Conjugate addition of diethyl 1-fluoro-1-phenylsulfonylmethanephosphonate to α,β-unsaturated compounds

Article abstract of DOI:10.1021/jo400297f

Diethyl 1-fluoro-1-phenylsulfonylmethanephosphonate (1) in the presence of cesium carbonate undergoes efficient 1,4-addition to Michael acceptors having terminal double bonds such as α,β-unsaturated ketones, esters, sulfones, sulfoxides, and phosphonates

Full text of DOI:10.1021/jo400297f

Note
pubs.acs.org/joc
Conjugate Addition of Diethyl 1‑Fluoro-1-
phenylsulfonylmethanephosphonate to α,β-Unsaturated
Compounds
Stanislav Opekar,† Radek Pohl,† Vaclav Eigner,‡ and Petr Beier*,†
́
†Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam
Czech Republic
́
. 2, 166 10 Prague,
‡Department of Solid State Chemistry, Institute of Chemical Technology, Technicka
́
5, 166 28, Prague, Czech Republic
S
* Supporting Information
ABSTRACT: Diethyl 1-fluoro-1-phenylsulfonylmethane-
phosphonate (1) in the presence of cesium carbonate
undergoes efficient 1,4-addition to Michael acceptors having
terminal double bonds such as α,β-unsaturated ketones, esters,
sulfones, sulfoxides, and phosphonates to yield the corre-
sponding adducts in good to excellent yields. In the presence
of sodium hydride, 1 reacts with α,β-enones to provide γ-
fluoro-γ-phenylsulfonylenol phosphates arising from 1,4-
addition followed by phosphonate to phosphate rearrange-
ment.
Scheme 1. Published HWE and Alkylation Reactions of 1
rganic phosphates are ubiquitous molecules that play
Oimportant roles in living organisms, ranging from
information storage and transfer (DNA, RNA), energy transfer
(ATP), to separation of a cell membrane from the environment
(phospholipids).1 Phosphonates, containing nonhydrolyzable
C−P bonds, can serve as mimics for natural phosphates in
terms of their function and bioactivity. Indeed, many synthetic
phosphonates display interesting biological activities.2 More-
over, it has been realized that adjunction of electronegative
elements such as fluorine atoms to the α-position of a
phosphonate enables closer phosphate mimicry.3 α-Fluorinated
phosphonates4 are often utilized as enzyme inhibitors and
metabolic probes.5 In recent years, there has been significant
progress in studying the chemistry and bioactivity of α,α-
difluoro phosphonates.6 However, the less studied α-mono-
fluoro phosphonates have second pKa’s more closely correlating
with the pKa of natural phosphates.3b,7
nucleophilic mono-, di-, and trifluoromethylations as well as
perfluoroalkylations and polyfluoroakylations.12 The reactive
species in these processes are α-fluorinated carbanions which
are, in comparison to nonfluorinated carbanions, less polar-
izable and less nucleophilic. As a consequence, unless several
electron delocalization groups which increase polarizability
(soft character) are present on an α-fluorinated carbanionic
center, the reagent behaves as a hard nucleophile. For example,
the Ruppert−Prakash reagent (TMSCF3) is known to undergo
1,2-addition to α,β-unsaturated carbonyl compounds.12a,13 The
same behavior was observed for diethyl difluoromethylphosph-
onate in the presence of LDA; however, in the presence of
lithium-coordinating HMPA or transmetalation with CeIII salts,
Diethyl 1-fluoro-1-phenylsulfonylmethanephosphonate (1),
also known as McCarthys reagent, was introduced into organic
̀
synthesis in 1987 by Koizumi8 and further developed as a
fluoromethylene synthon by McCarthy.9 Compound 1 reacts
under basic conditions with aldehydes, ketones, and α,β-
unsaturated aldehydes in the course of the Horner−Wads-
worth−Emmons reaction to provide 1-fluoro-1-phenylsulfony-
lalkenes.8−10 Furthermore, 1 has been employed as a precursor
of α-fluoro phosphonates or α-fluorosulfones. The synthetic
strategy is based on alkylation of 1 and further desulfonation or
dephosphonylation (Scheme 1).11
Introduction of (poly)fluoroalkyl groups by nucleophilic
addition to electrophiles has been extensively studied in recent
years. Many strategies and reagents were developed for efficient
Received: February 11, 2013
Published: April 12, 2013
© 2013 American Chemical Society
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Note
a
Table 1. Optimization of the 1,4-Addition of 1 to Methyl Vinyl Ketone (2a)
b
yield (%)
entry
base (equiv)
solvent
temp (°C)
time (h)
3a
4a
1
2
Cs2CO3 (2.0)
Cs2CO3 (1.0)
Cs2CO3 (0.1)
Cs2CO3 (0.1)
Cs2CO3 (0.1)
K2CO3 (0.1)
K2CO3 (0.1)
K2CO3 (1.0)
LDA (1.1)
DMF
DMF
DMF
THF
MeCN
DMF
DMF
DMF
THF
THF
rt
1.5
0.3
0.1
4.0
1.0
42
72
89
16
8
0
c
c
3
rt
95
0
4
rt
>95
95
1
5
rt
0
6
rt
>95
>95
>95
32
0
7
50
3.0
2.5
2.0
1.5
0
8
rt
2
9
−78 to 0
−20 to 10
5
10
NaH (1.1)
<1
<1
a
b
Reactions were carried out using 1 (0.20 mmol, 1.0 equiv), 2a (1.2 equiv), and base in solvent (2.5 mL). 19F NMR yield with PhCF3 as an internal
standard unless noted otherwise. Isolated yield.
c
a
Table 2. 1,4-Addition of 1 to α,β-Unsaturated Compounds 2
a
b
c
Reactions were carried out using 1 (0.30 mmol, 1.0 equiv), 2, and Cs2CO3 in MeCN (3 mL). Isolated yield unless noted otherwise. 19F NMR
d
e
yield using PhCF3 as a standard. Pure (E)-3d was isolated by silica gel chromatorgraphy in 29% yield. Different products were formed (see
discussion below).
significant 1,4-addition to α,β-unsaturated ketones was
observed.14 Similarly, lithium salts of mono- and difluoromethyl
phenyl sulfone gave exclusive 1,2-addition to 2-cyclohexenone
but showed high 1,4-/1,2-addition ratio in the presence of
HMPA.15 On the other hand, more delocalized fluoromethyl
carbanions of 1-fluorobis(phenylsulfonyl)methane15 and tet-
raethyl fluoromethylenebisphosphonate16 undergo exclusive
conjugate addition to α,β-enones and other Michael acceptors
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The Journal of Organic Chemistry
Note
without any cation-coordinating additive. The latter reagent is
relatively bulky and requires the presence of electrophiles with
unsubstituted double bonds. Additionally, α-fluoro-β-keto
esters,17 α-fluoronitroalkanes,18 and some fluorinated sulfones
of the general formula PhSO2CFR (R = NO2, CN, CO2Et)19
were shown to undergo conjugate additions to various Michael
acceptors.
