Studies on highly regio- and stereoselective fluorohydroxylation reaction of 3-aryl-1,2-allenyl phosphine oxides with Selectfluor

Article abstract of DOI:10.1016/j.tet.2009.07.009

The fluorohydroxylation of allenyl phosphine oxides with Selectfluor in commercial MeCN without prior treatment or a mixed solvent of anhydrous MeCN (refluxed over CaH₂ and distilled before use) and 7.0 equiv of H₂O or MeNO₂

Full text of DOI:10.1016/j.tet.2009.07.009

Tetrahedron 65 (2009) 8035–8042
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Tetrahedron
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Studies on highly regio- and stereoselective fluorohydroxylation reaction
of 3-aryl-1,2-allenyl phosphine oxides with Selectfluor
*
*
Guangke He, Chunling Fu , Shengming Ma
Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 May 2009
Received in revised form 28 June 2009
Accepted 3 July 2009
Available online 8 July 2009
The fluorohydroxylation of allenyl phosphine oxides with Selectfluor in commercial MeCN without prior
treatment or a mixed solvent of anhydrous MeCN (refluxed over CaH2 and distilled before use) and 7.0
equiv of H2O or MeNO2/H2O¼10/1 afforded 2-fluoro-3-hydroxy-1(E)-alkenyl diphenyl phosphine oxides
in moderate yields with very high regio- and stereoselectivities. The E-stereoselectivity is believed to be
controlled by the phosphine oxide functionality. In the reaction of 3-(4-methoxyphenyl)-1,2-propadienyl
diphenyl phosphine oxide, further fluorination on the electron-rich phenyl ring was also observed.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
Table 1
Synthesis of 3-aryl-1,2-allenylic diphenyl phosphine oxides (1)7
Organofluorine compounds are playing a great role in phar-
maceuticals owing to their unique physical and biological prop-
erties.1,2 Similarly, organophosphorous compounds also show
synthetic potential.3a–g It is well known that monofluorination
towards organic molecules is not easy.4 Recently, we observed
that electrophilic reaction of some allenes provides an efficient
O
Ph P
Ph
R2
R3
R2
R3
pyridine, CH2Cl2/Et2O
0 °C ~ rt
R1
Ph2PCl
+
R1
OH
1.1 equiv
1
pathway for the monofluorination, for example, b-fluorolactoni-
Entry
R1
R2
R3
Isolated yield
zation of 1,2-allenoic acids5 and fluorohydroxylation of 3-aryl-1,2-
allenes.6 As a part of our research program aimed at exploring
novel synthetic methodology for producing mono-fluorinated
compounds, the electrophilic fluorination of 1,2-allenylic phos-
phine oxides is of interest to us. In this paper we wish to disclose
a highly regio- and stereoselective protocol of fluorohydroxylation
reaction of 3-aryl-1,2-allenylic phosphine oxides.
of 1 (%)
1
2
3
4
H
H
H
Me
Et
Ph
Me
Me
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
63 (1a)
55 (1b)
54 (1c)
45 (1d)
51 (1e)
75 (1f)
69 (1g)
58 (1h)
52 (1i)
68 (1j)
46 (1k)
44 (1l)
62 (1m)
54 (1n)
20 (1o)
n-C4H9
Ph
H
H
H
H
H
H
5
6
7a
8
4-NO2C6H4
4-FC6H4
4-ClC6H4
3-ClC6H4
2-ClC6H4
4-MeC6H4
Ph
9
10
11
12
13
14
15
2. Results and discussion
H
H
H
H
H
n-C4H9
Ph
H
It is well known that 3-aryl-1,2-allenylic diphenyl phosphine
oxides 1 can be easily prepared from the reaction of corresponding
propargylic alcohols with Ph2PCl.7 Thus, the starting materials used
in this studies were synthesized accordingly (Table 1). On the other
hand, among all kinds of electrophilic fluorination reagents, Selec-
fluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane-
bis(tetrafluoroborate) is an effective one because of its availability,
reliability, and mildness.8–10
Ph
H
4-MeOC6H4
a
The reaction was conducted at ꢁ40 ꢀC.
According to our previous experimental results on the elec-
trophilic reaction of allenes,5,6,11–14 MeCN/H2O was a good solvent
system for electrophilic addition reactions of allenes. When
a mixture of MeCN/H2O (10:1) was used as the solvent, 3-phe-
nylbuta-1,2-dienyl diphenyl phosphine oxide 1a reacted with 1.5
equiv of Selectfluor at 80 ꢀC to give 2-fluoro-3-hydroxy-3-phenyl-
1(E)-butenyl diphenyl phosphine oxide E-2a in moderate yield
together with the formation of 2-fluoro-3-phenylbuta-1(E),3-
* Corresponding authors.
E-mail addresses: fucl@zju.edu.cn (C. Fu), masm@mail.sioc.ac.cn (S. Ma).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.07.009

8036
G. He et al. / Tetrahedron 65 (2009) 8035–8042
Table 3
dienyl diphenyl phosphine oxide E-3a (entry 1, Table 2). Obvi-
ously, the ratio of E-2a/E-3a was not satisfactory. Considering the
hydroxyl group in E-2a was formed from the water in the reaction
medium, more water was added, however, the yield of E-2a and
the ratio of E-2a/E-3a were essentially the same (entries 2–3,
Table 2). The reaction in pure H2O afforded the products in much
lower yields with an E-2a/E-3a ratio of 95:5 (entry 4, Table 2).
Furthermore, the selectivity was not very much improved by
conducting the reaction at 60 ꢀC or even lower (entries 5–6, Table
2). Surprisingly, the fluorohydroxylation reaction in commercial
MeCN without prior treatment afforded E-2a exclusively in 66%
isolated yield, indicating that the trace amount of water in MeCN
is just enough for this transformation (entry 7, Table 2). In fact, it
was found that the reaction proceeded smoothly in anhydrous
MeCN (refluxed over CaH2 and distilled before use) in the pres-
ence of 7 equiv of H2O (entry 8, Table 2). Suitable amount of water
is providing the hydroxyl group in the product E-2a.
Fluorohydroxylation of differently substituted 1,2-propadienyl diphenyl phosphine
oxides 1 with Selectfluor
O
P
O
P
HO
Ph
Ph
R2
R3
Ph
R2
R3
conditions
80 °C
+
Ph
Selectfluor
1.5 equiv
R1
R1
F
E-2
1
Entry
R1
R2
R3
Conditionsa
Time (h)
Isolated yield
of E-2 (%)
1
2
3
4
5
6
7
8
9
10
H
H
H
H
H
H
Me
Me
Et
Ph (1a)
Ph (1a)
Ph (1b)
Ph (1b)
Ph (1c)
Ph (1c)
Ph (1d)
Ph (1d)
Ph (1e)
Ph (1e)
A
B
A
B
A
B
A
B
A
B
2.0
2.0
3.0
3.0
2.0
66 (2a)
64 (2a)
62 (2b)
70 (2b)
78 (2c)
85 (2c)
66 (2d)
74 (2d)
70 (2e)
75 (2e)
Et
Ph
Ph
Me
Me
Me
Me
3.0
n-C4H9
n-C4H9
Ph
15.0
14.0
12.0
16.0
Ph
a
Conditions A. The reaction was carried out using 0.3 mmol of 1, 0.45 mmol of
Selectfluor, 3.5 mL of commercial MeCN. Conditions B. The reaction was carried out
using 0.2 mmol of 1, 0.3 mmol of Selectfluor, 2.25 mL of anhydrous MeCN (refluxed
over CaH2) and 7.0 equiv of H2O in the atmosphere of N2.
Table 2
Fluorohydroxylation of 3-phenylbuta-1,2-dienyl diphenyl phosphine oxide (1a) with
Selectfluora
O
P
O
Ph P
O
Ph P
HO
Ph
Cl
Ph
Ph
Ph
+
N
N
solvent
temp, time
+
2BF4-
Ph
+
Ph
+
Ph
Table 4
F
F
F
1a
E-2a
E-3a
Screening of reaction conditions for the reaction of 3-phenylpropa-1,2-dienyl
Selectfluor
(1.5 equiv)
diphenyl phosphine oxide (1f) with Selectfluora
O
P
O
P
HO
Ph
Ph
Ph
Ph
Ph
solvent
Entry
MeCN/H2O
Temp
(ꢀC)
Time
(h)
NMR yield of E-2a
and E-3a (%)b
Ratio of
+
Selectfluor
1.5 equiv
E-2a/E-3ac
80 °C, time
Ph
F
1f
1
2
3
4
5
6
7
8
10/1
5/1
3/1
80
80
80
80
60
40
80
80
2.0
1.5
4.0
51.0
6.0
10.0
2.0
80
85
83
57
78
81
71 (66)
66 (64)
92/8
91/9
92/8
95/5
E-2f
Entry
Solvent
MeCN
Time (h)
NMR yield
0/1
of E-2f (%)b
10/1
10/1
1/0d
1/0e
91/9
1
23.5
24.0
11.0
11.5
13.0
54.5
20.0
24.0
33.0
58
63
68
60
40
32
88 (62)
55
69
90/10
>99/1
>99/1
2
MeCN/H2O¼20/1
MeCN/H2O¼10/1
MeCN/H2O¼10/1
MeCN/H2O¼5/1
DMF/H2O¼10/1
MeNO2/H2O¼10/1
MeNO2/H2O¼10/1
MeNO2/H2O¼10/1
3
2.0
4c
5
a
The reaction was carried out using 0.2 mmol of 1a, 0.3 mmol of Selectfuor, 2.3
mL of solvent.
6
b
NMR yield based on 1a using CH2Br2 as the internal standard.
The ratio of E-2a/E-3a was determined by 1H NMR analysis of the crude product.
Commercial MeCN was used without prior treatment.
7
c
8d
9e
d
e
Anhydrous MeCN was used together with 7 equiv H2O.
a
The reaction was carried out using 0.2 mmol of 1f, 0.3 mmol of Selectfluor, 2.2
mL of solvent.
b
NMR yield based on 1f using CH2Br2 as the internal standard.
Using 3.0 equiv of Selectfluor.
Using 1.2 equiv of Selectfluor.
The reaction was conducted at 60 ꢀC.
c
Having established the optimized fluorohydroxylation condi-
d
e
tions A (entry 7, Table 1) and conditions B (entry 8, Table 1),
attention was paid to study the scope and the limitation of the
present method. For 3,3-disubstituted 1,2-allenylic diphenyl
phosphine oxides, the yields ranged from 62 to 86% (entries 1–6,
Table 3); for fully substituted substrates, the reaction could also
proceed smoothly (entries 7–10, Table 3). In addition, it was
observed that if the phenyl at the 3-position was replaced with
a vinyl or ethyl group, the yield was rather low. Thus, the exis-
tence of an aryl group at 3-position in the starting materials is
necessary.
