A difluorosulfide as a freon-free source of phosphonodifluoromethyl carbanion

Article abstract of DOI:10.1039/b301729j

The synthesis of difluoromethylphosphonates is becoming difficult due to environmental protective laws restricting the use of HCFCs and CFCs as starting chemicals. To circumvent this limitation, we report the preparation of a thioether as a new source of the lithiodifluoromethylphosphonate. This methodology avoiding the use of HCFCs involves a selective fluorination of sulfide followed by a thiaphilic addition of an organometallic reagent, which offers an alternative route to obtain phosphonodifluoromethyl carbanion. A contrasted reactivity, due to a medium effect, was also noted which allows addition of a wide range of electrophiles including nitroalkenes and DMF to thioethers.

Full text of DOI:10.1039/b301729j

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A difluorosulfide as a Freon-free source of
phosphonodifluoromethyl carbanion†
Arnaud Henry-dit-Quesnel,a Loic Toupet,b Jean-Claude Pommeleta and Thierry Lequeux*a
a Laboratoire de Chimie Moléculaire et Thioorganique, UMR CNRS 6507, Université de Caen,
ENSICaen 6 Bd du Maréchal Juin, F 14050 Caen, France.
E-mail: Thierry.Lequeux@ismra.fr; Fax: 33 23145 2877; Tel: 33 23145 2854
b Groupe Matière Condensée et Matériaux, UMR CNRS 6626, Université de Rennes 1,
Bâtiment 11A, F 35042 Rennes Cedex, France
Received 13th February 2003, Accepted 27th May 2003
First published as an Advance Article on the web 6th June 2003
The synthesis of difluoromethylphosphonates is becoming difficult due to environmental protective laws restricting
the use of HCFCs and CFCs as starting chemicals. To circumvent this limitation, we report the preparation of a
thioether as a new source of the lithiodifluoromethylphosphonate. This methodology avoiding the use of HCFCs
involves a selective fluorination of sulfide followed by a thiaphilic addition of an organometallic reagent, which offers
an alternative route to obtain phosphonodifluoromethyl carbanion. A contrasted reactivity, due to a medium effect,
was also noted which allows addition of a wide range of electrophiles including nitroalkenes and DMF to thioethers.
ations and the syntheses of functionalised or heterosubstituted
Introduction
difluoromethylenephosphonates appear much more difficult.12
It is well established that phosphate analogues bearing the
difluoromethylenephosphonate moiety present a better bio-
activity than the corresponding methylenephosphonates. This
To date, the building blocks or the carbanionic and the free
radical approaches remain the best routes to prepare various
aliphatic difluorophosphonates. To maintain these promising
strategies, we investigated the synthesis of sulfides as building-
property has been widely applied in the preparation of import-
ant enzyme inhibitors and new drugs.1 The synthesis of such
blocks, which do not depend on CFCs or HCFCs as starting
complex molecules can be realised by direct introduction or
materials, and explored their uses as precursors for both
construction of the difluoromethylenephosphonate function,1,2
phosphonodifluoromethyl radical and carbanion.
or by using building blocks already fluorophosphorylated.3 In
the majority of cases, the most popular starting materials are
the organolithium and the organozinc reagents. The former
was originally used by Kondo,4 from the diethyl difluoro-
methylphosphonate 1,5 and the latter from the diethyl bromo-
difluoromethylphosphonate 26 in the Burton’s group.7 Follow-
ing the discovery of these reagents several other nucleophilic
organometallic reagents have been reported. They have been
prepared by transmetalation reaction, reduction of alkyl
halides,1,3,7 or nucleophilic displacement of halogen atom,8
from 1–3. Later gem-difluoroalkenes as free radical acceptors
and halogenated or chalcogenated phosphonates as free radical
precursors were used to trap phosphonyl radicals,2 or form
phosphonodifluoromethyl radicals,9 as alternative routes to the
carbanionic reactions. However, all these methodologies were
developed from CFC or HCFC as starting chemicals (Scheme
1), and are now problematic due to environmental protective
laws.
Results and discussion
First, the synthesis of alkylsulfanyl fluorophosphonates was
investigated through a halogen-exchange reaction using our
previous protocol for the synthesis of fluoroacetates.13 As
reported the rate of the halex reaction was strongly dependent
on the nature of the alkylsulfanyl moiety. In the present case, all
attempts to prepare arylsulfanyl difluoromethylphosphonates
were unsuccessful. Alkylsulfanyl derivatives were more
reactive and the chlorine–fluorine exchange was observed when
performed with the 3HF–NEt3complex in the presence of zinc
bromide (Scheme 2). In this way isopropylic ester 5a was
isolated in 62% overall yields from 4a,14 while the more sensitive
ethyl ester 5b was obtained in 35% yield.15
Scheme 2
In connection with our work concerning the synthesis and
the use of fluorosulfides, we explored their potential as carb-
anion precursors by heterolytic cleavage of the carbon–sulfur
bond. The cleavage of the carbon–sulfur bond is well known to
produce free radicals.16 In contrast, production of the corre-
sponding carbanion by heterolytic cleavage of the carbon–
sulfur or -selenium bond is less well studied. In general, the
selective displacement of the sulfur atom can be realised with
nucleophilic organometallic reagents if assisted by the presence
of carbanion stabilizing group (aryl, alkylsulfanyl) or with
reductive metals in the presence or absence of arene.17 Other
alternative methods consist of the nucleophilic attack upon the
corresponding sulfoxide by organomagnesium reagents.18
Scheme 1
Since the beginning of the 21st century, the Montreal
Protocol has regulated the use and the freight of CFCs, HCFCs
and halogenated derivatives,10 and compromised the future
development of these strategies. To circumvent this limitation,
the electrophilic or nucleophilic fluorination of phosphonates
represented a competitive alternative to prepare activated, benz-
ylic or propargylic difluoromethylphosphonate derivatives.11
Nevertheless, the fluorination technique presented some limit-
† In memory of Arnaud who passed away in his 25th year.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 8 6 – 2 4 9 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
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Table 1 Addition reaction with representative electrophiles
In a previous communication, we reported the free radical
reactions from methylsulfanyldifluoromethylphosphonate ester
5a.9e In this case the yields of addition products were lower than
those observed from phosphonosulfides.19 This difference was
attributed to the poor radicophilicity of difluorosulfides, which
reacted slowly with tin radical. This particular polarity of the
sulfur atom prompted us to examine its behaviour in nucleo-
philic displacements using organometallic reagents. Using
alkylmagnesium bromide (MeMgBr or iPrMgBr) no reaction
occurred even at room temperature, and sulfide 5a was
recovered quantitatively. When using the n-butyllithium at Ϫ78
ЊC, diisopropyl phosphonate 67b was obtained by acidic
hydrolysis of the crude mixture (Scheme 3). The cleavage of
the carbon–sulfur bond was regioselective, only affecting the
sulfur-difluoromethylene bond.18c The displacement was slow,
and the complete consumption of the sulfide 5a was observed
when the reaction was performed over 40 min of stirring in the
presence of slight excess of alkyllithium (1.3 eq.).