Conjugate addition of the McCarthy’s reagent has not been
studied. The process would be useful for the synthesis of
functionalized monofluoromethylene-containing compounds,
which could be further utilized for various transformations
such as reductive phenylsulfanyl group removal leading to α-
fluoro phosphonates. It was also of interest to compare the
reactivity of the McCarthy’s reagent in conjugate addition with
1-fluorobis(phenylsulfonyl)methane and tetraethyl fluorome-
thylenebisphosphonate.
Cyclohexenone (2k) did not give the desired product either
with a catalytic amount or with excess cesium carbonate.
Nevertheless, complete conversion of starting 1 with excess
cesium carbonate took place and the formation of 3k′ (four
isomers) arising from conjugate addition, and HWE reaction
was established by HRMS (ESI+) and 19F NMR analyses.
Desulfonation of selected Michael adducts 3 using
magnesium in methanol20 gave α-fluorophosphonates in good
yields (Scheme 2). During the course of the desulfonation of
3c, transesterification occurred.
Scheme 2. Desulfonation of Adducts 3 to α-
Fluorophosphonates 5
Investigation of Michael addition of 1 to methyl vinyl ketone
as a model α,β-enone provided the initial focus. Application of
conditions optimized for Michael addition of tetraethyl
fluoromethylenebisphosphonate provided the required 1,4-
addition product 3a in good NMR yield; however, a long
reaction time was needed and a significant amount of the
double addition product 4a was formed (Table 1, entry 1).
When the amount of base was reduced to 10 mol %, 3a formed
with a short reaction time as a sole product and in high isolated
yield (entry 3). The reason for the reactivity difference between
1 and tetraethyl fluoromethylenebisphosphonate16 could be
explained by the steric effect (the phosphonate moiety is
bulkier than the phenylsulfonyl group). Addition of 1 to methyl
vinyl ketone provides the anionic adduct which is able to
deprotonate starting 1. In contrast, high steric crowding of both
the fluorobisphosphonate and the product of its addition
prevents efficient proton exchange and thus requires the use of
excess base. Product 3a was formed in high yields using other
solvents than DMF (entries 4 and 5). Finally, although the
reaction time was somewhat increased (compared to DMF), it
was beneficial to carry out the reaction in low-boiling
acetonitrile. Several other bases were tested and it was found
that the reaction could be performed with catalytic potassium
carbonate at elevated temperature.
Optimized reaction conditions (Table 1, entry 5) were used
in the scope and limitation study of the 1,4-addition of 1 to
various α,β-unsaturated compounds 2 (Table 2). In addition to
methyl vinyl ketone (2a), phenyl vinyl sulfone (2b) and butyl
acrylate (2c) were found to be very reactive substrates and
provided 1,4-addition adducts 3 in high yields (entries 1−3).
Ethyl propiolate (2d) reacted with 1 in the presence of catalytic
Cs2CO3, but a higher yield of 3d and shorter reaction time was
observed with a stoichiometric amount of the base. The 19F
NMR spectrum of the crude reaction mixture indicated the
formation of the product 3d in 63% NMR yield as an E/Z 1:1
mixture (entry 4). Phenyl vinyl sulfoxide (2e), methyl
methacrylate (2f), and diethyl vinylphosphonate (2g) required
the use of at least 1 equiv of the base (entries 5−7).
Compounds 3e and 3f were formed as a mixture of
diastereomers, and the dr seemed to decrease with increasing
distance between the asymmetric centers. Chalcone (2h) did
not provide the desired product 3h (entry 8); however, the use
of 3-fold excess cesium carbonate resulted in formation of new
products (see discussion below). Benzylidine malononitrile (2i)
and β-nitrostyrene (2j) were unreactive in the presence of
catalytic amounts of cesium carbonate and an excess of the base
gave a range of unidentified fluorinated products in both cases.
Reaction of 1 with chalcone (2h) was investigated in more
detail (Table 3). With catalytic Cs2CO3, no reaction took place,
but the use of an excess of the base gave a new product, enol
phosphate 7h, in 31% isolated yield (entries 1 and 2). With
LDA in THF a mixture of the HWE product 6h and product 7h
formed in low yields (entry 3). Finally, a 2-fold excess of
sodium hydride provided 7h in good yield (entry 5).
Compound 7h formed as a mixture of separable diastereomers
with moderate diastereoselectivity. The relative configuration of
7h was determined by NMR (see Figures SI-1 to SI-4,
Supporting Information, for conformational analysis) and X-ray
diffraction analysis (see CCDC 906505 and Figure SI-5,
Supporting Information) which confirmed that the major (less
polar) diasteromer of 7h has the relative configuration as anti.
The conditions optimized for the formation of 7h were
tested on other α,β-unsaturated ketones (Table 4). With
methyl vinyl ketone (2a), a mixture of the 1,4-addition product
(3a), HWE product (6a), and product 7a was formed (entry
1). Both chalcone 2h and 2l gave compound 7 in good isolated
yield (with minor HWE product 6). Ketone 2m provided only
product 7m in good yield. On the other hand, isomeric ketone
2n gave only the product of HWE reaction. This reactivity
switch could be explained by reversible formation of 1,2-
adducts. In the reaction with 2n, the 1,2-adduct contains
relatively strongly nucleophilic alkoxide which undergoes HWE
reaction. For ketones 2h−m, however, the HWE reaction is
suppressed and 1,4-addition prevails.21 The following phos-
phonate to phosphate rearrangement to 7 involves the
formation of a 6-membered ring. This process was not
described before. Related rearrangements of γ-hydroxy
phosphonates (involving a 5-membered ring) are known.22
Surprisingly, the treatment of enol phosphates 7h with
magnesium in methanol did not provide the desulfonated
product but led to the product of dephosphonylation 8h in low
yield (25%) together with some unidentified side products. On
the other hand, strongly acidic conditions affect dephosphony-
lation of 7h, giving the ketone 8h in good yield (Scheme 3).