When 3-phenyl-1,2-propadienyl diphenyl phosphine oxide 1f
was subjected to the above conditions, the NMR yield of fluo-
rohydroxylation product E-2f was only 58%. Any other adjust-
ments referring to the ratio of MeCN/H2O had no obvious
influence even with 3.0 equiv of Selectfluor (entries 1–5, Table 4),
which prompted us to screen other solvents. Surprisingly, when
MeNO2 was used in place of MeCN, the fluorohydroxylation re-
action was remarkably improved to form the expected product
E-2f in 88% NMR yield (62% isolated) (entry 7, Table 4). In
Figure 1. ORTEP representation of E-2f.

G. He et al. / Tetrahedron 65 (2009) 8035–8042
8037
Table 6
addition, the transformation is less efficient with a less amount of
Selectfluor or at lower temperature (entries 8–9, Table 4). The
regio- and stereochemical issue was further confirmed by X-ray
diffraction study of E-2f (Fig. 1).15
Fluorohydroxylation of 3-(4-methoxyphenyl)-1,2-propadienyl diphenyl phosphine
oxide 1o with different amount of Selectfluora
MeO
MeO
F
O
Next, the scope for the differently substituted aryl group at the
3-position was explored. By comparing the results listed in entries
4–6 of Table 5, it was concluded that the steric effect of the sub-
stituents on the aryl group is not serious. When there is a strong
electron-withdrawing substituent on the benzene ring, such as
nitro group, the transformation was complete requiring 2.5 equiv of
Selectfluor producing E-2g in only 33% yield (entry 2, Table 5). In
addition to H, both C4H9 and phenyl group may be introduced to
the 1-position of the starting 3-aryl-1,2-allenyl phosphine oxides
(entries 8–9, Table 5).
Ph
Ph
P
MeNO2/H2O = 10/1
80 °C, time
O
P
Selectfluor
+
+
O
P
Ph
Ph
OH
Ph
Ph
OH
F
F
E-2o
OMe
1o
E-4o
Entry
Selectfluor
(equiv)
Time
(h)
NMR yield of
Ratio of
E-2o and E-4o (%)b
E-2o/E-4oc
1
2
1.5
2.5
3.0
0.9
3.5
7.0
5.0
8.0
8.0
8.0
38
41
43
65/35
29/71
8/92
97/3
0/100
3
4d
5
69 (45)e
25 (14)e
Table 5
a
The reaction was carried out using 0.3 mmol of 1o, Selectfluor (0.9–3.5 equiv),
Fluorohydroxylation of 3-aryl substituted 1,2-propadienyl diphenyl phosphine ox-
ides 1 with Selectfluora
3.0 mL of MeNO2, and 0.3 mL of H2O.
b
E-2o and E-4o can not be separated by flash column chromatography.
O
P
The ratio of E-2o/E-4o was determined by 1H NMR analysis after purification of
O
P
c
HO
Ph
Ph
Ar
Ph
Ph
Ar
the crude product by flash column chromatography on silica gel.
MeNO2/H2O = 10/1
80 °C, time
d
+
Selectfluor
1.5 equiv
The reaction was carried out at rt.
Isolated yields.
e
R1
F
R1
1
E-2
MeO
MeO
F
MeNO2/H2O = 10/1
Entry
R1
Ar
Time (h)
Isolated yield
of E-2 (%)
+
Selectfluor
2.2 equiv
O
P
(1)
O
P
80 °C, 8.0 h, 20%
Ph
Ph
OH
Ph
Ph
OH
1
H
H
H
H
H
H
H
C6H5 (1f)
4-NO2C6H4 (1g)
20.0
28.0
10.0
12.0
24.0
33.0
25.0
24.0
12.5
62 (2f)
33 (2g)
72 (2h)
56 (2i)
50 (2j)
56 (2k)
63 (2l)
59 (2m)
67 (2n)
2b
3
F
E-2o
F
E-4o
4-FC6H4 (1h)
4-ClC6H4 (1i)
3-ClC6H4 (1j)
2-ClC6H4 (1k)
4-MeC6H4 (1l)
C6H5 (1m)
4
,d
5c
6
7e
,d
8c
n-C4H9
C6H5
9d
C6H5 (1n)
a
The reaction was carried out using 0.3 mmol of 1f–n, 0.45 mmol of Selectfluor,
3.0 mL of MeNO2, and 0.3 mL of H2O.
b
2.5 equiv of Selectfluor were used.
2.0 equiv of Selectfluor were used.
The pure product was obtained by means of recrystallization after chromato-
c
d
graphy on silica gel (see Supplementary data for detailed information).
e
The reaction temperature was 40 ꢀC.
For 3-(4-methoxyphenyl)propa-1,2-dienyl diphenyl phosphine
oxide 1o, the reaction afforded not only the normal product E-2o
but also the double fluorinated E-4o under the optimized condi-
tions B (entry 1, Table 6) and it is difficult to separate these two
products by flash column chromatography on silica gel. After trial
and error, we observed that by employing 0.9 equiv of Selectfluor
at rt the reaction afforded E-2o highly selectively with an E-2o/
E-4o ratio as high as 97:3 (entry 4, Table 6); in addition, E-4o can
also be obtained as the only product by using 3.5 equiv of Selec-
fluor (entry 5, Table 6). Furthermore, the transformation from E-2o
to E-4o can also be realized when employing 2.2 equiv Selectfluor
(Eq. 1). The position of the fluorine atom in the methoxy-
substituted phenyl ring was also confirmed by X-ray diffraction
study (Fig. 2).16
Figure 2. ORTEP representation of E-4o.
O
P
O
P
R2
R3
HO
R2
R3
R2
R3
O
+
O
Ph
Ph
R2
R3
Ph
P
Ph
Ph
P
Ph
Ph
H2O:
Ph
+
On the basis of previous results,17 a plausible mechanism was
proposed: firstly, the fluorinonium intermediate 3 is afforded by
the interaction of the relatively electron-rich carbon-carbon
double bond in allene 1 with Fþ. Subsequently, a five-membered
cyclic intermediate 4 is formed via neighboring group paticipa-
tion of the oxygen atom of the diphenyl phosphine oxide func-
tionality. Finally, water molecule attacks the positively charged
phosphorous atom to cleave the P–O bond, forming the final
product E-2 (Scheme 1).
F
R1
F
R1
R1
R1
F
3
1
E-2
4
Scheme 1. The proposed mechanism.
3. Conclusions
In conclusion, we have developed a method for the synthesis of
3-aryl-2-fluoro-3-hydroxy-1(E)-alkenyl diphenyl phosphine oxides

8038
G. He et al. / Tetrahedron 65 (2009) 8035–8042
with high regio- and stereoselectivity from the readily available
3-aryl-1,2-allenyl phosphine oxides and Selectfluor. The stereo-
selectivity is controlled by the neighboring group participation of
the diphenyl phosphine oxide functionality as observed in our
laboratory.17 Further studies are underway in our laboratory.
CH2Cl2 and 10 mL of Et2O) afforded 1d (1.4010 g, 45%) as a colorless
liquid; 1H NMR (300 MHz, CDCl3)
7.76–7.63 (m, 4H), 7.52–7.10 (m,
d
11H), 2.48–2.32 (m, 2H), 1.83 (d, J¼6.6 Hz, 3H), 1.63–1.48 (m, 2H),
1.42–1.24 (m, 2H), 0.85 (t, J¼7.4 Hz, 3H); 31P NMR (121.5 MHz,
CDCl3)
201 (100); IR
d
30.9; MS (EI, 70 eV) m/z (%) 387 (Mþþ1, 5), 386 (Mþ, 16),
n
(neat, cmꢁ1) 3056, 2956, 2928, 2859, 1931, 1597,
4. Experimental
1494, 1460, 1437, 1369, 1195, 1117, 1101, 1067, 1027; HRMS calcd for
C26H27OP: 386.1800. Found: 386.1808.
4.1. Starting materials
4.1.4. 1,3-Diphenylbuta-1,2-dienyl diphenyl phosphine oxide (1e)
The reaction of 2,4-diphenybut-3-yn-2-ol (1.7846 g, 8.0 mmol),
pyridine (0.78 mL, d¼0.9831 g/mL, 0.77 g, 9.7 mmol), and Ph2PCl (1.60
mL, d¼1.204 g/mL, 1.93 g, 8.7 mmol) in a mixed solvent (9 mL of
CH2Cl2 and 10 mL of Et2O) afforded 1e (1.6770 g, 51%) as a colorless
Known compounds 1c and 1f were prepared according to the
published procedure.7 New compounds 1a–1b, 1d–1e, and 1g–1o
were also prepared according to this procedure.7 Select fluor (95%)
was purchased from YouLong Chemicals in China. In other cases,
select fluor was ordered from Alfa Aesar. Due to the coupling be-
tween 13C, 31P, and 19F, the 13C NMR spectra are very complicated,
however, these spectra are provided in Supplementary data.
liquid; 1H NMR (300 MHz, CDCl3)
d 7.79–7.65 (m, 6H), 7.48–7.12 (m,
14H), 1.85 (d, J¼6.0 Hz, 3H); 31P NMR (121.5 MHz, CDCl3)
d
31.0; MS
(neat,
(EI, 70 eV) m/z (%) 407 (Mþþ1,15), 406 (Mþ, 48), 205 (100); IR
n
cmꢁ1) 3056, 2922,1924,1596,1493,1437,1357,1195,1118,1102,1067,
1027; HRMS calcd for C28H23OP: 406.1487. Found: 406.1476.
4.1.1. 3-Phenylbuta-1,2-dienyl diphenyl phosphine oxide (1a)
4.1.1.1. Typical procedure I. To an oven-dried three-necked round-
bottom flask were subsequently added 2-phenylbut-3-yn-2-ol
(1.4643 g, 10 mmol), pyridine (0.96 mL, d¼0.9831 g/mL, 0.94 g, 11.9
mmol), and 10 mL of Et2O. After the mixture was cooled to 0 ꢀC with
an ice-salt bath, a solution of diphenylphosphinous chloride (2.00
mL, d¼1.204 g/mL, 2.41 g, 10.9 mmol) in 11 mL of CH2Cl2 was added
dropwise at 0 ꢀC with stirring within 1 h. After being kept for 1 h at
this temperature, the reaction mixture was allowed to warm up
naturally to room temperature and stirred at this temperature for 7
h. The solution was then poured into a flask containing smashed ice
and the aqueous layer was then extracted with 30ꢂ3 mL of CH2Cl2.