Electrophilea
Product
Yieldb
(CH3)3SiCl
PhCHO
(CH3)3Si–CF2P(O)(OiPr)2
8a
8b
69%
67%
iPrCHO
8c
8d
72%
76%
cC6H11CHO
nC8H17CHO
8e
8f
86%
69%
a Experimental runs at Ϫ78 ЊC in the presence of 1.3 eq. of electrophile.
b Isolated yield.
Scheme 3
Table 2 Syntheses of building blocks from 5a
Nevertheless, the formation of difluorophosphonoester 6 was
accompanied by a variable amount (20–30%) of butylphos-
phonate 7,20 formed by nucleophilic attack at the phosphorus
centre by the n-butyllithium.21 When the more sterically
hindered nucleophile tert-butyllithium was used, this competi-
tive nucleophilic substitution was avoided. With tert-butyl-
lithium, the sulfur displacement was faster and spontaneous
affording diisopropyl difluoromethylphosphonate 6 in 97%
yield. As previously described, 6 was accompanied by the
formation of less than 3% of tetraisopropyldifluoromethyl-
enediphosphonate (δF Ϫ122.4 ppm (t, 2JPF 87.2)).8a,22 Following
this procedure the lithiophosphonate was also trapped with
various representative electrophiles (Table 1–2, Scheme 4).
Results were compared to those observed from 1 and 2.
Electrophile
Product
Yielda
70%
9a
9b
73%
CS2–CH3I
9c
59%b
(PhS)2
(PhSe)2
I2
PhS–CF2P(O)(OiPr)2
PhSe–CF2P(O)(OiPr)2
I–CF2P(O)(OiPr)2
9d
9e
9f
49%c
50%c
70%c
a Isolated yield. b 5 equivalents of CS2 and CH3I were used. c Experi-
mental runs with 3 equivalents of electrophile.
Scheme 4
With chlorotrimethylsilane, silylated phosphonate 8a was
isolated in 69% yield and with carbonyl compounds, the corre-
sponding alcohols 8b–8f were obtained in 67–86% yields (Table
1). In all cases, no deprotonation of the methylsulfanyl group
was observed.23 The scope of the method was extended to a
wide range of electrophiles (Table 2). The addition of the carb-
anion species was not limited to aldehydes or ketones and it
reacted with esters and imines to afford β-amino and β-keto-
phosphonates in 70–73% yields. A range of building blocks
9c–9f can be obtained in fair to good yields from the methyl-
phosphonate 5a. The sulfanyl exchange can be achieved, by
using the diphenyldisulfide or diselenide as electrophiles. In this
way useful free radical precursors 9d–9e can be obtained in fair
yields.9 In addition, by reacting the anion directly with iodine,
diisopropyl iododifluoromethylphosphonate 9f was prepared in
70% yield. This was generally obtained directly from CF2I2 or
the organomagnesium and organocadmium reagents.8a,24 In the
case of the preparation of 9d–9f, excess of electrophile (3
equivalents) was required to observe a complete consumption
of the lithiophosphonate. It is noteworthy that these yields
were similar and competitive to those observed when experi-
ments are run from the difluoromethyl- and bromodifluoro-
methylphosphonates 1 or 2.4,8
Scheme 5 Reagents and conditions: (i) tBuLi inverse addition, THF,
Ϫ78 ЊC, 5 min; (ii) RCH᎐CHNO2 (3 eq.); (iii) NH4Cl; (iv) DMF (1.2
᎐
eq.); (v) HCl 1 M.
Trapping the lithiophosphonate prepared from 5a was also
attempted with electrophiles that failed to react with the
lithiated species issued from 1 (Scheme 5). First, the reaction
was performed with nitroalkenes. From aryl- and alkyl-
nitroalkenes, the conjugate addition was successful, affording
secondary difluoromethylphosphonates 10a–b. These were
isolated in 39–57% when excess of Michael acceptor (3 eq.) was
used. In addition, the anion generated from 5a reacted with
DMF. In this particular case, crystalline aldehyde hydrate 11,25
was isolated in 80% yield and identified by X-ray analysis
(Scheme 5, Fig. 1).