The crude 8h showed the same dr (64:36) as the starting 7h;
however, the dr of 8h increased to 90:10 upon isolation using
column chromatography. In contrast, Hu and co-workers
reported that the addition of fluoromethyl phenyl sulfone to
chalcone provided a mixture of 1,2/1,4-addition products in
42:58 ratio.15a
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Note
a
Table 3. Reaction of 1 with Chalcone (2h)
b
c
d
entry
1
1 (equiv)
base (equiv)
solvent
temp (°C)
time (h)
yield (%) of 6h
yield (%) of 7h
dr of 7h
1.0
1.0
1.0
1.0
2.0
Cs2CO3 (0.1)
Cs2CO3 (3.0)
LDA (1.1)
MeCN
MeCN
THF
rt
6
24
2
0
3
0
31
32
40
72
N/A
e
2
rt
66:33
64:36
62:37
3
4
5
−78 to 0
−60 to rt
0 to rt
21
6
NaH (1.1)
THF
1
NaH (2.0)
THF
1
7
64:36
a
b
c
Reactions were carried out using 1, 2h (0.20 mmol, 1 equiv), and the base in solvent (2 mL). 19F NMR yield using PhCF3 as an standard. Isolated
d
e
yield. Determined by 19F NMR of the crude product mixture. The same conditions as in Table 2, entry 8.
a
Table 4. Formation of Enol Phosphates 7 by the Addition of 1 to Unsaturated Ketones (2)
b
b
c
d
entry
2
R1
R2
yield (%) of 3
yield (%) of 6
yield (%) of 7
dr of 7
b
1
2
3
4
5
2a
2h
2l
H
Me
Ph
Ph
Ph
Me
30
0
22
7
18
Ph
72
68
68
64:36
58:42
71:29
p-Tol
Me
Ph
0
12
0
2m
2n
0
e
0
34, 70
0
a
b
Reactions were carried out using 1 (2 equiv), 2 (0.20 mmol, 1 equiv), and NaH (2 equiv) in THF (3 mL). 19F NMR yield using PhCF3 as a
c
d
e
standard. Isolated yield unless noted otherwise. Determined by 19F NMR of the crude product mixture. Using 1 (0.4 mmol, 1 equiv), 2n (4
equiv), and NaH (1.2 equiv) in THF (3 mL) at −70 to 0 °C for 1 h. E/Z ratio of 6n was 62:38.
3a. Prepared from Cs2CO3 (10 mg, 0.03 mmol), 1 (93.1 mg, 0.3
mmol) and 2a (26 mg, 0.36 mmol) in 1 h at rt giving 3a (112 mg,
95%) as a colorless liquid: Rf 0.30 (hexane−EtOAc, 1:1); H NMR
Scheme 3. Formation of γ-Fluoro Ketone 8h by
Dephosphonylation of 7h
1
(400 MHz, CDCl3) δ 1.26 (t, 3H, J = 7.1 Hz), 1.30 (t, 3H, J = 7.1 Hz),
2.14 (s, 3H), 2.37−2.65 (m, 2H), 2.78−3.04 (m, 2H), 4.09−4.26 (m,
4H), 7.53−7.59 (m, 2H), 7.65−7.72 (m, 1H), 7.92−7.97 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 16.2 (d, 3JCP = 4.3 Hz), 16.3 (d, 3JCP = 4.3
Hz), 25.4 (dd, 2JCF = 19.6 Hz, 2JCP = 2.2 Hz), 29.8, 36.7 (dd, 3JCF = 5.4
3
2
2
Hz, JCP = 2.6 Hz), 64.7 (d, JCP = 7.1 Hz), 64.9 (d, JCP = 6.8 Hz),
1
1
106.9 (dd, JCF = 228.6 Hz, JCP = 164.7 Hz), 128.7, 130.7, 134.7,
135.3, 205.7; 19F NMR (376 MHz, CDCl3) δ −164.5 (ddd, 2JFP = 80.5
Hz, 3JFH = 23.4, 16.7 Hz); 31P NMR (162 MHz, CDCl3) δ 8.8 (d, 2JPF
= 80.5 Hz); HRMS (ESI) calcd for C15H23FO6PS [M + H]+ 381.0932,
found 381.0931.
In summary, efficient conjugated addition of 1 to Michael
acceptors was accomplished using catalytic or equimolar
amounts of cesium carbonate. The adducts can be desulfonated
using magnesium in methanol to yield α-fluoro phosphonates.
Reaction of 1 with chalcones and related ketones in the
presence of sodium hydride resulted in formation of
unexpected γ-fluoro-γ-phenylsulfonylenol phosphates which
can be hydrolyzed to γ-fluoro-γ-phenylsulfonyl ketones.
3b. Prepared from Cs2CO3 (10 mg, 0.03 mmol), 1 (93 mg, 0.3
mmol), and 2b (40 mg, 0.30 mmol) in 1 h at rt giving 3b (139 mg,
1
95%) as a colorless liquid: Rf 0.22 (hexane−EtOAc, 1:1); H NMR
(400 MHz, CDCl3) δ 1.23 (t, 3H, J = 7.1 Hz), 1.27 (t, 3H, J = 7.1 Hz),
2.54−2.68 (m, 2H), 3.39−3.48 (m, 1H), 3.61−3.72 (m, 1H), 4.06−
4.23 (m, 4H), 7.52−7.59 (m, 4H), 7.64−7.73 (m, 2H), 7.86−7.90 (m,
4H); 13C NMR (100 MHz, CDCl3) δ 16.1 (d, 3JCP = 5.6 Hz), 16.2 (d,
3JCP = 5.6 Hz), 25.4 (dd, 2JCF = 20.5 Hz, 2JCP = 2.2 Hz), 50.1 (dd, 3JCF
EXPERIMENTAL SECTION
Compounds 2h, 2l, and 2n were prepared according to literature
procedure.23 HRMS (ESI) analyses were recorded using an ion trap
MS analyzer.
■
3
2
2
= 6.0 Hz, JCP = 2.5 Hz), 65.0 (d, JCP = 7.1 Hz), 65.2 (d, JCP = 6.8
Hz), 105.3 (dd, 1JCF = 230.7 Hz, 1JCP = 164.3 Hz), 128.0, 128.8, 129.4,
3
130.7 (d, JCF = 1.2 Hz), 133.9, 134.6, 135.0, 138.3; 19F NMR (376
2
3
MHz, CDCl3) δ −164.4 (ddd, JFP = 78.8 Hz, JFH = 18.9, 18.9 Hz);
31P NMR (162 MHz, CDCl3) δ 7.8 (d, 2JPF = 78.8 Hz); HRMS (ESI)
calcd for C19H24FNaO7PS2 [M + Na]+ 501.0577, found 501.0577.