The combined organic layer was washed with 20 mL of brine and
dried over anhydrous Na2SO4. After evaporation of the solvent,
chromatography on silica gel (eluent: dichloromethane/ethyl
acetate¼10:1 to 5:1) of the crude product afforded 1a (2.0732 g,
63%) as a white solid: mp 79.5–80.5 ꢀC (Et2O/CH2Cl2); 1H NMR (300
4.1.5. 3-(4-Fluorophenyl)propa-1,2-dienyl diphenyl phosphine
oxide (1h)
The reaction of 1-(4-fluorophenyl)prop-2-yn-1-ol (1.5085 g,
10.0 mmol), pyridine (0.96 mL, d¼0.9831 g/mL, 0.94 g, 11.9 mmol),
and Ph2PCl (2.00 mL, d¼1.204 g/mL, 2.41 g, 10.9 mmol) in a mixed
solvent (11 mL of CH2Cl2 and 10 mL of Et2O) afforded 1h (1.9396 g,
58%) as a white solid: mp 124.5–125.8 ꢀC (acetone/dichloro-
methane); 1H NMR (300 MHz, CDCl3)
(m, 6H), 7.14–7.06 (m, 2H), 6.99–6.90 (m, 2H), 6.36–6.21 (m, 2H);
13C NMR (75 MHz, CDCl3)
d 7.84–7.70 (m, 4H), 7.56–7.36
d
212.8 (t, J¼2.0 Hz), 162.12 (d, Jpc¼246.2
Hz), 162.10 (d, Jpc¼246.1 Hz), 132.8 (d, Jpc¼7.4 Hz), 131.97 (d, Jpc¼3.8
Hz),131.93 (d, Jpc¼2.3 Hz),131.4 (d, Jpc¼8.1 Hz),131.2 (d, Jpc¼9.4 Hz),
131.1 (d, Jpc¼9.5 Hz),128.5–128.3 (m,1C),128.3 (d, Jpc¼2.6 Hz),127.1
(dd, J1¼7.0 Hz, J2¼3.5 Hz), 115.6 (dd, J1¼22.4 Hz, J2¼1.7 Hz), 95.3 (d,
Jpc¼13.1 Hz), 89.9 (d, Jpc¼100.4 Hz); 19F NMR (282 MHz, CDCl3)
d
ꢁ113.6 (d, JPF¼2.5 Hz); 31P NMR (121.5 MHz, CDCl3)
d 23.7 (d,
MHz, CDCl3)
2H), 7.25–7.16 (m, 3H), 6.19–6.12 (m, 1H), 1.93 (dd, J1¼6.2 Hz, J2¼3.2
Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
7.81–7.69 (m, 4H), 7.54–7.35 (m, 6H), 7.32–7.25 (m,
JFP¼3.4 Hz); MS (EI, 70 eV) m/z (%) 335 (Mþþ1, 12), 334 (Mþ, 50),
201 (100); IR n
(KBr, cmꢁ1) 3078, 3051, 2979, 2954,1939,1594,1505,
d
213.0 (d, Jpc¼1.9 Hz), 133.8 (d,
1437, 1221, 1186, 1155, 1123, 1106. Anal. Calcd for C21H16FOP: C,
75.44; H, 4.82. Found: C, 75.09; H, 4.99.
Jpc¼86.5 Hz),133.7 (d, Jpc¼89.8 Hz), 131.8 (d, Jpc¼2.3 Hz),131.7, 131.3
(d, Jpc¼10.5 Hz), 128.4 (d, Jpc¼1.4 Hz), 128.2 (d, Jpc¼1.4 Hz), 127.4,
125.7 (d, Jpc¼2.2 Hz), 103.1 (d, Jpc¼13.9 Hz), 87.6 (d, Jpc¼103.3 Hz),
4.1.6. 3-(4-Chlorophenyl)propa-1,2-dienyl diphenyl phosphine
oxide (1i)
15.7 (d, Jpc¼6.7 Hz); 31P NMR (121.5 MHz, CDCl3)
d
25.3; MS (EI, 70
(KBr, cmꢁ1
eV) m/z (%) 331 (Mþþ1,10), 330 (Mþ, 50), 201 (100); IR
n
)
The reaction of 1-(4-chlorophenyl)prop-2-yn-1-ol (2.1640 g, 13
mmol), pyridine (1.25 mL, d¼0.9831 g/mL, 1.23 g, 15.6 mmol), and
Ph2PCl (2.60 mL, d¼1.204 g/mL, 3.13 g, 14.2 mmol) in a mixed sol-
vent (14 mL of CH2Cl2 and 13 mL of Et2O) afforded 1i (2.3597 g, 52%)
as a white solid: mp 159.3–160.0 ꢀC (Et2O/CH2Cl2); 1H NMR (300
3055, 2924, 1936, 1595, 1494, 1437, 1347, 1198, 1119, 1103, 1068.
Anal. Calcd for C22H19OP: C, 79.98; H, 5.80. Found: C, 79.89; H, 5.88.
The following compounds were prepared according to Typical
procedure I.
MHz, CDCl3)
d 7.84–7.70 (m, 4H), 7.57–7.37 (m, 6H), 7.26–7.20 (m,
4.1.2. 3-Phenylpenta-1,2-dienyl diphenyl phosphine oxide (1b)
The reaction of 3-phenylpent-1-yn-3-ol (1.6058 g, 10 mmol),
pyridine (0.96 mL, d¼0.9831 g/mL, 0.94 g, 11.9 mmol), and Ph2PCl
(2.00 mL, d¼1.204 g/mL, 2.41 g, 10.9 mmol) in a mixed solvent (11
mL of CH2Cl2 and 10 mL of Et2O) afforded 1b (1.8842 g, 55%) as
2H), 7.06 (d, J¼8.1 Hz, 2H), 6.32 (dd, J1¼6.6 Hz, J2¼2.1 Hz, 1H), 6.25
(dd, J1¼10.5 Hz, J2¼6.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 212.9 (d,
Jpc¼1.3 Hz), 133.4 (d, Jpc¼2.1 Hz), 132.7 (d, Jpc¼8.6 Hz), 132.1
(d, Jpc¼2.7 Hz), 132.0 (d, Jpc¼2.7 Hz), 131.3 (d, Jpc¼10.3 Hz), 131.2 (d,
Jpc¼9.9 Hz), 130.6 (d, Jpc¼113.8 Hz), 130.5 (d, Jpc¼111.5 Hz), 128.9
(d, Jpc¼1.4 Hz),128.43 (d, Jpc¼12.5 Hz),128.40 (d, Jpc¼12.5 Hz), 128.1
(d, Jpc¼2.2 Hz), 95.4 (d, Jpc¼13.1 Hz), 90.1 (d, Jpc¼100.7 Hz); 31P NMR
a yellow liquid; 1H NMR (300 MHz, CDCl3)
d 7.80–7.67 (m, 4H),
7.54–7.34 (m, 6H), 7.34–7.16 (m, 5H), 6.23 (q, J¼3.6 Hz, 1H), 2.39–
2.13 (m, 2H), 0.93 (d, J¼7.4 Hz, 3H); 31P NMR (121.5 MHz, CDCl3)
(121.5 MHz, CDCl3)
3), 352 (Mþ 37Cl), 13), 351 (Mþ
201 (100); IR n
(KBr, cmꢁ1) 3057, 2983, 2952, 1940, 1488, 1436, 1414,
d
23.7; MS (EI, 70 eV) m/z (%) 353 (Mþ
(
37Cl)þ1,
d
25.4; MS (EI, 70 eV) m/z (%) 345 (Mþþ1, 3), 344 (Mþ, 18), 201
(
(
35Cl)þ1, 10), 350 (Mþ
(
35Cl), 36),
(100); IR
n
(neat, cmꢁ1) 3056, 2968, 2933, 2875, 1935, 1596, 1494,
1449, 1437, 1357, 1309, 1229, 1199, 1120, 1104, 1071; HRMS calcd for
C23H21OP: 344.1330. Found: 344.1335.
1186, 1121, 1105, 1091, 1012. Anal. Calcd for C21H16ClOP: C, 71.90; H,
4.60. Found: C, 71.90; H, 4.60.
4.1.3. 2-Phenylocta-2,3-dien-4-yl diphenyl phosphine oxide (1d)
The reaction of 2-phenyloct-3-yn-2-ol (1.6205 g, 8 mmol), pyr-
idine (0.78 mL, d¼0.9831 g/mL, 0.77 g, 9.7 mmol), and Ph2PCl (1.60
mL, d¼1.204 g/mL, 1.93 g, 8.7 mmol) in a mixed solvent (9 mL of
4.1.7. 3-(3-Chlorophenyl)propa-1,2-dienyl diphenyl phosphine
oxide (1j)
The reaction of 1-(3-chlorophenyl)prop-2-yn-1-ol (1.3371 g, 8.0
mmol), pyridine (0.75 mL, d¼0.9831 g/mL, 0.74 g, 9.3 mmol), and

G. He et al. / Tetrahedron 65 (2009) 8035–8042
8039
Ph2PCl (1.60 mL, d¼1.204 g/mL, 1.93 g, 8.7 mmol) in a mixed solvent
(9 mL of CH2Cl2 and 8 mL of Et2O) afforded 1j (1.9008 g, 68%) as
a white solid: mp 83.7–85.0 ꢀC (Et2O); 1H NMR (300 MHz, CDCl3)
4.1.11. 1,3-Diphenylpropa-1,2-dienyl diphenyl phosphine oxide (1n)
The reaction of 1,3-diphenylprop-2-yn-1-ol (2.0776 g, 10
mmol), pyridine (0.96 mL, d¼0.9831 g/mL, 0.94 g, 11.9 mmol), and
Ph2PCl (2.00 mL, d¼1.204 g/mL, 2.41 g, 10.9 mmol) in a mixed
solvent (12 mL of CH2Cl2 and 10 mL of Et2O) for 13 h afforded 1n
(2.1243 g, 54%) as a white solid: mp 152.6–153.1 ꢀC (n-hexane/
d
7.83–7.71 (m, 4H), 7.56–7.38 (m, 6H), 7.23–7.13 (m, 2H), 7.11–6.96
(m, 2H), 6.34 (dd, J1¼6.6 Hz, J2¼2.1 Hz, 1H), 6.23 (dd, J1¼10.8 Hz,
J2¼6.6 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d
212.8 (d, Jpc¼1.4 Hz),
134.4 (d, Jpc¼1.5 Hz), 133.0 (d, Jpc¼41.9 Hz), 132.9 (d, Jpc¼43.7 Hz),
132.1 (d, Jpc¼3.0 Hz),132.0 (d, Jpc¼1.7 Hz),131.2 (d, Jpc¼9.5 Hz),131.1
(d, Jpc¼9.6 Hz), 129.8, 128.5, 128.3, 127.7 (d, Jpc¼1.2 Hz), 126.7 (d,
Jpc¼2.1 Hz), 125.0 (d, Jpc¼2.1 Hz), 95.3 (d, Jpc¼13.4 Hz), 90.2 (d,
dichloromethane); 1H NMR (300 MHz, CDCl3)
d 7.84–7.64 (m, 6H),
7.49–7.16 (m, 12H), 7.15–7.07 (m, 2H), 6.29 (d, J¼10.8 Hz, 1H); 31P
NMR (121.5 MHz, CDCl3)
d
29.7; MS (EI, 70 eV) m/z (%) 393 (Mþþ1,
18), 392 (Mþ, 62), 201 (100); IR
n
(KBr, cmꢁ1) 3077, 3053, 3024,
Jpc¼100.4 Hz); 31P NMR (121.5 MHz, CDCl3)
d
23.8; MS (EI, 70 eV)
2970,1929,1596,1491,1457,1437,1381,1317,1192,1178,1120,1099,
1072, 1030. Anal. Calcd for C27H21OP: C, 82.64; H, 5.39. Found: C,
82.71; H, 5.37.