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 8 6 – 2 4 9 1
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nitrogen. After 5 minutes of stirring, neat 3HF–NEt3 complex
(25 mL, 152 mmol) were added dropwise. After 2 hours under
reflux, the reaction mixture was cooled down to rt and poured
into NH4Cl and extracted with Et2O–DCM (3 × 30 mL of a
2 : 1 mixture). The organic layers were washed with NaHCO3,
brine, dried over MgSO4, filtered and concentrated. The
residual oil was purified by distillation using a vigreux column
(66–72 ЊC/10Ϫ1 mbar) leading to 5a (7.2 g, 62% overall from 4a)
as a colorless oil. δH (250 MHz; CDCl3) 1.4 (12H, dd, 3JHH 6.2,
3
3
4JHP 3.3, iPr), 2.4 (3H, s, CH3S), 4.8 (2H, dsept, JHP and JHH
3
3
6.3, iPr); δC (100.6 MHz; CDCl3) 9.7 (dt, JCP 2.2, JCF 5.4,
CH3S), 23.0 (d, 3JCP 5.3, iPr), 23.6 (d, 3JCP 3.3, iPr), 74.6 (d, 2JCP
6.9, iPr), 124.8 (dt, 1JCP 223.4, 1JCF 296.7, CF2); δP (101.2 MHz;
2
CDCl3) 1.02 (t, JFP 103.5); δF (235.2 MHz; CDCl3) Ϫ89.84
(d, JFP 103.5); νmax(film)/cmϪ1 2984, 2938, 1274 (P᎐O), 1112
2
᎐
(C–O), 1012 (C–F); m/z (EI) 262 (Mϩ, 4%), 205 (21), 178 (71),
161 (15), 132 (100), 123 (27), 112 (22), 97 (40), 79 (32), 47 (19),
45 (18), 43 (38); Anal. Calcd for C8H17F2O3PS: C, 36.64; H,
6.53; Found: C, 36.43; H, 6.43%.
Fig. 1 ORTEP diagram of 11.
The difluorophosphonato anion prepared from the sulfide
5a is most surprising in view of the previously reported
unsuccessful attempts to carry out additions to DMF and
nitroalkenes.26 This was probably due to the difference of the
medium, which seems to be enough to modify the aggregates of
the lithiated anion. This avoided the use of additive (CeCl3) to
mediate its conjugate addition onto nitroalkenes, and its
addition with DMF.
In conclusion, we have reported the synthesis of methyl-
sulfanyl difluoromethylphosphonate ester 5a and showed that
it has great potential as a new source of phosphonodifluoro-
methyl carbanion by heterolytic cleavage of the carbon–sulfur
bond. This method, which avoids HCFCs and CFCs as starting
materials, ensures sustainability for well-known and useful
fluorophosphorylated building blocks for the next decade. In
addition, the resulting lithiophosphonate prepared by this way
reacted with a wide range of electrophiles without any need
for transmetallation. The complete study of it reactivity
towards alkyl halides, triflates and oxacycles are under investi-
gation in our laboratory in order to prepare analogues of
β-hydroxyphosphonates.
Typical procedure for the preparation of phosphonates (6–11)
Neat diisopropylmethylsulfanyldifluoromethyl phosphonate 5a
(300 mg, 1.15 mmol) was added dropwise to a cold solution
(Ϫ78 ЊC) of tert-butyllithium (1.15 mL, 1.49 mmol, 1.3 M in
pentane) in dry THF (10 mL). After 5 minutes of stirring at
Ϫ78 ЊC, neat electrophile (1.3 or 3 eq.) was slowly added and
the mixture was stirred for 1 h. Saturated aqueous solution of
NH4Cl (2 mL) was added and the reaction mixture was slowly
warmed to 20 ЊC and extracted with Et2O–DCM (2 : 1). The
organic layer was washed with brine, dried over magnesium
sulfate, filtered, concentrated in vacuum. Unless otherwise
stated, the crude was purified by flash chromatography or bulb-
to-bulb distillation.
Diisopropyl difluoromethylphosphonate (6)7b
By quenching the anion with NH4Cl, 247 mg of 6 (97%) were
obtained as a colorless oil. δH (250 MHz; CDCl3) 1.38 (12 H,
3
4
3
3
dd, JHH 6.4, JHP 3.1, iPr), 4.85 (2H, dsept, JHP and JHH 6.4,
iPr), 5.78 (1H, dt, 2JHP 26.8, 2JHF 48.9, HCF2); δC (100.6 MHz;
CDCl3) 22.8 (d, 3JCP 4.7, iPr), 23.1 (d, 3JCP 5.7, iPr), 72.7 (d, 2JCP
6.7, iPr), 110.9 (dt, 1JCP 214.4, 1JCF 257.9, CF2); δP (101.2 MHz;
2
Experimental
CDCl3) 4.3 (t, JFP 90.7); δF (235.2 MHz; CDCl3) Ϫ136.0 (dd,
2JFP 90.7, JFH 48.9); νmax(film)/cmϪ1 2984, 1262 (P᎐O), 1058
2
1
Unless otherwise stated, H NMR (250, 400 MHz), 13C NMR
᎐
(C–O), 1002 cmϪ1 (C–F); m/z (EI) 216 (Mϩ, 13%), 202 (16), 55
(62.9, 100.6 MHz), 19F NMR (235.2 MHz) and 31P NMR
(101.2 MHz) spectra were recorded on Bruker DPX or Avance
spectrometers relative to (CH3)4Si, CDCl3, CFCl3 and 85%
H3PO4, respectively. Chemical shifts are expressed in parts per
million (ppm) and J values in Hz. Low resolution and high
resolution mass spectra were recorded on Unicam ATI
Automass and Nermag R101H spectrometers, and JEOL 500
spectrometers, respectively. IR spectra were recorded on
Perkin-Elmer 16PC FT-IR spectrometers. Chemicals were
purchased from Aldrich or Acros and were used without
further purification.
(16), 51 (100), 42 (17).
