carbajo, R. J.; Pineda-Lucena, A.; de Arellano, C. R. J. Org.
Chem. 2007, 72, 8716. (b) Miles, J. A. L.; Mitchell, L.;
Percy, J. M.; Singh, K.; Uneyama, E. J. Org. Chem. 2007,
72, 1575. (c) Yang, Y.-Y.; Xu, J.; You, Z.-W.; Xu, X.-H.;
Qiu, X.-L.; Qing, F.-L. Org. Lett. 2007, 9, 5437. (d) You,
Z.-W.; Wu, Y.-Y.; Qing, F. L. Synthesis 2006, 2535.
(8) Characterization data for 5: colorless crystals; mp 96–97 °C.
IR (film): 2925, 2855, 1707, 1456, 1408, 1393, 1168, 1092,
698 cm–1. 1H NMR (300 MHz, CDCl3): d = 7.32 (m, 5 H),
6.26 (m, 1 H), 6.09 (m, 1 H), 5.74 (m, 1 H), 4.48–4.38 (m, 1
H), 3.56–3.47 (m, 13 H), 1.49 (s, 9 H). 13C NMR (75 MHz,
CDCl3): d = 154.1, 134.9, 133.6, 128.4, 128.2, 128.0, 122.1
Synthesis 2008, No. 23, 3805–3809 © Thieme Stuttgart · New York