m/z (%) 353 (Mþ
(
37Cl)þ1, 3), 352 (Mþ
(
37Cl), 12), 351 (Mþ
(
35Cl)þ1,
9), 350 (Mþ 35Cl), 34), 201 (100); IR (KBr, cmꢁ1) 3055, 2943, 1941,
( n
1593,1569,1475,1437,1370,1262,1189,1162,1118,1080. Anal. Calcd
for C21H16ClOP: C, 71.90; H, 4.60. Found: C, 71.95; H, 4.64.
4.1.12. 3-(4-Methoxyphenyl)propa-1,2-dienyl diphenyl phosphine
oxide (1o)
4.1.8. 3-(2-Chlorophenyl)propa-1,2-dienyl diphenyl phosphine
oxide (1k)
The reaction of 1-(4-methoxylphenyl)prop-2-yn-1-ol (1.6253 g,
10 mmol), pyridine (0.96 mL, d¼0.9831 g/mL, 0.94 g, 11.9 mmol),
and Ph2PCl (2.00 mL, d¼1.204 g/mL, 2.41 g, 10.9 mmol) in a mixed
solvent (11 mL of CH2Cl2 and 10 mL of Et2O) afforded 1o (0.6880 g,
The reaction of 1-(2-chlorophenyl)prop-2-yn-1-ol (2.1653 g, 13
mmol), pyridine (1.25 mL, d¼0.9831 g/mL, 1.23 g, 15.6 mmol), and
Ph2PCl (2.60 mL, d¼1.204 g/mL, 3.13 g, 14.2 mmol) in a mixed sol-
vent (14 mL of CH2Cl2 and 13 mL of Et2O) afforded 1k (2.1188 g, 46%)
as a white solid: mp 83.5–84.5 ꢀC (Et2O/ethyl acetate); 1H NMR
20%) as a yellow liquid; 1H NMR (300 MHz, CDCl3)
d
7.83–7.72 (m,
4H), 7.54–7.38 (m, 6H), 7.10–7.05 (m, 2H), 6.84–6.78 (m, 2H), 6.31–
6.21 (m, 2H), 3.79 (s, 3H); 13C NMR (75 MHz, CDCl3)
213.2 (d,
d
(300 MHz, CDCl3)
d
7.84–7.71 (m, 4H), 7.57–7.36 (m, 6H), 7.32–7.20
Jpc¼1.3 Hz), 159.2 (d, Jpc¼1.5 Hz), 132.4 (d, Jpc¼106.1 Hz), 132.2 (d,
Jpc¼106.1 Hz), 131.91 (d, Jpc¼3.2 Hz), 131.88 (d, Jpc¼1.6 Hz), 131.3 (d,
Jpc¼9.7 Hz), 131.2 (d, Jpc¼9.7 Hz), 128.4, 128.3, 128.2 (d, Jpc¼2.4 Hz),
123.2 (d, Jpc¼7.8 Hz), 114.2 (d, Jpc¼1.4 Hz), 95.8 (d, Jpc¼13.1 Hz), 89.6
(m, 2H), 7.19–7.08 (m, 2H), 6.73 (dd, J1¼11.0 Hz, J2¼6.8 Hz, 1H), 6.33
(dd, J1¼6.6 Hz, J2¼1.8 Hz, 1H); 31P NMR (121.5 MHz, CDCl3)
d 23.9;
MS (EI, 70 eV) m/z (%) 353 (Mþ
(
37Cl)þ1, 2), 352 (Mþ
(
n
37Cl), 9), 351
(KBr, cmꢁ1
(Mþ
(
35Cl)þ1, 8), 350 (Mþ
(
35Cl), 30), 201 (100); IR
)
(d, Jpc¼102.6 Hz), 55.2; 31P NMR (121.5 MHz, CDCl3)
d 23.9; MS (EI,
3064, 3020, 3005, 2923, 1941, 1590, 1568, 1476, 1438, 1367, 1277,
1186, 1156, 1120, 1109, 1047, 1035. Anal. Calcd for C21H16ClOP: C,
71.90; H, 4.60. Found: C, 71.94; H, 4.45.
70 eV) m/z (%) 347 (Mþþ1, 18), 346 (Mþ, 70), 201 (100); IR
n (neat,
cmꢁ1) 3056, 2956, 2935, 2836, 1934, 1606, 1511, 1463, 1437, 1376,
1295, 1251, 1174, 1120, 1103, 1029; HRMS calcd for C22H19O2P:
346.1123. Found: 346.1133.
4.1.9. 3-(4-Methylphenyl)propa-1,2-dienyl diphenyl phosphine
oxide (1l)
4.1.13. 3-(4-Nitrophenyl)propa-1,2-dienyl diphenyl phosphine
oxide (1g)
The reaction of 1-(4-methylphenyl)prop-2-yn-1-ol (1.3563 g, 9.29
mmol), pyridine (0.90 mL, d¼0.9831 g/mL, 0.88 g, 11.2 mmol), and
Ph2PCl (1.90 mL, d¼1.204 g/mL, 2.29 g,10.4 mmol) in a mixed solvent
(11 mL of CH2Cl2 and 10 mL of Et2O) afforded 1l (1.3399 g, 44%) as
a white solid: mp 129.8–130.8 ꢀC (Et2O/ethyl acetate); 1H NMR (300
To an oven-dried three-necked round-bottom flask was added
1-(4-nitrophenyl)prop-2-yn-1-ol (0.3549 g, 2.0 mmol) and pyridine
(0.20 mL, d¼0.9831 g/mL, 0.20 g, 2.5 mmol), and 2.0 mL of Et2O.
After the mixture was cooled to ꢁ40 ꢀC, a solution of diphenyl-
phosphinous chloride (0.40 mL, d¼1.204 g/mL, 0.48 g, 2.2 mmol) in
2.5 mL of CH2Cl2 was added dropwise at this temperature with
stirring within 20 min. After the reaction mixture was stirred for
additional 11 h at ꢁ40 ꢀC, the resulting solution was then poured
into a flask containing smashed ice and the aqueous layer was
extracted with 20ꢂ3 mL of CH2Cl2. The combined organic layer was
washed with 10 mL of brine and dried over anhydrous Na2SO4.
After evaporation of the solvent, chromatography on silica gel (el-
uent: dichloromethane/ethyl acetate¼10/1) of the crude product
afforded 1g (0.4980 g, 69%) as a white solid: mp 155.2–156.3 ꢀC
MHz, CDCl3)
d
7.83–7.71 (m, 4H), 7.54–7.35 (m, 6H), 7.07 (d, J¼8.4 Hz,
2H), 7.03 (d, J¼8.7 Hz, 2H), 6.32–6.20 (m, 2H), 2.30 (s, 3H); 31P NMR
(121.5 MHz, CDCl3)
d
24.0; MS (EI, 70 eV) m/z (%) 331 (Mþþ1, 15), 330
(Mþ, 61), 201 (100); IR
n
(KBr, cmꢁ1) 3052, 2949, 1939, 1511, 1483,
1437, 1367, 1220, 1210, 1187, 1169, 1121, 1102, 1070, 1018. Anal. Calcd
for C22H19OP: C, 79.98; H, 5.80. Found: C, 80.02; H, 5.82.
4.1.10. 1-Phenylhepta-1,2-dien-3-yl diphenyl phosphine oxide (1m)
The reaction of 1-phenylhept-2-yn-1-ol (1.8828 g, 10 mmol),
pyridine (0.96 mL, d¼0.9831 g/mL, 0.94 g, 11.9 mmol), and Ph2PCl
(2.00 mL, d¼1.204 g/mL, 2.41 g, 10.9 mmol) in a mixed solvent (11
mL of CH2Cl2 and 10 mL of Et2O) afforded 1m (2.3002 g, 62%) as
a white solid: mp 78.6–79.6 ꢀC (n-hexane/ethyl acetate); 1H NMR
(Et2O/dichloromethane); 1H NMR (300 MHz, CDCl3)
2H), 7.85–7.69 (m, 4H), 7.59–7.37 (m, 6H), 7.31–7.21 (m, 2H), 6.47–
d 8.16–8.06 (m,
6.31 (m, 2H); 31P NMR (121.5 MHz, CDCl3)
d 23.4; MS (EI, 70 eV) m/z
(300 MHz, CDCl3)
d
7.82–7.65 (m, 4H), 7.54–7.14 (m, 9H), 7.12–7.04
(%) 362 (Mþþ1, 7), 334 (Mþ, 25), 201 (100); IR
n
(KBr, cmꢁ1) 3058,
2922, 1934, 1593, 1511, 1489, 1434, 1338, 1226, 1182, 1123, 1105.
Anal. Calcd for C21H16NO3P: C, 69.80; H, 4.46; N, 3.88. Found: C,
69.91; H, 4.46; N, 3.87.