Diisopropyl difluoro(trimethylsilyl)methylphosphonate (8a)
From 190 µL of trimethylsilyl chloride (1.49 mmol), 353 mg of
crude oil were obtained. By bulb-to-bulb distillation (50 ЊC/10Ϫ1
mbar), 226 mg of 8a (69%) were isolated as a colorless oil. δH
(250 MHz; CDCl3) 0.24 (9H, br s, (CH3)3Si), 1.34 (12H, dd,
3JHH 6.2, 4JHP 2.8, iPr), 4.83 (2H, dsept, 3JHP and 3JHH 6.2, iPr);
δC (62.9 MHz; CDCl3) Ϫ3.8 (s, (CH3)3Si), 23.7 (d, 3JCP 4.9, iPr),
3
2
1
24.2 (d, JCP 3.4, iPr), 72.8 (d, JCP 7.2, iPr), 126.2 (dt, JCP
1
2
168.0, JCF 271.2, CF2); δP (101.2 MHz; CDCl3) 11.6 (t, JFP
Diisopropyl methylsulfanyldifluoromethylphosphonate (5a)
94.1); δF (235.2 MHz; CDCl3) Ϫ131.7 (d, 2JFP 94.1); νmax(film)/
cmϪ1 3484, 2982, 2242, 1468, 1456, 1386, 1254 (P᎐O), 1106
᎐
Sulfuryl chloride (7.76 mL, 95.4 mmol) was added slowly to a
solution of diisopropyl methylsulfanylmethylphosphonate
4a (9.8 g, 43.4 mmol) in CH2Cl2 (80 mL) stirred under nitrogen
at 0 ЊC. After 2 hours of stirring, the solvent was evaporated
in vacuum. 12.8 g of diisopropyl methylsulfanyldichloromethyl-
phosphonate were obtained as a pale yellow oil and were used
in the next step without any purification. δH (250 MHz; CDCl3)
1.4 (12H, dd, 3JHH 6.2, 4JHP 2.6, iPr), 2.6 (3H, d, 4JHP 1.5, CH3S),
4.9 (2H, dsept, 3JHP and 3JHH 6.2, iPr).
(C–O), 1004 (C–F), 850, 762, 734; m/z (EI) 288.108 (Mϩ,
C10H23F2O3PSi requires 288.112), 231 (12%), 204 (33), 189 (24),
141 (100), 125 (83), 73 (41), 43 (29).
Diisopropyl 1,1-difluoro-2-hydroxy-2-phenylethylphosphonate
(8b)
From 152 µL of benzaldehyde (1.49 mmol), 397 mg of crude oil
were obtained. By flash chromatography using petroleum
ether–ethyl acetate (7 : 3), 248 mg of 8b (67%) were isolated as a
white solid (mp 94–96 ЊC/hexane–acetone (8 : 2)). δH (400 MHz;
Diisopropylmethylsulfanyldichloromethyl phosphonate (12.8
g, 43.4 mmol) was added to a suspension of freshly dried zinc
bromide (4.88 g, 21.7 mmol) in acetonitrile (80 mL) under
3
4
CDCl3) 1.31 (12H, dd, JHH 6.3, JHP 4.2, iPr), 4.05 (1H, br s,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 8 6 – 2 4 9 1
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OH), 4.82 (2H, dsept, 3JHP and 3JHH 6.3, iPr), 5.08 (1H, dd, 3JHF
(2H, dsept, 3JHH and 3JHP 6.2, iPr); δC (100.6 MHz; CDCl3) 14.1
3 3
3
20.2, JHF 5.1, CH(OH)), 7.35–7.50 (5H, m, Ph); δC (100.6
(s, CH3), 22.7 (s, CH2), 23.7 (d, JCP 5.1, iPr), 23.8 (d, JCP 5.0,
iPr), 24.2, 24.3, 25.4, 28.8, 29.3, 29.4, 31.9 (s, CH2), 71.8 (ddd,
2JCF 33.6, 2JCF 24.7, 2JCP 13.9, CH(OH)), 74.1 (d, 2JCP 7.2, iPr),
74.2 (d, 2JCP 7.1, iPr), 118.6 (dt, 1JCP 207.0, 1JCF 268.5, CF2P); δP
MHz; CDCl3) 23.5 (d, 3JCP 5.2, iPr), 23.7 (d, 3JCP 5.2, iPr), 24.1
(d, 3JCP 4.0, iPr), 24.2 (d, 3JCP 3.0, iPr), 73.7 (ddd, 2JCF 25.6, 2JCF
2
2
2
21.2, JCP 14.9, CH(OH)), 74.4 (d, JCP 7.1, iPr), 74.6 (d, JCP
1
1
1
2
2
7.4, iPr), 117.3 (ddd, JCF 271.0, JCF 266.4, JCP 206.0, CF2),
127.9, 128.2, 128.8 (s, Ph), 134.7 (t, JCF 6.2, Ph); δP (101.2
MHz; CDCl3) 8.6 (dd, JFP 99.3, JFP 105.1); δF (235.2 MHz;
(101.2 MHz; CDCl3) 6.7 (dd, JFP 101.2, JFP 105.9); δF (235.2
3
MHz; CDCl3) Ϫ118.4 (1F, ddd, 3JHF 7.1, 2JFP 101.2, 2JFF 301.3),
2
2
3
2
2
Ϫ126.7 (1F, ddd, JHF 18.8, JFP 105.9, JFF 303.6); νmax(film)/
3
2
2
CDCl3) Ϫ115.4 (1F, ddd, JHF 5.1, JFP 99.3, JFF 302.6),
Ϫ126.30 (1F, ddd, 3JHF 20.2, 2JFP 105.1, 2JFF 302.6); νmax(KBr)/
cmϪ1 3852, 3744, 2928, 2858, 2360, 1696, 1508, 1458, 1256
(P᎐O), 1000 (C–F); m/z (CI, CH ) 359.207 (MHϩ, C H F O P
᎐
4
16 34
2
4
cmϪ1 3330, 2990, 2936, 2360, 1456, 1386, 1250 (P᎐O), 1068
requires 359.2163), 161 (28%), 132 (100), 110 (24), 41 (16).