3c. Prepared from Cs2CO3 (10 mg, 0.03 mmol), 1 (93 mg, 0.3
mmol), and 2c (46 mg, 0.36 mmol) in 5 h at rt giving 3c (124 mg,
General Procedure for the Synthesis of Compounds 3.
Cs2CO3 (0.03−0.90 mmol, 0.1−3.0 equiv) was placed in a Schlenk
flask, and MeCN (3 mL) and 1 (93.1 mg, 0.3 mmol, 1.0 equiv) were
added followed by addition of 2 (0.30−0.36 mmol, 1.0−1.2 equiv).
The reaction mixture was stirred at rt, followed by addition of
saturated NH4Cl (15 mL), extraction with Et2O (3 × 15 mL), drying,
and removal of solvents under reduced pressure. Purification by silica
gel column chromatography using hexane/EtOAc as eluent provided
compounds 3.
1
94%) as a colorless liquid: Rf 0.52 (hexane−EtOAc, 1:1); H NMR
(400 MHz, CDCl3) δ 0.93 (t, 3H, J = 7.4 Hz), 1.30 (t, 3H, J = 7.0 Hz),
1.33 (t, 3H, J = 7.1 Hz), 1.33−1.42 (m, 2H), 1.55−1.64 (m, 2H),
2.50−2.66 (m, 2H), 2.67−2.74 (m, 1H), 2.80−2.90 (m, 1H), 4.07 (t,
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Note
3H, J = 6.7 Hz), 4.15−4.30 (m, 4H), 7.56−7.61 (m, 2H), 7.69−7.75
(minor), 175.6 (major), 175.9 (minor); 19F NMR (376 MHz, CDCl3)
2
3
(m, 1H), 7.97−8.01 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 13.6,
δ −167.5 (ddd, JFP = 81.7 Hz, JFH = 20.9, 20.9 Hz, minor), −167.9
3
2 3
16.2 (d, 3JCP = 4.4 Hz), 16.3 (d, JCP = 4.4 Hz), 19.0, 26.8 (dd, 2JCF
=
(ddd, JFP = 81.0 Hz, JFH = 30.8, 12.8 Hz, major); 31P NMR (162
MHz, CDCl3) δ 8.5 (d, 2JPF = 81.8 Hz, minor), 8.9 (d, 2JPF = 81.0 Hz,
major); HRMS (ESI) calcd for C16H24FNaO7PS [M + Na]+ 433.0857,
found 433.0855.
19.6 Hz, 2JCP = 2.0 Hz), 28.0 (dd, 3JCF = 6.6 Hz, 3JCP = 2.7 Hz), 30.5,
64.6, 64.7 (d, 2JCP = 7.0 Hz), 64.9 (d, 2JCP = 6.8 Hz), 106.6 (dd, 1JCF
=
1
3
229.4 Hz, JCP = 164.9 Hz), 128.7, 130.8 (d, JCF = 1.2 Hz), 134.7,
135.3, 171.9; 19F NMR (376 MHz, CDCl3) δ −165.5 (ddd, 2JFP = 80.1
Hz, 3JFH = 22.3, 16.8 Hz); 31P NMR (162 MHz, CDCl3) δ 8.7 (d, 2JPF
= 80.5 Hz); HRMS (ESI) calcd for C18H28FNaO7PS [M + Na]+
461.1170, found 461.1169.
3g. Prepared from Cs2CO3 (100 mg, 0.30 mmol), 1 (93 mg, 0.3
mmol), and 2g (49 mg, 0.30 mmol) in 25 h at rt giving 3g (98 mg,
1
69%) as a colorless liquid: Rf 0.18 (EtOAc); H NMR (400 MHz,
CDCl3) δ 1.30 (t, 3H, J = 7.1 Hz), 1.32 (t, 6H, J = 7.1 Hz), 1.33 (t,
3H, J = 7.1 Hz), 2.05−2.16 (m, 1H), 2.23−2.37 (m, 1H), 2.45−2.63
(m, 2H), 4.05−4.15 (m, 4H), 4.16−4.30 (m, 4H), 7.56−7.62 (m, 2H),
7.70−7.75 (m, 1H), 7.97−8.01 (m, 2H); 13C NMR (100 MHz,
3d. Prepared from Cs2CO3 (100 mg, 0.30 mmol), 1 (93 mg, 0.3
mmol), and 2d (35 mg, 0.36 mmol) in 4 h at rt giving 3d (63% 19F
NMR yield). (E)-3d (36 mg, 29%) a colorless liquid: Rf = 0.50
(hexane-EtOAc, 1:1); 1H NMR (400 MHz, CDCl3) δ 1.28 (t, 3H, J =
7.1 Hz), 1.36 (t, 3H, J = 7.1 Hz), 1.37 (t, 3H, J = 7.1 Hz), 4.15−4.23
CDCl3) δ 16.2 (d, 3JCP = 3.7 Hz), 16.3 (d, 3JCP = 3.9 Hz), 16.4 (d, 3JCP
3
= 6.2 Hz), 16.4 (d, JCP = 6.2 Hz), 19.5 (ddd, 1JCP = 142.7 Hz, 3JCF
=
6.0 Hz, 3JCP = 2.4 Hz), 25.3 (ddd, 2JCF = 20.1 Hz, 2JCP = 2.0, 2.0 Hz),
61.7 (d, 2JCP = 1.8 Hz), 61.8 (d, 2JCP = 1.8 Hz), 64.7 (d, 2JCP = 7.0 Hz),
65.0 (d, 2JCP = 6.7 Hz), 106.4 (ddd, 1JCF = 229.9 Hz, 1JCP = 164.9 Hz,
4
(m, 2H), 4.24−4.40 (m, 4H), 5.97 (dd, 1H, J = 15.7 Hz, JFH = 4.1
Hz), 7.15 (ddd, 1H, 3JFH = 24.3 Hz, J = 15.7 Hz, 3JPH = 3.1 Hz), 7.53−
7.59 (m, 2H), 7.68−7.74 (m, 1H), 7.89−7.93 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 14.1, 16.2, 16.3, 61.1, 65.6 (d, JCP = 7.2 Hz),
3JCP = 18.9 Hz), 128.7, 130.8 (d, JCF = 1.2 Hz), 134.7, 135.1; 19F
2
3
65.7 (d, 2JC2P = 6.9 Hz), 106.0 (dd, 1JCF = 238.8 Hz, 1JCP = 165.1 Hz),
NMR (376 MHz, CDCl3) δ −165.0 (ddd, 2JFP = 80.4 Hz, 3JFH = 19.8,
19.5 Hz); 31P NMR (162 MHz, CDCl3) δ 8.5 (d, 2JPF = 80.4 Hz), 29.4
2
125.6 (dd, JCF = 10.5 Hz, JCP = 7.8 Hz), 128.1, 130.1, 133.5, 133.6,
134.5, 163.5; 19F NMR (376 MHz, CDCl3) δ −168.5 (dd, 2JFP = 74.2
(d, JPF = 3.6 Hz); HRMS (ESI) calcd for C17H30FO8P2S [M + H]+
4
3
2
Hz, JFH = 24.3 Hz); 31P NMR (162 MHz, CDCl3) δ 5.2 (d, JPF
=
475.1115, found 475.1113.