(m, 2H), 6.12 (dt, J1¼11.1 Hz, J2¼3.2 Hz, 1H), 2.53–2.28 (m, 2H),
1.63–1.47 (m, 2H), 1.44–1.27 (m, 2H), 0.83 (t, J¼7.2 Hz, 3H); 13C
NMR (75 MHz, CDCl3)
d
209.1 (d, Jpc¼6.9 Hz), 132.5 (d, Jpc¼4.0 Hz),
131.77 (d, Jpc¼2.7 Hz), 131.76 (d, Jpc¼101.3 Hz), 131.66 (d, Jpc¼2.9
Hz), 131.5 (d, Jpc¼13.9 Hz), 131.4 (d, Jpc¼103.3 Hz), 131.3 (d, Jpc¼14.0
Hz), 128.5 (d, Jpc¼1.2 Hz), 128.2 (d, Jpc¼7.8 Hz), 128.0 (d, Jpc¼6.7
Hz), 127.3 (d, Jpc¼1.7 Hz), 126.5 (d, Jpc¼2.3 Hz), 102.9 (d, Jpc¼97.5
Hz), 97.2 (d, Jpc¼13.5 Hz), 30.4 (d, Jpc¼5.0 Hz), 27.7 (d, Jpc¼6.2 Hz),
4.2. Reaction of 3-aryl-1,2-allenyl phosphine oxides 1a–1e
with Selectfluor
4.2.1. 2-Fluoro-3-hydroxy-3-phenyl-1(E)-butenyl diphenyl
phosphine oxide (E-2a)
22.2, 13.7; 31P NMR (121.5 MHz, CDCl3)
d
29.7; MS (EI, 70 eV) m/z
(%) 373 (Mþþ1, 4), 372 (Mþ, 16), 201 (100); IR
n
(KBr, cmꢁ1) 3057,
2957, 2929, 2858, 1932, 1597, 1497, 1458, 1437, 1195, 1118, 1101,
1070, 1025. Anal. Calcd for C25H25OP: C, 80.62; H, 6.77. Found: C,
80.63; H, 6.75.
4.2.1.1. Typical procedure II (conditions A). To a solution of 1a (66.9
mg, 0.2 mmol) in 2.3 mL of MeCN was added Selectfluor (106.3 mg,
0.3 mmol) at room temperature. Then the resulting mixture was

8040
G. He et al. / Tetrahedron 65 (2009) 8035–8042
stirred at 80 ꢀC. After complete consumption of the starting ma-
terial as monitored by TLC (eluent: petroleum ether/ethyl
acetate¼2:1), the mixture was quenched with 5 mL of H2O,
extracted with 20ꢂ3 mL of diethyl ether, washed with 5 mL of
brine, and dried over anhydrous Na2SO4. Filtration, evaporation,
and flash chromatography on silica gel (petroleum ether/ethyl
acetate¼5:2) afforded E-2a (48.9 mg, 66%) as a white solid: mp
102.3–103.2 ꢀC (n-hexane/ethyl acetate); 1H NMR (300 MHz, CDCl3)
JFP¼43.7 Hz); MS (EI, 70 eV) m/z (%) 381 (Mþþ1, 0.2), 380 (Mþ, 0.3),
351 (100); IR
n
(neat, cmꢁ1) 3164, 3059, 2970, 2937, 2878, 1630,
1600, 1492, 1438, 1173, 1122, 1087, 1069; HRMS calcd for
C23H22FO2P: 380.1341. Found: 380.1349.
4.2.3.2. Conditions B. The reaction of 1b (69.1 mg, 0.2 mmol) and
Selectfluor (111.7 mg, 0.3 mmol, 95%) in anhydrous MeCN (2.25 mL)
and H2O (26.4 mg,1.4 mmol) at 80 ꢀC for 3 h afforded E-2b (53.8 mg,
70%) as a colorless liquid.
d
7.79–7.68 (m, 2H), 7.60–7.44 (m, 9H), 7.44–7.35 (m, 2H), 7.35–7.21
(m, 3H), 5.69 (dd, J1¼28.1 Hz, J2¼12.2 Hz, 1H), 1.79 (d, J¼3.3 Hz, 3H);
19F NMR (282 MHz, CDCl3)
d
ꢁ62.8 (d, JPF¼41.7 Hz); 31P NMR (121.5
4.2.4. 2-Fluoro-3-hydroxy-3,3-diphenyl-1(E)-propenyl diphenyl
phosphine oxide (E-2c)
MHz, CDCl3)
d
25.9 (d, JFP¼42.3 Hz); MS (EI, 70 eV) m/z (%) 367
(Mþþ1, 4), 366 (Mþ, 15), 351 (100); IR
n
(KBr, cmꢁ1) 3168, 3059,
2989, 2937, 1630, 1600, 1493, 1438, 1370, 1311, 1296, 1213, 1175,
1122, 1086, 1063, 1028. Anal. Calcd for C22H20FO2P: C, 72.12; H, 5.50.
Found: C, 72.20; H, 5.60.
4.2.4.1. Conditions A. The reaction of 1c (77.8 mg, 0.20 mmol) and
Selectfluor (107.5 mg, 0.30 mmol) in 2.3 mL of CH3CN at 80 ꢀC for
2 h afforded E-2c (66.4 mg, 78%) as a white solid: mp 143.5–
144.0 ꢀC (n-hexane/ethyl acetate); 1H NMR (300 MHz, CDCl3)
4.2.1.2. Typical procedure III (conditions B). To a dried Schlenk tube
were added anhydrous MeCN (2.25 mL), H2O (24.5 mg, 1.4 mmol),
and 1a (66.0 mg, 0.2 mmol) subsequently under a nitrogen atmo-
sphere at room temperature. Selectfluor (111.6 mg, 0.3 mmol, 95%)
was then added to the reaction mixture at rt. Then the resulting
mixture was stirred at 80 ꢀC for 2 h. After complete consumption of
the starting material as monitored by TLC (eluent: petroleum ether/
ethyl acetate¼2:1), the mixture was quenched with 5 mL of H2O,
extracted with 20ꢂ3 mL of diethyl ether, washed with 5 mL of
brine, and dried over anhydrous Na2SO4. Filtration, evaporation,
and flash chromatography on silica gel (petroleum ether/ethyl
acetate¼5:2) afforded E-2a (47.2 mg, 64%) as a white solid.
d 7.75–7.63 (m, 5H), 7.59–7.50 (m, 2H), 7.50–7.41 (m, 4H), 7.41–
7.33 (m, 4H), 7.33–7.25 (m, 6H), 5.92 (dd, J1¼27.2 Hz, J2¼12.2 Hz,
1H); 19F NMR (282 MHz, CDCl3)
d
ꢁ56.4 (d, JPF¼38.4 Hz); 31P
NMR (121.5 MHz, CDCl3)
d
25.7 (d, JFP¼38.8 Hz); MS (EI, 70 eV)
m/z (%) 429 (Mþþ1, 32), 428 (Mþ, 100); IR
n
(KBr, cmꢁ1) 3160,
3059, 3002, 1631, 1492, 1449, 1437, 1163, 1157, 1118, 1093, 1063,
1031. Anal. Calcd for C27H22FO2P: C, 75.69; H, 5.18. Found: C,
75.70; H, 5.25.
4.2.4.2. Conditions B. The reaction of 1c (79.0 mg, 0.20 mmol) and
Selectfluor (112.5 mg, 0.30 mmol, 95%) in anhydrous MeCN (2.25
mL) and H2O (25.3 mg,1.4 mmol) at 80 ꢀC for 3 h afforded E-2c (73.3
mg, 85%) as a white solid.
4.2.2. 2-Fluoro-3-hydroxy-3-phenyl-1(E)-butenyl diphenyl
phosphine oxide (E-2a) and 2-fluoro-3-phenylbuta-1(E), 3-dienyl
diphenyl phosphine oxide (E-3a)
4.2.5. 3-Fluoro-2-hydroxy-2-phenyl-3(E)-octen-4-yl diphenyl
phosphine oxide (E-2d)
To a solution of 1a (67.8 mg, 0.2 mmol) in 2.0 mL of MeCN were
subsequently added 0.2 mL of H2O and Selectfluor (105.7 mg, 0.3
mmol) at room temperature. Then the resulting mixture was stirred
at 80 ꢀC. After complete consumption of the starting material as
monitored by TLC (eluent: Et2O/ethyl acetate¼10:1), the mixture
was quenched with 8 mL of H2O, extracted with 20ꢂ3 mL of diethyl
ether, washed with 5 mL of brine, and dried over anhydrous
Na2SO4. Filtration and evaporation afforded the crude product,
which was analyzed by 1H NMR study to show an E-2a/E-3a ratio of
92:8. Flash chromatography on silica gel (petroleum ether/ethyl
acetate¼5:2 to 1:1) afforded E-2a (45.1 mg, 60%) and E-3a (3.9 mg,
4.2.5.1. Conditions A. The reaction of 1d (115.8 mg, 0.3 mmol) and
Selectfluor (168.2 mg, purity: 95%, 0.45 mmol) in 3.5 mL of MeCN
at 80 ꢀC for 15 h afforded E-2d (83.1 mg, 66%) as a colorless liquid;
1H NMR (300 MHz, CDCl3)
d 8.06 (s, 1H), 7.73–7.63 (m, 2H),
7.62–7.54 (m, 1H), 7.54–7.44 (m, 5H), 7.41–7.32 (m, 4H), 7.32–7.24
(m, 2H), 7.24–7.17 (m, 1H), 2.08–1.88 (m, 2H), 1.76 (d, J¼4.5 Hz, 3H),
1.00–0.82 (m, 3H), 0.82–0.63 (m, 1H), 0.57 (t, J¼7.1 Hz, 3H); 19F
NMR (282 MHz, CDCl3)
d
ꢁ66.7 (d, JPF¼32.7 Hz); 31P NMR (121.5
MHz, CDCl3)
d
35.4 (d, JFP¼32.4 Hz); MS (EI, 70 eV) m/z (%) 423
(Mþþ1, 3), 422 (Mþ, 8), 407 (100); IR
n
(neat, cmꢁ1) 3146, 3059,
5.5%). E-3a: colorless liquid; 1H NMR (300 MHz, CDCl3)
d
7.82–7.69
2957, 2937, 2871, 1620, 1493, 1437, 1171, 1140, 1119, 1098, 1072,
1060, 1028; HRMS calcd for C26H28FO2P: 422.1811. Found:
422.1811.