᎐
(C–O), 996 (C–F), 730, 574; m/z (EI) 322 (Mϩ, 4%), 221 (20),
174 (17), 132 (100), 110 (17), 107 (13), 77 (12); Anal. Calcd
for C14H21F2O4P: C, 52.17; H, 6.57; Found: C, 52.41; H,
6.56%.
Diisopropyl difluoro(1-hydroxycyclohexyl)methylphosphonate
(8f)
From 112 µL of cyclohexanone (1.49 mmol), 423 mg of crude
oil were obtained. By flash chromatography using petroleum
ether–ethyl acetate (8 : 2), 249 mg of 8f (69%) were isolated as a
white solid (mp 60–61 ЊC/hexane–acetone (8 : 2)) δH (250 MHz;
CDCl3) 1.36 (12H, dd, 4JHP 2.3, 3JHH 6.2, iPr), 1.46–1.87 (10H,
Diisopropyl 1,1-difluoro-2-hydroxy-3-methylbutylphosphonate
(8c)
From 135 µL of isobutyraldehyde (1.49 mmol), 443 mg of
crude oil were obtained. By bulb-to-bulb distillation (65 ЊC/
5.10Ϫ2 mmHg), 237 mg of 8c (72%) were isolated as a colorless
oil δH (400 MHz; CDCl3) 1.07 (3H, d, 3JHH 6.4, CH3), 1.10 (3H,
3
3
m, CH2), 3.17 (1H, br s, OH), 4.84 (2H, dsept, JHP and JHH
6.2, iPr); δC (100.6 MHz; CDCl3) 20.5 (s, CH2), 23.7 (d, 3JCP 5.1,
iPr), 24.1 (d, 3JCP 3.3, iPr), 25.4 (s, CH2(CH2C(OH))), 29.9 (td,
3
2
2
3
3
4
3JCF and JCP 2.8, CH2(C(OH))), 73.9 (dt, JCP 13.7, JCF 21.1,
C(OH)), 74.2 (d, 2JCP 7.5, iPr), 119.7 (dt, 1JCP 201.5, 1JCF 270.7,
CF2); δP (101.2 MHz; CDCl3) 7.2 (t, 2JFP 105.9); δF (235.2 MHz;
d, JHH 6.4, CH3), 1.37 (12H, dd, JHH 6.1, JHP 2.6, iPr), 2.12
3
3
(1H, dsept, JHH and JHH 6.4, CH), 3.30 (1H, br s, OH), 3.76
3
3
3
3
(1H, dddd, JHF 22.4, JHF 4.4, JHP and JHH 6.4, CHa(OH)),
4.85 (2H, dsept, 3JHP and 3JHH 6.4, iPr); δC (100.6 MHz; CDCl3)
17.04 (s, CH3), 18.2 (s, CH3), 23.6 (d, 3JCP 5.3, iPr), 23.7 (d, 3JCP
CDCl3) Ϫ122.5 (d, JFP 105.9); νmax(KBr)/cmϪ1 3394, 2986,
2
2942, 1448, 1388, 1376, 1252 (P᎐O), 1128, 1046, 1014 (C–F);
᎐
3
3
m/z (EI) 314 (Mϩ, 1%), 210 (20), 174 (20), 132 (100), 110 (22),
81 (18); Anal. Calcd for C13H25F2O4P: C, 49.68; H, 8.02; Found:
C, 49.64; H, 8.05%.
5.1, iPr), 24.1 (d, JCP 3.3, iPr), 24.2 (d, JCP 3.1, iPr), 28.2 (d,
3JCP 5.2, CH), 74.0 (d, 2JCP 7.3, iPr), 74.1 (d, 2JCP 7.1, iPr), 75.5
2
2
2
1
(ddd, JCF 34.3, JCF 20.9, JCP 13.1, CHa(OH)), 119.5 (dt, JCP
205.5, JCF 270.0, CF2); δP (101.2 MHz; CDCl3) 6.8 (dd, JFP
1
2
2
Diisopropyl 1,1-difluoro-2-phenyl-2-phenylaminoethylphos-
phonate (9a)
108.3, JFP 103.6); δF (235.2 MHz; CDCl3) Ϫ115.7 (1F, ddd,
3JHF 4.4, JFP 103.6, JFF 306.0), Ϫ127.2 (1F, ddd, JHF 22.4,
2
2
3
2JFP 108.3, JFF 306.0); νmax(film)/cmϪ1 3744, 3372, 2984, 2360,
2
From 270 mg of N-phenylbenzylimine (1.49 mmol), 570 mg
of crude oil were obtained. By flash chromatography using
petroleum ether–ethyl acetate (8 : 2), 319 mg of 9a (70%) were
isolated as a white solid (mp 123–125 ЊC/hexane–acetone (7 : 3))
1652, 1466, 1254 (P᎐O), 1184, 1002 (C–F); m/z (EI) 288
᎐
(Mϩ, 7%), 205 (18), 161 (72), 132 (100), 110 (16); Anal. Calcd
for C11H23F2O4P: C, 45.83; H, 8.04; Found: C, 46.03; H,
8.02%.