74.2 Hz); HRMS (ESI) calcd for C16H23FO7PS [M + H]+ 409.0881,
found 409.0880.
General Procedure for the Synthesis of Compounds 5. Mg
turnings (48 mg, 2 mmol, 10 equiv) were placed in a Schlenk flask
followed by addition of MeOH (1.5 mL) and a solution of 3 (0.2
mmol, 1.0 equiv) in MeOH (0.3 mL). The reaction mixture was
stirred at rt, followed by addition of 1 M HCl (10 mL) and extraction
into Et2O (3 × 15 mL). The combined organic phase was washed with
brine (10 mL) and dried, and solvent was removed under reduced
pressure. Purification by silica gel column chromatography using
hexane/EtOAc as eluent gave products 5.
3e. Prepared from Cs2CO3 (100 mg, 0.30 mmol), 1 (93 mg, 0.3
mmol), and 2e (46 mg, 0.30 mmol) in 3 h at rt giving a 1:1 mixture of
diastereomers of 3e (78 mg, 56%) as a colorless liquid: Rf 0.48
1
(EtOAc); H NMR (400 MHz, CDCl3) δ 1.26 (t, 6H, J = 7.2 Hz),
1.28 (t, 3H, J = 7.3 Hz), 1.31 (t, 3H, J = 7.1 Hz), 2.17−2.41 (m, 2H),
2
3
2.59−2.81 (m, 2H), 2.99 (ddd, 1H, JHH = 16.5 Hz, JHH = 13.5, 4.8
2
3
Hz), 3.17 (ddd, 1H, JHH = 16.5 Hz, JHH = 13.5, 4.7 Hz), 3.34 (ddd,
2
3
2
1H, JHH = 16.6 Hz, JHH = 13.6, 4.6 Hz), 3.52 (ddd, 1H, JHH = 16.1
5a. Prepared from 3a (76 mg, 0.2 mmol) in 1 h at rt giving 5a (32
mg, 66%) as a colorless liquid: Rf 0.30 (hexane−EtOAc, 1:2); 1H
NMR (400 MHz, CDCl3) δ 1.33 (t, 6H, J = 7.1 Hz), 2.07−2.28 (m,
2H), 2.14 (s, 3H), 2.59−2.78 (m, 2H), 4.15 (q, 2H, J = 7.1 Hz), 4.19
3
Hz, JHH = 13.5, 4.4 Hz), 4.07−4.28 (m, 8H), 7.48−7.61 (m, 14H),
7.68−7.73 (m, 2H), 7.85−7.93 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 16.1 (d, 3JCP = 3.3 Hz), 16.2 (d, 3JCP = 3.1 Hz), 16.2 (d, 3JCP
= 2.4 Hz), 16.3 (d, 3JCP = 3.6 Hz), 23.9 (dd, 2JCF = 20.4 Hz, 2JCP = 2.4
Hz), 23.9 (dd, 2JCF = 20.0 Hz, 2JCP = 2.3 Hz), 49.0 (dd, 3JCF = 7.0 Hz,
2
2
(q, 2H, J = 7.1 Hz), 4.73 (dddd, 1H, JFH = 46.6 Hz, JPH = 9.5 Hz,
3JHH = 4.2, 3.2 Hz); 13C NMR (100 MHz, CDCl3) δ 16.3 (d, 3JCP = 2.9
Hz), 16.4 (d, 3JCP = 3.0 Hz), 24.1 (dd, 2JCF = 20.3 Hz, 2JCP = 1.5 Hz),
29.9, 38.2 (dd, 3JCF = 11.1 Hz, 3JCP = 4.2 Hz), 62.8 (d, 2JCP = 6.7 Hz),
3JCP = 3.7 Hz), 49.1 (dd, 3JCF = 6.6 Hz, 3JCP = 2.5 Hz), 64.9 (d, 2JCP
7.1 Hz), 65.0 (d, 2JCP = 7.1 Hz), 65.0 (d, 2JCP = 7.2 Hz), 65.1 (d, 2JCP
=
=
6.5 Hz), 106.2 (dd, 1JCF = 230.1 Hz, 1JCP = 164.5 Hz), 106.3 (dd, 1JCF
= 229.7 Hz, 1JCP = 163.8 Hz), 124.0, 124.0, 128.8, 128.8, 129.2, 129.2,
130.7, 130.7, 131.0, 131.0, 134.8, 134.8, 134.8, 134.9, 142.4, 142.6; 19F
NMR (376 MHz, CDCl3) δ −164.1 (ddd, 2JFP = 79.3 Hz, 3JFH = 23.6,
2
1
1
63.2 (d, JCP = 6.9 Hz), 87.7 (dd, JCF = 179.4 Hz, JCP = 170.9 Hz),
206.8; 19F {1H} NMR (376 MHz, CDCl3) δ −210.8 (d, JPF = 75.8
2
Hz); 31P NMR (162 MHz, CDCl3) δ 17.5 (d, 2JPF = 75.7 Hz); HRMS
(ESI) calcd for C9H18FO4P [M]+ 240.0927, found 240.0925.
16.5 Hz), −163.6 (ddd, JFP = 79.2 Hz, JFH = 23.9, 15.2 Hz); 31P
NMR (162 MHz, CDCl3) δ 8.0 (d, 2JPF = 79.3 Hz), 8.1 (d, 2JPF = 79.2
Hz); HRMS (ESI) calcd for C19H25FO6PS2 [M + H]+ 463.0809, found
463.0809.