(m, 4H), 7.47–7.32 (m, 6H), 7.29–7.21 (m, 3H), 7.21–7.11 (m, 2H), 6.18
(dd, J1¼23.1 Hz, J2¼9.9 Hz, 1H), 6.04 (d, J¼3.0 Hz, 1H), 5.68 (d, J¼1.5
Hz, 1H); 19F NMR (282 MHz, CDCl3)
d
ꢁ62.0 (d, JPF¼38.4 Hz); 31P
NMR (121.5 MHz, CDCl3)
d
18.0 (d, JFP¼38.3 Hz); MS (EI, 70 eV) m/z
4.2.5.2. Conditions B. The reaction of 1d (76.9 mg, 0.2 mmol) and
Selectfluor (112.1 mg, 0.3 mmol, 95%) in anhydrous MeCN (2.25 mL)
and H2O (25.7 mg, 1.4 mmol) at 80 ꢀC for 14 h afforded E-2d (62.1
mg, 74%) as a colorless liquid.
(%) 349 (Mþþ1, 24), 348 (Mþ, 100); IR
n
(neat, cmꢁ1) 3056, 2926,
2854, 1627, 1575, 1496, 1438, 1332,1311, 1193, 1119, 1103, 1071, 1028;
HRMS calcd for C22H18FOP: 348.1079. Found: 348.1080.
The following compounds were prepared according to Typical
Procedure II (conditions A) and Typical Procedure III (conditions B)
respectively.
4.2.6. 2-Fluoro-3-hydroxy-1,3-diphenyl-1(E)-butenyl diphenyl
phosphine oxide (E-2e)
4.2.3. 2-Fluoro-3-hydroxy-3-phenyl-1(E)-pentenyl diphenyl
phosphine oxide (E-2b)
4.2.6.1. Conditions A. The reaction of 1e (122.1 mg, 0.3 mmol) and
Selectfluor (160.1 mg, 0.45 mmol) in 3.5 mL of MeCN at 80 ꢀC for 12
h afforded E-2e (92.6 mg, 70%) as a colorless liquid; 1H NMR (300
4.2.3.1. Conditions A. The reaction of 1b (103.9 mg, 0.3 mmol) and
Selectfluor (159.4 mg, 0.45 mmol) in 3.5 mL of MeCN at 80 ꢀC for 3 h
afforded E-2b (70.9 mg, 62%) as a colorless liquid; 1H NMR (300
MHz, CDCl3) d 8.27 (s, 1H), 7.67–7.16 (m, 15H), 7.15–6.99 (m, 3H),
6.72–6.63 (m, 2H), 1.86 (d, J¼4.2 Hz, 3H); 19F NMR (282 MHz, CDCl3)
d
ꢁ61.5 (d, JPF¼20.0 Hz); 31P NMR (121.5 MHz, CDCl3)
d 32.5 (d,
MHz, CDCl3)
d
7.81–7.70 (m, 2H), 7.59–7.44 (m, 9H), 7.43–7.21 (m,
JFP¼21.1 Hz); MS (EI, 70 eV) m/z (%) 443 (Mþþ1, 3), 442 (Mþ, 7), 427
5H), 5.73 (dd, J1¼29.0 Hz, J2¼12.2 Hz, 1H), 2.29–2.13 (m, 1H), 2.08–
(100); IR n
(neat, cmꢁ1) 3145, 3059, 2987, 2937, 1614, 1493, 1437,
1.88 (m, 1H), 0.98 (t, J¼7.4 Hz, 3H); 19F NMR (282 MHz, CDCl3)
1369, 1312, 1227, 1198, 1166, 1119, 1098, 1070, 1029; HRMS calcd for
C28H24FO2P: 442.1498. Found: 442.1490.
d
ꢁ65.2 (d, JPF¼42.0 Hz); 31P NMR (121.5 MHz, CDCl3)
d 25.9 (d,

G. He et al. / Tetrahedron 65 (2009) 8035–8042
8041
4.2.6.2. Conditions B. The reaction of 1e (75.7 mg, 0.19 mmol) and
Selectfluor (104.5 mg, 0.285 mmol, 95%) in anhydrous MeCN (2.25
mL) and H2O (23.1 mg, 1.33 mmol) at 80 ꢀC for 16 h afforded E-2e
(61.6 mg, 75%) as a colorless liquid.
12 h afforded E-2i (65.0 mg, 56%) as a white solid: mp 168.4–168.6
ꢀC (n-hexane/dichloromethane); 1H NMR (300 MHz, CDCl3)
7.74–
d
7.33 (m, 12H), 7.28–7.18 (m, 2H), 6.94 (d, J¼7.8 Hz, 1H), 5.91 (dd,
J1¼18.5 Hz, J2¼7.7 Hz, 1H), 5.68 (dd, J1¼25.4 Hz, J2¼13.4 Hz, 1H); 19
F
NMR (282 MHz, CDCl3)
d
ꢁ72.8 (d, JPF¼41.5 Hz); 31P NMR (121.5
4.3. Reaction of 3-aryl-1,2-allenyl phosphine oxides (1f–1o)
and E-2o with Selectfluor
MHz, CDCl3)
d
24.3 (d, JFP¼40.8 Hz); MS (EI, 70 eV) m/z (%) 371 (Mþ
(
37Cl)ꢁOH, 3), 370 (Mþ
(
37Cl)ꢁH2O or Mþ
(
35Cl)þ1ꢁOH, 2), 369
(Mþ
(Mþ
(
(
35Cl)þ1ꢁH2O or Mþ
(
35Cl)ꢁOH or Mþ
(
37Cl)þ1ꢁHF, 12), 368
4.3.1. 2-Fluoro-3-hydroxy-3-phenyl-1(E)-propenyl diphenyl
phosphine oxide (E-2f)
37Cl)ꢁHF or Mþ
(
35Cl)ꢁH2O, 37), 367 (Mþ
(
35Cl)þ1ꢁHF, 44),
366 (Mþ
(
35Cl)ꢁHF, 100); IR
n
(KBr, cmꢁ1) 3270, 3073, 3016, 2929,
2858, 1660, 1486, 1437, 1302, 1192, 1169, 1122, 1107, 1058, 1015.
Anal. Calcd for C21H17ClFO2P: C, 65.21; H, 4.43. Found: C, 64.85; H,
4.57.
4.3.1.1. Typical procedure IV. To a solution of 1f (62.9 mg, 0.20
mmol) in 2 mL of MeNO2 was added 0.2 mL of H2O. Then Selectfluor
(105.6 mg, 0.30 mmol) was subsequently added at room temper-
ature and the resulting mixture was stirred at 80 ꢀC. After complete
consumption of the starting material as monitored by TLC (eluent:
n-hexane/ethyl acetate¼3:2), the mixture was quenched with 5 mL
of H2O, extracted with diethyl ether (20ꢂ3 mL), washed with 5 mL
of brine, and dried over anhydrous Na2SO4. Filtration, evaporation,
and flash chromatography on silica gel (dichloromethane/ethyl
acetate¼10:1 to 5:1) afforded E-2f (43.3 mg, 62%) as a white solid:
mp 179.8–180.3 ꢀC (n-hexane/acetone); 1H NMR (300 MHz, CDCl3)
4.3.5. 2-Fluoro-3-hydroxy-3-(3-chlorophenyl)-1(E)-propenyl
diphenyl phosphine oxide (E-2j)
The reaction of 1j (70.3 mg, 0.20 mmol) and Selectfluor (148.9
mg, purity: 95%, 0.40 mmol) in 2.0 mL of MeNO2 and 0.2 mL of H2O
at 80 ꢀC for 24 h afforded E-2j (38.5 mg, 50%) as a white solid: mp
172.0–172.5 ꢀC (n-hexane/dichloromethane); 1H NMR (300 MHz,
CDCl3)
d 7.78–7.67 (m, 2H), 7.67–7.39 (m, 9H), 7.38–7.32 (m, 1H),
7.27–7.18 (m, 2H), 6.89 (dd, J1¼8.4 Hz, J2¼0.9 Hz, 1H), 5.78 (dd,
d
7.82–7.67 (m, 2H), 7.67–7.37 (m, 10H), 7.37–7.23 (m, 3H), 6.75 (dd,
J1¼17.0 Hz, J2¼8.3 Hz, 1H), 5.73 (dd, J1¼25.4 Hz, J2¼13.1 Hz, 1H); 19
F
J1¼9.0 Hz, J2¼0.9 Hz, 1H), 5.73 (dd, J1¼25.8 Hz, J2¼13.2 Hz, 1H), 5.67
NMR (282 MHz, CDCl3)
d
ꢁ71.0 (d, JPF¼39.8 Hz); 31P NMR (121.5
(dd, J1¼15.0 Hz, J2¼8.7 Hz, 1H); 19F NMR (282 MHz, CDCl3)
d
ꢁ70.0
MHz, CDCl3)
d
24.7 (d, JFP¼38.2 Hz); MS (EI, 70 eV) m/z (%) 388 (Mþ
(d, JPF¼40.6 Hz); 31P NMR (121.5 MHz, CDCl3)
d
25.0 (d, JFP¼40.8
( ( n
37Cl), 2), 386 (Mþ 35Cl), 7), 202 (100); IR (KBr, cmꢁ1) 3225, 1667,
Hz); MS (EI, 70 eV) m/z (%) 353 (Mþþ1, 3), 352 (Mþ, 13), 201 (100);
1594, 1438, 1426, 1302, 1184, 1134, 1121, 1108, 1045. Anal. Calcd for
C21H17ClFO2P: C, 65.21; H, 4.43. Found: C, 65.31; H, 4.40.
IR n
(KBr, cmꢁ1) 3314, 3058, 3016, 1661, 1599, 1491, 1454, 1437, 1290,
1279, 1191, 1124, 1108, 1086, 1050, 1026. Anal. Calcd for C21H18FO2P:
C, 71.59; H, 5.15. Found: C, 71.46; H, 5.20.
The following compounds were prepared according to Typical
procedure IV.