3
δH (250 MHz; CDCl3) 1.24 (3H, d, JHH 6.1, iPr), 1.29 (3H, d,
3JHH 6.2, iPr), 1.30 (3H, d, 3JHH 6.2, iPr), 1.35 (3H, d, 3JHH 6.2,
3
3
iPr), 4.80 (2H, dsept, JHP and JHH 6.2, iPr), 4.95 (1H, dddd,
Diisopropyl 2-cyclohexyl-1,1-difluoro-2-hydroxyethylphos-
phonate (8d)
3
3
3
3JHF 20.6, JHF and JHP and JHH 7.6, CH(NH)), 5.10 (1H, d,
3JHH 7.6, NH), 7.07–7.14 (2H, m, Ph), 6.58–6.73 (3H, m, Ph),
7.31–7.51 (5H, m, Ph); δC (100.6 MHz; CDCl3) 23.5 (d, 3JCP 5.7,
From 180 µL of cyclohexanecarboxaldehyde (1.49 mmol), 545
mg of crude oil were obtained. By bulb-to-bulb distillation (130
ЊC/7.10Ϫ2 mbar), 288 mg of 8d (76%) were isolated as a colorless
oil δH (250 MHz; CDCl3) 1.20–1.35 (5H, m, CHϩCH2), 1.36–
1.40 (12 H, m, iPr), 1.65–1.85 (6H, m, CH2), 2.91 (1H, br s,
3
3
3
iPr), 23.6 (d, JCP 5.5, iPr), 24.1 (d, JCP 4.2, iPr), 24.2 (d, JCP
5.9, iPr), 60.9 (ddd, 2JCF 25.3, 2JCF 21.2, 2JCP14.4), 74.1 (d, 2JCP
7.2, iPr), 74.2 (d, 2JCP 7.3, iPr), 118.0 (td, 1JCF 267.4, 1JCP 211.1,
CF2), 113.7, 118.3, 128.4, 128.6, 128.8, 129.2, 134.6, 145.9
(s, Ph); δP (101.2 MHz; CDCl3) 6.2 (dd, 2JFP 101.2, 2JFP 105.9);
3
3
3
3
OH), 3.75 (1H, dddd, JHF 22.2, JHF 4.9, JHP and JHH 6.0,
3
3
CH(OH)), 4.85 (2H, dsept, JHH and JHP 6.3, iPr); δC (62.9
3
2
δF (235.2 MHz; CDCl3) Ϫ111.1 (1F, ddd, JHF 7.6, JFP 101.2,
MHz; CDCl3) 23.6 (d, 3JCP 5.3, iPr), 23.7 (d, 3JCP 5.3, iPr), 24.1
2JFF 303.6), Ϫ121.85 (1F, ddd, 3JHF 20.6, 2JFP 105.9, 2JFF 303.6);
3
3
νmax(KBr)/cmϪ1 3318, 2984, 1604, 1500, 1252 (P᎐O), 1180, 1050,
(d, JCP 3.1, iPr), 24.2 (d, JCP 2.8, iPr), 25.9, 26.1, 26.3, 27.1,
30.0, 37.9 (s, chx), 73.9 (d, 2JCP 7.3, iPr), 74.00 (d, 2JCP 7.1, iPr),
74.8 (ddd, 2JCF 24.0, 2JCF 21.4, 2JCP 13.4, CH(OH)), 119.8 (ddd,
᎐
1010 (C–F), 698; m/z (EI) 397 (Mϩ, 17%), 182 (100), 104 (9), 77
(9); Anal. Calcd for C20H26F2NO3P: C, 60.45; H, 6.59. Found:
C, 60.47; H, 6.68%.
1JCF 270.3, JCF 266.8, JCP 207.7, CF2P); δP (101.2 MHz;
1
1
CDCl3) 6.8 (dd, 2JFP 107.2, 2JFP 101.4); δF (235.2 MHz; CDCl3)
3
2
2
Ϫ115.3 (1F, ddd, JHF 4.9, JFP 101.8, JFF 304.4), Ϫ123.9 (1F,
Diisopropyl 1,1-difluoro-2-oxo-2-phenylethylphosphonate (9b)
ddd, JHF 22.2, JFP 107.3, JFF 304.4); νmax(film)/cmϪ1 3362,
3
2
2
2982, 2926, 2854, 1452, 1386, 1254 (P᎐O), 1000 (C–F); m/z (CI,
From 190 µL of methyl benzoate ester (1.49 mmol), 468 mg
of crude oil were obtained. By flash chromatography using
petroleum ether–ethyl acetate (8 : 2), 268 mg of 9b (73%) were
isolated as a colorless oil δH (250 MHz; CDCl3) 1.33 (6H, d,
᎐
CH4) 329.167 (MHϩ, C14H28F2O4P requires 329.169), 245
(32%), 161 (84), 132 (100).
3
3
3JHH 6.2, iPr), 1.37 (6H, d, JHH 6.2, iPr), 4.89 (2H, dsept, JHP
Diisopropyl 1,1-difluoro-2-hydroxydecylphosphonate (8e)
3
and JHH 6.2, iPr), 7.45–7.50 (2H, m, Ph), 7.58–7.65 (1H, m,
From 270 µL of nonaldehyde (1.49 mmol), 637 mg of crude oil
were obtained. By bulb-to-bulb distillation (140 ЊC/9.10Ϫ2
mbar), 354 mg of 8e (86%) were isolated as a colorless oil δH
Ph), 8.12–8.16 (2H, m, Ph); δC (62.9 MHz; CDCl3) 23.9 (d, 3JCP
5.3, iPr), 24.5 (d, 3JCP 3.3, iPr), 75.2 (d, 2JCP 7.0, iPr), 115.2 (dt,
1JCP 200.9, 1JCF 273.9, CF2), 128.9, 130.8 (t, 3JCF 3.1, Ph), 132.6,
3
2
2
(250 MHz; CDCl3) 0.87 (3H, t, JHH 7.0, CH3), 1.23 (10H, m,
134.9, 188.4 (dt, JCF 24.3, JCP 14.8, C(᎐O)); δ (101.2 MHz;
᎐
P
CH2), 1.37 (12H, dd, 3JHH 6.2, 4JHP 2.8, iPr), 1.60–1.95 (4H, m,
CH2), 3.03 (1H, br s, OH), 3.66–3.88 (1H, m, CH(OH)), 4.85
CDCl3) 1.0 (t, JFP 96.5); δF (235.2 MHz; CDCl3) Ϫ110.2 (d,
2
2JFP 96.5); νmax(film)/cmϪ1 3748, 2986, 2360, 1700 (C᎐O), 1290
᎐
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 8 6 – 2 4 9 1
2489

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(P᎐O), 1010 (C–F); m/z (CI, CH ) 321.112 (MHϩ,C H F O P
requires 321.107), 219 (19%), 105 (100), 77 (21).