2
3
5c. Prepared from 3c (88 mg, 0.2 mmol) in 2 h at rt giving 5c (45
mg, 87%) as a colorless liquid: Rf 0.44 (hexane−EtOAc, 1:3); 1H
NMR (400 MHz, CDCl3) δ 1.37 (t, 6H, J = 7.1 Hz), 2.16−2.34 (m,
2H), 2.49−2.66 (m, 2H), 3.70 (s, 3H), 4.20 (q, 2H, J = 7.1 Hz), 4.23
2
2
3f. Prepared from Cs2CO3 (200 mg, 0.60 mmol), 1 (93 mg, 0.3
mmol), and 2f (36 mg, 0.36 mmol) in 21 h at rt giving a 3:1 mixture of
diastereomers of 3f (59 mg, 48%) as a colorless liquid: Rf 0.34
(hexane−EtOAc, 1:1); 1H NMR (400 MHz, CDCl3) δ 1.20−1.40 (m,
9H, major), 1.20−1.40 (m, 9H, minor), 2.20−2.37 (m, 1H, major),
2.20−2.37 (m, 1H, minor), 2.80−2.96 (m, 1H, major), 2.96−3.08 (m,
1H, minor), 3.11−3.21 (m, 1H, major), 3.11−3.21 (m, 1H, minor),
3.59 (s, 3H, major), 3.69 (s, 3H, minor), 4.12−4.35 (m, 4H, major),
4.12−4.35 (m, 4H, minor), 7.55−7.64 (m, 2H, major), 7.55−7.64 (m,
2H, minor), 7.69−7.75 (m, 1H, major), 7.69−7.75 (m, 1H, minor),
7.97−8.05 (m, 2H, major), 7.97−8.05 (m, 2H, minor); 13C NMR (100
MHz, CDCl3) δ 16.2 (d, 3JCP = 2.1 Hz, major), 16.2 (d, 3JCP = 2.1 Hz,
minor), 16.3 (d, 3JCP = 2.1 Hz, major), 16.3 (d, 3JCP = 2.1 Hz, minor),
(q, 2H, J = 7.1 Hz), 4.80 (dddd, 1H, JFH = 46.8 Hz, JPH = 8.2 Hz,
3JHH = 5.6, 3.8 Hz); 13C NMR (100 MHz, CDCl3) δ 16.3 (d, 3JCP = 2.7
Hz), 16.4 (d, 3JCP = 2.7 Hz), 25.5 (d, 2JCF = 20.2 Hz), 29.1 (dd, 3JCF
=
=
3
2
2
12.7 Hz, JCP = 4.6 Hz), 51.6, 62.8 (d, JCP = 6.6 Hz), 63.2 (d, JCP
6.8 Hz), 87.5 (dd, 1JCF = 180.0 Hz, 1JCP = 171.2 Hz), 172.6; 19F {1H}
NMR (376 MHz, CDCl3) δ −211.5 (d, JPF = 75.2 Hz); 31P NMR
2
(162 MHz, CDCl3) δ 17.3 (d, 2JPF = 75.2 Hz); HRMS (ESI) calcd for
C9H18FNaO5P [M + Na]+ 279.0768, found 279.0768.
General Procedure for the Synthesis of Compounds 6 and 7.
NaH (10 mg, 0.40 mmol, 2 equiv) and THF (2 mL) were placed in a
Schlenk flask. The resulting suspension was cooled to 0 °C, and a
solution of 1 (128 mg, 0.40 mmol, 2 equiv) in THF (0.5 mL) was
added. The color of the solution became yellow, and after a few
minutes a solution of 2 (0.20 mmol, 1 equiv) in THF (0.5 mL) was
added. The reaction mixture was allowed to warm to rt, and after 1−2
h a solution of saturated NH4Cl (20 mL) was added. The product was
extracted into Et2O (3 × 20 mL) and dried, and solvent was removed
under reduced pressure. Purification by silica gel column chromatog-
raphy using hexane/EtOAc as eluent gave products 6 and 7.
2
2
18.9 (minor), 19.5 (major), 33.7 (dd, JCF = 18.2 Hz, JCP = 2.1 Hz,
minor), 34.3 (dd, 2JCF = 18.5 Hz, 2JCP = 2.1 Hz, major), 34.7 (dd, 3JCF
= 4.2 Hz, 3JCP = 2.0 Hz, major), 34.8 (dd, 3JCF = 4.2 Hz, 3JCP = 2.2 Hz,
2
minor), 51.7 (major), 51.9 (minor), 64.6 (d, JCP = 6.9 Hz, minor),
64.8 (d, 2JCP = 7.0 Hz, major), 64.8 (d, 2JCP = 6.9 Hz, minor), 64.9 (d,
1
1
2JCP = 6.8 Hz, major), 107.0 (dd, JCF = 231.3 Hz, JCP = 165.0 Hz,
1
1
major), 107.2 (dd, JCF = 231.3 Hz, JCP = 165.9 Hz, minor), 128.6
(major), 129.1 (minor), 130.8 (d, 3JCF = 1.4 Hz, major), 130.9 (d, 3JCF
= 1.3 Hz, minor), 134.6 (major), 134.9 (minor), 135.2 (major), 135.4
7h. Prepared from 2h (42 mg, 0.2 mmol) in 1 h giving 7h as a
colorless oil (74 mg, 72%). Silica gel column chromatography and
crystallization gave anti-7h (37 mg) as colorless crystals: mp 90−91 °C
4577
dx.doi.org/10.1021/jo400297f | J. Org. Chem. 2013, 78, 4573−4579

The Journal of Organic Chemistry
Note
(Et2O−pentane); Rf 0.60 (hexane−EtOAc, 1:1); 1H NMR (400 MHz,
CDCl3) δ 1.17 (td, 3H, J = 7.1 Hz, 4JPH = 1.1 Hz), 1.31 (td, 3H, J = 7.1
Hz, 4JPH = 1.1 Hz), 3.91−4.29 (m, 4H), 4.94 (ddd, 1H, 3JHF = 28.4 Hz,
C21H26FNaO6PS [M + Na]+ 479.1064, found 479.1062. minor-7m (16
1
mg), a pale yellow oil: Rf 0.48 (hexane−EtOAc, 1:1); H NMR (400