4.3.6. 2-Fluoro-3-hydroxy-3-(2-chlorophenyl)-1(E)-propenyl
diphenyl phosphine oxide (E-2k)
The reaction of 1k (106.0 mg, 0.30 mmol) and Selectfluor
(159.0 mg, 0.45 mmol) in 3.0 mL of MeNO2 and 0.3 mL of H2O at
80 ꢀC for 33 h afforded E-2k (65.5 mg, 56%) as a white solid: mp
148.0–148.7 ꢀC (n-hexane/dichloromethane); 1H NMR (300 MHz,
4.3.2. 2-Fluoro-3-hydroxy-3-(4-nitrophenyl)-1(E)-propenyl
diphenyl phosphine oxide (E-2g)
The reaction of 1g (71.5 mg, 0.2 mmol) and Selectfluor (186.7
mg, purity: 95%, 0.5 mmol) in 2.0 mL of MeNO2 and 0.2 mL of H2O at
80 ꢀC for 28 h afforded E-2g (25.8 mg, 33%) as a white solid: mp
161.0–161.2 ꢀC (Et2O/dichloromethane); 1H NMR (300 MHz, CDCl3)
CDCl3) d 7.85–7.64 (m, 5H), 7.63–7.41 (m, 6H), 7.35–7.17 (m, 3H),
6.84 (d, J¼7.5 Hz, 1H), 6.09 (dd, J1¼13.7 Hz, J2¼7.7 Hz, 1H), 5.85
(dd, J1¼24.9 Hz, J2¼13.2 Hz, 1H); 19F NMR (282 MHz, CDCl3)
d
ꢁ69.1 (d, JPF¼40.3 Hz); 31P NMR (121.5 MHz, CDCl3)
d 25.4 (d,
d
8.18–8.08 (m, 2H), 7.78–7.47 (m, 10H), 7.46–7.35 (m, 2H), 7.14 (d,
JFP¼38.9 Hz); MS (EI, 70 eV) m/z (%) 370 (Mþ
(
37Cl)ꢁH2O or Mþ
J¼8.4 Hz, 1H), 5.99 (dd, J1¼17.9 Hz, J2¼8.3 Hz, 1H), 5.76 (dd, J1¼25.4
(
35Cl)þ1ꢁOH, 0.1), 369 (Mþ
(
35Cl)þ1ꢁH2O or Mþ
(
35Cl)ꢁOH or
Hz, J2¼13.1 Hz, 1H); 19F NMR (282 MHz, CDCl3)
d
ꢁ71.3 (d, JPF¼38.9
Mþ
(
37Cl)ꢁF, 2), 368 (Mþ
(
37Cl)ꢁHF or Mþ
(
35Cl)ꢁH2O, 10), 367
Hz); 31P NMR (121.5 MHz, CDCl3)
d
24.8 (d, JFP¼39.4 Hz); MS (EI, 70
(Mþ
(
35Cl)þ1ꢁHF, 13), 366 (Mþ
(
35Cl)ꢁHF, 34), 331 (100); IR
n (KBr,
eV) m/z (%) 398 (Mþþ1, 5), 397 (Mþ, 15), 201 (100); IR
n
(KBr, cmꢁ1
)
cmꢁ1) 3214, 1664, 1466, 1438, 1313, 1289, 1186, 1129, 1120, 1099,
1064, 1030. Anal. Calcd for C21H17ClFO2P: C, 65.21; H, 4.43. Found:
C, 64.93; H, 4.62.
3237, 2927, 2854, 1649, 1596, 1519, 1437, 1342, 1180, 1124, 1104,
1070. Anal. Calcd for C21H17FNO4P: C, 63.48; H, 4.31; N, 3.53. Found:
C, 63.37; H, 4.29; N, 3.40.
4.3.7. 2-Fluoro-3-hydroxy-3-(4-methylphenyl)-1(E)-propenyl
diphenyl phosphine oxide (E-2l)
4.3.3. 2-Fluoro-3-hydroxy-3-(4-fluorophenyl)-1(E)-propenyl
diphenyl phosphine oxide (E-2h)
The reaction of 1l (66.2 mg, 0.20 mmol) and Selectfluor (106.0
mg, 0.30 mmol) in 2.0 mL of MeNO2 and 0.2 mL of H2O at 40 ꢀC for
25 h afforded E-2l (46.4 mg, 63%) as a white solid: mp 184.0–184.6
The reaction of 1h (100.5 mg, 0.30 mmol) and Selectfluor (159.9
mg, 0.45 mmol) in 3.0 mL of MeNO2 and 0.3 mL of H2O at 80 ꢀC for 10
h afforded E-2h (80.2 mg, 72%) as a white solid: mp 127.2–127.8 ꢀC
ꢀC (acetone/dichloromethane); 1H NMR (500 MHz, CDCl3)
d 7.77–
(acetone/dichloromethane); 1H NMR (300 MHz, CDCl3)
d
7.76–7.35
7.69 (m, 2H), 7.68–7.59 (m, 2H), 7.58–7.40 (m, 6H), 7.38 (d, J¼8.0 Hz,
2H), 7.12 (d, J¼8.5 Hz, 2H), 6.63 (d, J¼9.0 Hz, 1H), 5.70 (dd, J1¼26.0
Hz, J2¼13.0 Hz,1H), 5.64 (dd, J1¼14.3 Hz, J2¼9.3 Hz,1H), 2.32 (s, 3H);
(m, 12H), 7.02–6.90 (m, 2H), 6.86 (d, J¼8.1 Hz, 1H), 5.85 (dd, J1¼17.1
Hz, J2¼8.1 Hz, 1H), 5.69 (dd, J1¼25.2 Hz, J2¼13.2 Hz, 1H); 19F NMR
(282 MHz, CDCl3)
d
ꢁ73.0 (d, JPF¼41.2 Hz), ꢁ114.4; 31P NMR (121.5
19F NMR (282 MHz, CDCl3)
d
ꢁ70.7 (d, JPF¼40.6 Hz); 31P NMR (121.5
MHz, CDCl3)
d
24.3 (d, JFP¼40.9 Hz); MS (EI, 70 eV) m/z (%) 371
MHz, CDCl3)
d
24.7 (d, JFP¼41.2 Hz); MS (EI, 70 eV) m/z (%) 367
(Mþþ1, 1), 370 (Mþ, 4), 202 (100); IR
n
(KBr, cmꢁ1) 3321, 3077, 3018,
(Mþþ1, 2), 366 (Mþ, 7), 202 (100); IR
n
(KBr, cmꢁ1) 3328, 3017, 2922,
1657, 1602, 1507, 1437, 1294, 1228, 1191, 1155, 1123, 1107, 1067. Anal.
Calcd for C21H17F2O2P: C, 68.11; H, 4.63. Found: C, 68.19; H, 4.66.
1654,1512,1437,1295,1193,1133,1122,1106,1070,1024. Anal. Calcd
for C22H20FO2P: C, 72.12; H, 5.50. Found: C, 71.72; H, 5.62.
4.3.4. 2-Fluoro-3-hydroxy-3-(4-chlorophenyl)-1(E)-propenyl
diphenyl phosphine oxide (E-2i)
4.3.8. 2-Fluoro-1-hydroxy-1-phenyl-2(E)-hept-2-en-3-yl diphenyl
phosphine oxide (E-2m)
The reaction of 1i (105.8 mg, 0.30 mmol) and Selectfluor (159.8
mg, 0.45 mmol) in 3.0 mL of MeNO2 and 0.3 mL of H2O at 80 ꢀC for
The reaction of 1m (74.9 mg, 0.20 mmol) and Selectfluor (149.6
mg, purity: 95%, 0.40 mmol) in 2.0 mL of MeNO2 and 0.2 mL of H2O

8042
G. He et al. / Tetrahedron 65 (2009) 8035–8042
at 80 ꢀC for 21 h afforded E-2m (48.1 mg, 59%) as a white solid: mp
149.3–149.7 ꢀC (n-hexane/ethyl acetate); 1H NMR (300 MHz, CDCl3)
mmol, purity: 95%) in 3.0 mL of MeNO2 and 0.3 mL of H2O at 80 ꢀC
for 10 h afforded E-4o (23.7 mg, 20%) as a solid.
d
7.80–7.67 (m, 2H), 7.66–7.48 (m, 6H), 7.48–7.39 (m, 4H), 7.36–7.22
(m, 3H), 6.00–5.84 (m, 2H), 2.15–1.82 (m, 2H), 1.06–0.84 (m, 3H),
0.84–0.67 (m, 1H), 0.56 (t, J¼6.9 Hz, 3H); 19F NMR (282 MHz, CDCl3)
Acknowledgements
d
ꢁ79.6 (d, JPF¼33.6 Hz); 31P NMR (121.5 MHz, CDCl3)
d 33.5 (d,
JFP¼32.7 Hz); MS (EI, 70 eV) m/z (%) 390 (MþꢁH2O, 46), 201 (100); IR
Financial support from the National Natural Science Foundation
of China (No. 20572093) and the Major State Basic Research De-
velopment Program (Grant No. G2009CB825300) is greatly appre-
ciated. Shengming Ma is a Qiu Shi Adjunct Professor at Zhejiang
University. We thank Rong Zeng in our research group for repro-
ducing the results presented in entries 3 and 9 in Table 3, entries 2
and 6 in Table 5.
n
(KBr, cmꢁ1) 3345, 3061, 2954, 2869, 1653, 1494, 1454, 1436, 1231,
1184,1171,1136,1119,1101,1044,1029. Anal. Calcd for C25H26FO2P: C,
73.51; H, 6.42. Found: C, 73.50; H, 6.49.
4.3.9. 2-Fluoro-3-hydroxy-1,3-diphenyl-1(E)-propenyl diphenyl
phosphine oxide (E-2n)
The reaction of 1n (78.6 mg, 0.20 mmol) and Selectfluor (105.5
mg, 0.30 mmol) in 2.0 mL of MeNO2 and 0.2 mL of H2O at 80 ꢀC for
12.5 h afforded E-2n (57.9 mg, 67%) as a white solid: mp 192.8–
194.1 ꢀC (n-hexane/dichloromethane); 1H NMR (300 MHz, CDCl3)
Supplementary data
The 1H, 13C, and 31P spectra for all the new compounds are in-
cludedinSupplementarydata. Thismaterialisavailablefreeofcharge
via the Internet. Supplementary data associated with this article can
be found in the online version, at doi:10.1016/j.tet.2009.07.009.
d
7.76–7.62 (m, 2H), 7.61–7.50 (m, 3H), 7.50–7.20 (m,10H), 7.17–6.95
(m, 3H), 6.71 (d, J¼7.5 Hz, 2H), 6.38 (d, J¼7.8 Hz, 1H), 6.08 (dd,
J1¼20.9 Hz, J2¼8.0 Hz, 1H); 19F NMR (282 MHz, CDCl3)
d
ꢁ73.3 (d,
JPF¼21.4 Hz); 31P NMR (121.5 MHz, CDCl3)
d
30.8 (d, JFP¼21.4 Hz);
MS (EI, 70 eV) m/z (%) 409 (Mþþ1ꢁHF, 12), 408 (MþꢁHF, 45), 202
(100); IR n
(KBr, cmꢁ1) 3282, 3060, 1641, 1491, 1437, 1218, 1186, 1175,
References and notes
1118, 1101, 1083, 1055. Anal. Calcd for C27H22FO2P: C, 75.69; H, 5.18.
Found: C, 75.48; H, 5.29.