107 (35), 91 (21), 89 (25), 69 (38), 65 (70), 47 (17), 43 (51), 41
᎐
4
14 20
2
4
(47); m/z (CI, CH4) 342.979 (MHϩ, C7H15F2O3PI requires
342.977).
Methyl(diisopropoxyphosphonyl)difluoroethane dithioate (9c)
Diisopropyl 1,1-difluoro-2-phenyl-3-nitropropylphosphonate
To the lithiated anion 345 µL of carbon disulfide (5.70 mmol)
were added, and 30 minutes later 355 µL of methylene iodide
(5.70 mmol). By usual work-up 428 mg of crude oil were
obtained. By flash chromatography using petroleum ether–ethyl
acetate (6 : 4), 207 mg of 9c (59%) were isolated as a red oil δH
(250 MHz; CDCl3) 1.36 (12H, dd, 3JHH 6.3, 4JHP 3.2, iPr), 2.66
(3H, s, SCH3), 4.85 (2H, dsept, 3JHP and 3JHH 6.3, iPr); δC (62.9
MHz; CDCl3) 19.5 (s, SCH3), 23.5 (d, 3JCP 5.3, iPr), 24.1 (d, 3JCP
2.5, iPr), 75.0 (d, 2JCP 7.1, iPr), 117.0 (dt, 1JCP 212.2, 1JCF 270.8,
(10a)
From 521 mg of β-nitrostyrene (3.44 mmol), 755 mg of crude
oil were obtained. By flash chromatography using petroleum
ether–ethyl acetate (7 : 3), 167 mg of 10a (39%) were isolated as
a colorless oil δH (400 MHz; CDCl3) 1.28 (12H, d, 3JHH 6.3, iPr),
4.35 (1H, m, CH), 4.68 (1H, dsept, 3JHP and 3JHP6.4, iPr), 4.80
(1H, dsept, 3JHP and 3JHH 6.3, iPr), 4.88 (1H, dd, 3JHH 10.2, 3JHH
2
3
13.7, CH2), 5.21 (1H, dd, JHH 13.7, JHH 4.7, CH2), 7.35 (5H,
3
3
3
m, Ph); δC (100.6 MHz; CDCl3) 23.4 (d, JCP 5.1, iPr), 23.5 (d,
CF2), 220.0 (dt, JCP 17.3, JCF 22.1, C(᎐S)); δ (101.2 MHz;
᎐
P
3JCP 5.3, iPr), 23.9 (d, 3JCP 3.5, iPr), 24.0 (d, 3JCP 3.2, iPr), 48.2
2
CDCl3) 3.6 (t, JFP 104.5); δF (235.2 MHz; CDCl3) Ϫ99.3 (d,
2
2
2
2JFP 104.5); νmax(film)/cmϪ12982, 2936, 1466, 1454, 1386, 1276
(dt, JCP 16.3, JCF 20.3, C-2), 74.1 (d, JCP 7.3, iPr), 74.3 (dt,
3JCP and 3JCF 5.2, C-1), 74.4 (d, 2JCP 6.9, iPr), 118.5 (dt, 1JCP 215,
1JCF 266.2, CF2), 128.7, 128.9, 129.7 (s, Ph), 131.3 (br s, Ph); δP
(P᎐O), 1182, 1142, 1102, 1052, 998 (C–F) cmϪ1; m/z (EI)
᎐
306.035 (Mϩ, C9H17F2O3PS2 requires: 306.032), 286 (22%), 224
(23), 205 (76), 202 (34), 142 (27), 123 (16), 91 (100), 41 (25).
2
2
(101.2 MHz; CDCl3) 2.5 (dd, JPF 105.9, JPF 101.2); δF (235.2
MHz; CDCl3) Ϫ112.2 (1F, ddd, JFH 14.1, JFP 105.9, JFF
3
2
2
3
2
2
303.6), Ϫ114.6 (1F, ddd, JFH 18.8, JFP 101.2, JFF 303.6);
Diisopropyl 1,1-difluoro-2-phenylsulfanylmethylphosphonate
(9d)
νmax(film)/cmϪ12984, 2938, 1560, 1378, 1268 (P᎐O), 1162, 1102;