MHz, CDCl3) δ 1.21 (t, 3H, J = 7.1 Hz), 1.28 (t, 3H, J = 7.1 Hz), 1.42
(d, 3H, J = 7.0 Hz), 3.78−3.92 (m, 1H), 3.95−4.22 (m, 4H), 5.16 (dd,
2
3
3JHH = 10.1, 4.5 Hz), 5.69 (dd, 1H, JHF = 46.4 Hz, JHH = 4.5 Hz),
1H, 2JHF = 46.5 Hz, 3JHH = 3.9 Hz), 5.49 (dd, 1H, 3JHH = 9.9 Hz, 4JHP
=
3
4
5.89 (dd, 1H, JHH = 10.1 Hz, JPH = 1.9 Hz), 7.22−7.27 (m, 3H),
7.31−7.39 (m, 5H), 7.42−7.48 (m, 2H), 7.51−7.55 (m, 2H), 7.56−
7.61 (m, 1H), 7.78−7.82 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
1.5 Hz), 7.29−7.34 (m, 3H), 7.43−7.47 (m, 2H), 7.47−7.53 (m, 2H),
7.56−7.62 (m, 1H), 7.92−7.96 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 15.9 (d, 3JCP = 7.0 Hz), 16.0 (d, 3JCP = 7.0 Hz), 16.9 (d, 3JCF
= 2.2 Hz), 32.0 (dd, 2JCF = 18.7 Hz, 4JCP = 1.2 Hz), 64.5 (d, 2JCP = 6.4
3
3
2
15.9 (d, JCP = 6.9 Hz), 16.1 (d, JCP = 6.9 Hz), 42.0 (dd, JCF = 18.2
4
2
2
Hz, JCP = 1.2 Hz), 64.7 (d, JCP = 6.0 Hz), 64.8 (d, JCP = 5.9 Hz),
2
1
5
1
5
3
Hz), 64.6 (d, JCP3 = 6.5 Hz), 104.5 (dd, JCF = 223.6 Hz, JCP = 1.3
104.0 (dd, JCF = 225.2 Hz, JCP = 2.4 Hz), 113.4 (dd, JCP = 7.1 Hz,
3
3JCF = 4.7 Hz), 126.1, 127.7, 128.3, 128.5, 128.9, 129.1, 129.2, 129.3,
Hz), 113.7 (dd, JCP = 6.6 Hz, JCF = 6.6 Hz), 125.9, 128.1, 128.8,
129.1, 129.4, 134.2, 134.9, 136.7, 147.4 (d, JCP = 9.1 Hz); 19F NMR
2
134.0, 134.7 (d, 3JCF = 1.2 Hz), 136.0 (d, JCF = 0.9 Hz), 136.6, 147.4
3
(376 MHz, CDCl3) δ −183.4 (dd, 2JHF = 46.4 Hz, 3JHF = 22.8 Hz); 31
P
(d, 2JCP = 8.7 Hz); 19F NMR (376 MHz, CDCl3) δ −185.0 (dd, 2JHF
=
3
46.4 Hz, JHF = 28.4 Hz); 31P NMR (162 MHz, CDCl3) δ −5.7 (s);
HRMS (ESI) calcd for C26H28FNaO6PS [M + Na]+ 541.1221, found
541.1219. syn-7h (26 mg) as colorless oil: Rf 0.56 (hexane−EtOAc
NMR (162 MHz, CDCl3) δ −6.0 (s); HRMS (ESI) calcd for
C21H26FNaO6PS [M + Na]+ 479.1064, found 479.1063.
8h. A mixture of 7h (52 mg, 0.1 mmol) and 36% aqueous HCl (2
mL) was heated at 70 °C for 20 h. A saturated solution of NaHCO3
(10 mL) was added, and the product was extracted into Et2O (3 × 10
mL). The combined organic phase was washed with brine (10 mL)
and dried (MgSO4), and solvent was removed under reduced pressure.
Purification by silica gel column chromatography using hexane/EtOAc
gave 8h as a pale yellow liquid (28 mg, 75%). major-8h (12 mg), a pale
yellow oil: Rf 0.49 (hexane−EtOAc, 4:1); 1H NMR (400 MHz,
1
1:1); H NMR (400 MHz, CDCl3) δ 1.17−1.22 (m, 6H), 3.92−4.13
(m, 4H), 5.10 (ddd, 1H, 3JHF = 30.0 Hz, 3JHH = 9.5, 2.3 Hz), 5.34 (dd,
2
3
3
4
1H, JHF = 46.6 Hz, JHH = 2.5 Hz), 5.87 (dd, 1H, JHH = 9.5 Hz, J
PH= 1.5 Hz), 7.25−7.36 (m, 6H), 7.38−7.46 (m, 4H), 7.47−7.53 (m,
2H), 7.57−7.62 (m, 1H), 7.93−7.97 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 16.0 (d, 3JCP = 6.8 Hz), 16.0 (d, 3JCP = 6.8 Hz), 41.3 (d, 2JCF
= 17.4 Hz), 64.5 (d, 2JCP = 6.0 Hz), 64.6 (d, 2JCP = 6.0 Hz), 104.5 (d,
2
3
CDCl3) δ 3.68 (dd, 1H, JHH = 18.0 Hz, JHH = 10.2 Hz), 3.94 (dd,
1JCF = 227.3 Hz), 110.4 (dd, JCP = 7.2 Hz, JCF = 7.1 Hz), 126.1,
3
3
2
3
3
1H, JHH = 17.9 Hz, JHH = 2.9 Hz), 4.53 (dddd, 1H, JHF = 30.4 Hz,
3JHH = 10.1, 2.7, 2.0 Hz), 5.30 (dd, 1H, 2JHF = 47.6 Hz, 3JHH = 1.9 Hz),
7.20−7.31 (m, 3H), 7.34−7.38 (m, 2H), 7.41−7.46 (m, 2H), 7.51−
7.61 (m, 3H), 7.66−7.72 (m, 1H), 7.90−7.97 (m, 4H); 13C NMR
(100 MHz, CDCl3) δ 38.5 (d, 3JCF = 5.0 Hz), 39.2 (d, 2JCF = 17.6 Hz),
3
127.6, 128.1, 128.3, 128.9, 129.0, 129.2, 129.6, 134.3, 134.8 (d, JCF
=
F
1.3 Hz), 136.4, 138.7 (d, JCF = 1.9 Hz), 148.4 (d, JCP = 9.2 Hz); 19
3
2
2
3
NMR (376 MHz, CDCl3) δ −186.3 (dd, JHF = 46.5 Hz, JHF = 30.0
Hz); 31P NMR (162 MHz, CDCl3) δ −6.4 (s); HRMS (ESI) calcd for
C26H28FNaO6PS [M + Na]+ 541.1221, found 541.1219.