1. O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308.
2. Smart, B. E. J. Fluorine Chem. 2001, 109, 3.
3. (a) Zhao, C. Q.; Han, L. B.; Tanaka, M. Organometallics 2000, 19, 4196; (b) Zapata,
A. J.; Gu, Y.; Hammond, G. B. J. Org. Chem. 2000, 65, 227; (c) Tang, W.; Zhang, X.
Chem. Rev. 2003, 103, 3029; (d) Rubin, M.; Markov, J.; Chuprakov, S.; Wink, D. J.;
Gevorgyan, V. J. Org. Chem. 2003, 68, 6251; (e) Nishimura, T.; Hirabayashi, S.;
Yasuhara, Y.; Hayashi, T. J. Am. Chem. Soc. 2006, 128, 2556; (f) Ma, S.; Guo, H.; Yu,
F. J. Org. Chem. 2006, 71, 6634; (g) Chakravarty, M.; Kumara Swamy, K. C. J. Org.
Chem. 2006, 71, 9128.
4. For some of the most recent reports on the monofluorination, see: (a) Pacheco,
M. C.; Gouverneur, V. Org. Lett. 2005, 7, 1267; (b) Carroll, L.; Pacheco, M. C.;
Garcia, L.; Gouverneur, V. Chem. Commun. 2006, 4113; (c) Shibatomi, K.; Ya-
mamoto, H. Angew. Chem., Int. Ed. 2008, 47, 5796; (d) Takeuchi, Y.; Tarui, T.;
Shibata, N. Org. Lett. 2000, 2, 639; (e) Nie, J.; Zhu, H.; Cui, H.; Hua, M.; Ma, J. Org.
Lett. 2007, 9, 3053; (f) Stavber, G.; Zupan, M.; Jereb, M.; Stavber, S. Org. Lett.
2004, 6, 4973; (g) Gustafsson, T.; Gilmour, R.; Seeberger, P. H. Chem. Commun.
2008, 3022.
4.3.10. 2-Fluoro-3-hydroxy-3-(3-fluoro-4-methoxylphenyl)-1(E)-
propenyl diphenyl phosphine oxide (E-4o)
The reaction of 1o (104.0 mg, 0.30 mmol) and Selectfluor (391.7
mg, purity: 95%, 1.05 mmol) in 3.0 mL of MeNO2 and 0.3 mL of H2O
at 80 ꢀC for 9.5 h afforded E-4o (16.8 mg, 14%) as a white solid: mp
192.5–194.2 ꢀC (n-hexane/ethyl acetate); 1H NMR (300 MHz, CDCl3)
d
7.81–7.42 (m, 10H), 7.26–7.14 (m, 2H), 6.96–6.83 (m, 1H), 6.72 (d,
J¼8.7 Hz,1H), 5.74 (dd, J1¼25.8 Hz, J2¼12.6 Hz,1H), 5.57 (dd, J1¼14.0
Hz, J2¼8.9 Hz, 1H), 3.87 (s, 3H); 19F NMR (282 MHz, CDCl3)
d
ꢁ69.9
(d, JPF¼40.3 Hz), ꢁ134.7; 31P NMR (121.5 MHz, CDCl3)
d 25.0 (d,
JFP¼40.8 Hz); MS (EI, 70 eV) m/z (%) 401 (Mþþ1, 1), 400 (Mþ, 6), 202
(100); IR
n
(KBr, cmꢁ1) 3280, 3021, 2938, 2843, 1657, 1513, 1438,
5. Zhou, C.; Ma, Z.; Gu, Z.; Fu, C.; Ma, S. J. Org. Chem. 2008, 73, 772.
6. Zhou, C.; Li, J.; Lu, B.; Fu, C.; Ma, S. Org. Lett. 2008, 10, 581.
1430, 1310, 1272, 1215, 1177, 1138, 1121, 1112, 1059, 1026. Anal. Calcd
for C22H19F2O3P: C, 66.00; H, 4.78. Found: C, 65.93; H, 4.96.
7. Santelli-Rouvier, C.; Toupet, L.; Santelli, M. J. Org. Chem. 1997, 62, 9039.
8. (a) Barton, D. H. R.; Godinho, L. S.; Hesse, R. H.; Pechet, M. M. J. Chem. Soc., Chem.
Commun. 1968, 804; (b) Schack, C. J.; Christe, K. O. Inorg. Chem. 1979, 18, 2619;
(c) Tius, M. A. Tetrahedron 1995, 51, 6605; (d) Schmutzler, R. Angew. Chem., Int.
Ed. Engl. 1968, 7, 440; (e) Rozen, S. Chem. Rev. 1996, 96, 1717.
9. (a) Umemoto, T.; Kawada, K.; Tomita, K. Tetrahedron Lett. 1986, 27, 4465;
(b) Umemoto, T.; Fukami, S.; Tomizawa, G.; Harasawa, K.; Kawada, K.; To-
mita, K. J. Am. Chem. Soc. 1990, 112, 8563; (c) Resnati, G.; DesMarteau, D. D.
J. Org. Chem. 1991, 56, 4925.
4.3.11. 2-Fluoro-3-hydroxy-3-(4-methoxyphenyl)-1(E)-propenyl
diphenyl phosphine oxide (E-2o)
To a solution of 1o (103.3 mg, 0.30 mmol) in 3.0 mL of MeNO2
was added 0.3 mL of H2O. Then Selectfluor (101.2 mg, 0.27 mmol,
purity: 95%) was subsequently added at room temperature and the
resulting mixture was stirred at rt for 42 h. The mixture was
quenched with 5 mL of H2O, extracted with diethyl ether (20ꢂ3
mL), washed with 5 mL of brine, and dried over anhydrous Na2SO4.
Filtration, evaporation, and flash chromatography on silica gel
(petroleum ether/ethyl acetate¼3:2) afforded E-2o and E-4o as
a mixture (46.8 mg, 45%, E-2o/E-4o¼97/3). E-2o: white solid, mp
162.3–164.0 ꢀC (n-hexane/dichloromethane); 1H NMR (300 MHz,
10. (a) Banks, R. E. (Air Products and Chemicals, Inc., U.S.A.). U.S. Patent 5,086,178,
1992; (b) Banks, R. E.; Lawrence, N. J.; Popplewell, A. L. Synlett 1994, 831;
(c) Banks, R. E.; Besheesh, M. K.; Mohialdin-Khaffaf, S. N.; Sharif, I. J. Chem.
´
Soc., Perkin Trans. 1 1996, 2069; (d) Nyffeler, P. T.; Duron, S. G.; Burkart, M.
D.; Vincent, S. P.; Wong, C.-H. Angew. Chem., Int. Ed. 2005, 44, 192; (e)
Singh, R. P.; Shreeve, J. M. Acc. Chem. Res. 2004, 37, 31; (f) Stavber, S.;
Zupan, M. J. Chem. Soc., Chem. Commun. 1994, 149.
11. (a) Ma, S.; Wei, Q.; Wang, H. Org. Lett. 2000, 2, 3893; (b) Ma, S.; Ren, H.;
Wei, Q. J. Am. Chem. Soc. 2003, 125, 4817.
12. (a) Li, J.; Fu, C.; Chen, G.; Chai, G.; Ma, S. Adv. Synth. Catal. 2008, 350, 1376;
(b) Fu, C.; Ma, S. Eur. J. Org. Chem. 2005, 3942.
13. He, G.; Zhou, C.; Fu, C.; Ma, S. Tetrahedron 2007, 63, 3800.
14. Chen, G.; Fu, C.; Ma, S. Tetrahedron 2006, 62, 4444.
CDCl3)
d
7.78–7.37 (m, 12H), 6.89–6.79 (m, 2H), 6.62 (dd, J1¼8.9 Hz,
J2¼0.8 Hz, 1H), 5.70 (dd, J1¼26.1 Hz, J2¼13.2 Hz, 1H), 5.66 (dd,
J1¼14.9 Hz, J2¼8.9 Hz, 1H), 3.78 (s, 3H); 19F NMR (282 MHz, CDCl3)
15. Crystal data of E-2f: C21H18FO2P, MW¼352.32, Monoclinic, space group P21/n,
d
ꢁ70.5 (d, JPF¼40.6 Hz); 31P NMR (121.5 MHz, CDCl3)
d
24.7 (d,
(KBr, cmꢁ1
Final R indices [I>2
s
(I)], R1¼0.0315, wR2¼0.0797, R indices (all data) R1¼0.
0335, wR2¼0.0816, a¼9.2910(5) Å, b¼9.8723 (5) Å, c¼19.8349 (10) Å,
a
¼90ꢀ,
JFP¼40.8 Hz); MS (EI, 70 eV) m/z (%) 382 (Mþ, 7); IR
n
)
b
¼93.2510(10)ꢀ,
g
¼90ꢀ, V¼1816.40 (16) Å3, T¼123(2) K, Z¼4, reflections col-
3275, 3022, 2837, 1656, 1606, 1508, 1437, 1299, 1249, 1179, 1168,
1122, 1105, 1063, 1033. Anal. Calcd for C22H20FO3P: C, 69.11; H, 5.27.
Found: C, 69.03; H, 5.36.
lected/unique: 20,447/3190 (Rint¼0.0219), number of observations [>2
s(I)]
2990, parameters: 226. The Cambridge database file is CCDC-707615.
16. Crystal data of E-4o: C22H19F2O3P, MW¼400.34, Monoclinic, space group C2/c,
Final R indices [I>2
s
(I)], R1¼0.0524, wR2¼0.1444, R indices (all data) R1¼0.
0641, wR2¼0.1574, a¼18.3812(3) Å, b¼10.6050 (2) Å, c¼20.9534 (4) Å,
a
¼90ꢀ,
b
¼105.9890(10)ꢀ,
g
¼90ꢀ, V¼3926.49 (12) Å3, T¼296(2) K, Z¼8, reflections
4.3.12. 2-Fluoro-3-hydroxy-3-(3-fluor-4-methoxyphenyl)-1(E)-
propenyl diphenyl phosphine oxide (E-4o)
Following Typical procedure IV, the reaction of E-2o (117.4 mg,
E-2o/E-4o¼97.5:2.5, 0.3 mmol) and Selectfluor (246.7 mg, 0.66
collected/unique: 22,661/3462 (Rint¼0.0290), number of observations [>2
s(I)]
2798, parameters: 241. The Cambridge database file is CCDC-707616.
17. (a) Guo, H.; Qian, R.; Guo, Y.; Ma, S. J. Org. Chem. 2008, 73, 7934; (b) He, G.; Guo,
H.; Qian, R.; Guo, Y.; Fu, C.; Ma, S. Tetrahedron 2009, 65, 4877.