1
104.5 (d, JCF = 226.1 Hz), 127.7, 128.0, 128.2, 128.6, 128.9, 129.3,
7l. Prepared from 2l (44 mg, 0.2 mmol) in 1.5 h giving 7l as a pale
yellow oil (72 mg, 68%). major-7l, a colorless oil: Rf 0.55 (hexane-
129.4, 133.2, 134.6, 136.3, 136.6, 139.6, 196.2; 19F NMR (376 MHz,
CDCl3) δ −185.1 (dd, 2JHF = 47.6 Hz, 3JHF = 30.3 Hz); HRMS (ESI)
calcd for C22H19FNaO3S [M + Na]+ 405.0931, found 405.0932. minor-
8h (isolated in a mixture with major-8h 65:35, 16 mg): Rf 0.44
(hexane−EtOAc, 4:1).
1
3
EtOAc 1:1); H NMR (500 MHz, CDCl3) δ 1.17 (td, 3H, JHH = 7.0
Hz, 4JPH = 1.1 Hz), 1.32 (td, 3H, 3JHH = 7.0 Hz, 4JPH = 1.1 Hz), 2.29 (s,
3H), 3.91−4.28 (m, 4H), 4.91 (ddd, 1H, 3JHF = 28.8 Hz, 3JHH = 10.1,
2
3
4.4 Hz), 5.68 (dd, 1H, JHF = 46.4 Hz, JHH = 4.4 Hz), 5.87 (dd, 1H,
3JHH = 10.1 Hz, JHP = 1.9 Hz), 7.04−7.09 (m, 2H), 7.23−7.27 (m,
4
ASSOCIATED CONTENT
■
2H), 7.34 (m, 3H), 7.42−7.47 (m, 2H), 7.50−7.54 (m, 2H), 7.58−
7.61 (m, 1H), 7.78−7.82 (m, 2H); 13C NMR (125 MHz, CDCl3) δ
S
* Supporting Information
Conformational analysis of syn- and anti-7h. Copies of 1H, 13C,
19F, and 31P NMR spectra of newly synthesized products. This
material is available free of charge via the Internet at http://
pubs.acs.org.
15.9 (d, 3JCP = 6.9 Hz), 16.0 (d, JCP = 6.9 Hz), 21.1, 41.6 (dd, 2JCF
=
3
4
2
2
18.2 Hz, JCP = 1.3 Hz), 64.6 (d, JCP = 6.0 Hz), 64.8 (d, JCP = 6.0
Hz), 104.2 (dd, 1JCF = 224.9 Hz, 5JCP = 2.4 Hz), 113.6 (dd, 3JCP = 6.9
3
Hz, JCF = 4.6 Hz), 126.1, 128.2, 128.9, 129.1, 129.1, 129.2, 129.3,
132.9 (d, 3JCF = 1.1 Hz), 133.9, 134.7 (d, 3JCF = 1.3 Hz), 136.7, 137.3,
147.2 (d, 2JCP = 8.7 Hz); 19F NMR (470 MHz, CDCl3) δ −185.4 (dd,
2JHF = 46.4 Hz, 3JHF = 28.9 Hz); 31P NMR (203 MHz, CDCl3) δ −5.7
(s); HRMS (ESI) calcd for C27H31FO6PS [M + H]+ 533.1558, found
533.1559. minor-7l, a pale yellow oil: Rf 0.50 (hexane-EtOAc, 1:1); 1H
AUTHOR INFORMATION
Corresponding Author
*E-mail: beier@uochb.cas.cz.
■
3
4
NMR (500 MHz, CDCl3) δ 1.19 (td, 3H, JHH = 7.1 Hz, JPH = 1.1
Notes
3
4
Hz), 1.21 (td, 3H, JHH = 7.0 Hz, JPH = 1.1 Hz), 2.31 (s, 3H), 3.93−
4.16 (m, 4H), 5.05 (ddd, 1H, 3JHF = 29.5 Hz, 3JHH = 9.6, 2.6 Hz), 5.33
(dd, 1H, 2JHF = 46.6 Hz, 3JHH = 2.7 Hz), 5.84 (dd, 1H, 3JHH = 9.6 Hz,
4JHP = 1.5 Hz), 7.11−7.15 (m, 2H), 7.27−7.33 (m, 5H), 7.41−7.45
(m, 2H), 7.47−7.52 (m, 2H), 7.56−7.62 (m, 1H), 7.92−7.96 (m, 2H);
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Academy of Sciences of the
Czech Republic (RVO: 61388963) and the Grant Agency of
the Czech Republic (203/08/P310).
19F NMR (470 MHz, CDCl3) δ −185.9 (dd, JHF = 46.6 Hz, JHF
=
2
3
29.5 Hz); 31P NMR (203 MHz, CDCl3) δ −6.3 (s).
7m. Prepared from 2m (29 mg, 0.2 mmol) in 1 h giving 7m as a
pale yellow oil (62 mg, 68%). major-7m (46 mg), a pale yellow liquid:
Rf 0.71 (hexane−EtOAc, 1:1); 1H NMR (400 MHz, CDCl3) δ 1.15 (t,
3H, J = 7.1 Hz), 1.32 (t, 3H, J = 7.1 Hz), 1.41 (d, 3H, J = 6.8 Hz),
3.80−4.30 (m, 5H), 5.44 (dd, 1H, 2JHF = 47.5 Hz, 3JHH = 3.3 Hz), 5.52
(dd, 1H, 3JHH = 9.4 Hz, 4JHP = 2.0 Hz), 7.31−7.36 (m, 3H), 7.50−7.54
(m, 2H), 7.55−7.61 (m, 2H), 7.65−7.70 (m, 1H), 7.97−8.01 (m, 2H,
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CArH); 13C NMR (100 MHz, CDCl3) δ 14.1 (d, JCF = 5.3 Hz), 15.8
3
3
2
(d, JCP = 7.1 Hz), 16.0 (d, JCP = 7.0 Hz), 30.9 (d, JCF = 19.4 Hz),
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3
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2
(376 MHz, CDCl3) δ −191.3 (dd, 2JHF = 47.0 Hz, 3JHF = 27.6 Hz); 31
P
NMR (162 MHz, CDCl3) δ −5.6 (s); HRMS (ESI) calcd for
4578
dx.doi.org/10.1021/jo400297f | J. Org. Chem. 2013, 78, 4573−4579

The Journal of Organic Chemistry
Note
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