᎐
m/z (EI) 365 (Mϩ, 1%), 264 (29), 235 (100), 214 (66), 153 (29),
131 (31), 103 (31); Anal. Calcd for C15H22F2NO5P: C, 49.32; H,
6.07. Found: C, 50.18; H, 6.22%.
From 747 mg of diphenyl disulfide (3.44 mmol), 887 mg
of crude oil were obtained. By flash chromatography using
petroleum ether–ethyl acetate (8 : 2), 182 mg of 9d (49%) were
isolated as a colorless oil. δH (250 MHz; CDCl3) 1.32 (12H, dd,
3JHH 6.2, 4JHP 3.7, iPr), 4.82 (2H, dsept, 3JHP 6.4, 3JHH 6.2, iPr),
7.28–7.38 (3H, m, Ph), 7.55–7.58 (2H, m, Ph); δC (62.9 MHz;
CDCl3) 23.6 (d, 3JCP 5.0, iPr), 24.2 (d, 3JCP 3.0, iPr), 73.7 (d, 2JCP
Diisopropyl 1,1-difluoro-3-nitro-2-isopropylpropylphosphonate
(10b)
From 417 mg of (E)-3-methylnitrobutene (3.44 mmol), 674 mg
of crude oil were obtained. By flash chromatography using
petroleum ether–ethyl acetate (8 : 2), 217 mg of 10b (57%) were
isolated as a colorless oil δH (400 MHz; CDCl3) 0.96 (3H, d,
3JHH 7, CH3), 1.04 (3H, d, 3JHH 7, CH3), 1.38 (12H, dd, 3JHH 6.2,
4JHP 3.5, iPr), 2.43–2.52 (1H, m, CH), 3.10–3.25 (1H, m, CH),
4.36 (1H, dd, 2JHH14.7, 3JHH 5.2, CHb(NO2)), 4.77–4.89 (3H, m,
CHa(NO2), iPr); δC (100.6 MHz; CDCl3) 17.6 (s, CH3), 21.2
(s,CH3), 23.6 (d, 3JCP 4.6, iPr), 23.9 (d, 3JCP 3.5,iPr), 24.0 (d, 3JCP
1
1
7.0, iPr), 124.6 (dt, JCP 218.4, JCF 299.2, CF2P), 129.1, 130.2,
136.9 (s, Ph); δP (101.2 MHz; CDCl3) 3.1 (t, 2JFP 99.8); δF (235.2
2
MHz; CDCl3) Ϫ84.2 (d, JFP 99.8); νmax(film)/cmϪ12984, 2338,
1472, 1388, 1274 (P᎐O), 1116, 1000 (C–F), 750; m/z (EI)
᎐
324.078 (Mϩ, C13H19F2O3PS requires 324.076), 282 (30%), 240
(100), 159 (38), 110 (28), 94 (26), 65 (20), 41 (17).
Diisopropyl 1,1-difluoro-2-phenylselenalylmethylphosphonate
(9e)
3
3
2
3.7, iPr), 25.7 (dt, JCP and JCF 2.8, CH), 46.3 (dt, JCP 15.7,
2JCF 18.0, CH), 70.1 (dt, 3JCF and 3JCP 5.2, CH2(NO2)), 74.2 (d,
2JCP 7.2, iPr), 74.3 (d, JCP 7.3, iPr), 120.7 (dt, JCP 214.3, JCF
2
1
1
From 1.071 g of diphenyl diselenide (3.44 mmol), 1.270 g of
crude oil were obtained. By flash chromatography using
petroleum ether–ethyl acetate (8 : 2), 210 mg of 9e (50%) were
isolated as a colorless oil. δH (250 MHz; CDCl3) 1.29 (12H, dd,
3JHH 6.3, 4JHP 1.3, iPr), 4.80 (2H, dsept, 3JHP and 3JHH 6.3, iPr),
7.20–7.40 (3H, m, Ph), 7.60–7.70 (2H, m, Ph); δC (62.9 MHz;
CDCl3) 23.7 (d, 3JCP 5.0, iPr), 24.2 (d, 3JCP 3.1, iPr), 74.6 (d, 2JCP
267.8, CF2); δP (101.2 MHz; CDCl3) 5.1 (t, 2JPF 114.0); δF (235.2
3
2
2
MHz; CDCl3) Ϫ109.4 (1F, ddd, JFH 20.3, JFP 114.0, JFF
3
2
2
329.4), Ϫ116.4 (1F, ddd, JFH 20.3, JFP 114.0, JFF 329.4);
νmax(film)/cmϪ12982, 2940, 1562, 1468, 1382, 1270 (P᎐O), 1180,
᎐
1102 (C–O), 998 (C–F); m/z (EI) 332 (MHϩ, 5%), 331 (Mϩ, 1),
248 (27), 230 (100), 201 (30), 159 (44), 119 (63), 99 (55), 77 (34);
Anal. Calcd for C12H24F2O5PN: C, 43.50; H, 7.30; Found: C,
43.53; H, 7.39%.
1
1
6.9, iPr), 124.6 (dt, JCP 211.7, JCF 311.7, CF2), 129.1, 129.8,
137.7 (s, Ph); δP (101.2 MHz; CDCl3) 3.4 (t, 2JFP 94.5); δF (235.2
2
MHz; CDCl3) Ϫ85.3 (d, JFP 94.5); νmax(film)/cmϪ12984, 2938,
1468, 1378, 1272 (P᎐O), 1040 (C–F); m/z (EI) 372.017 (Mϩ,
Diisopropyl 1,1-difluoro-2,2-dihydroxyethylphosphonate (11)
᎐
C13H19F2O3PSe requires 372.021), 330 (16%), 288 (100), 158
(19), 127 (15), 94 (19), 77 (15).
To a solution of lithiophosphonate 116 µL of dimethyl form-
amide (1.49 mmol) was added. After 1 h of stirring at Ϫ78 ЊC,
the mixture was acidified by addition of 3 mL of HCl (1 M) and
warmed-up to 0 ЊC. After extraction with dichloromethylene
300 mg of crude oil were obtained. By flash chromatography
using petroleum ether–ethyl acetate (3 : 7), 240 mg of 11 (80%)
were isolated as a white solid. Crystallization in pentane–
acetone (8 : 2) afforded suitable sample for X-ray analysis (mp
Diisopropyl 1,1-difluoro-1-iodomethylphosphonate (9f)
From a THF solution (1 mL) containing 873 mg of sublimed
iodine (3.44 mmol), 370 mg of crude oil were obtained. The
crude was diluted in dichloromethylene (25 mL) and washed
with a saturated solution of NH4Cl, an aqueous solution of
Na2S2O4 (1 M), and brine. The organic layer was dried over
MgSO4 and concentrated in vacuum. By bulb-to-bulb distil-
lation (50 ЊC/8.10Ϫ2 mbar), 276 mg of 9f (70%) were isolated as
a yellow oil. δH (250 MHz; CDCl3) 1.4 (12H, dd, 3JHH 6.2, 4JHP
3.0, iPr), 4.9 (2H, dsept, 3JHP and 3JHH 6.2, iPr); δC (100.6 MHz;
CDCl3) 22.6 (d, 3JCP 5.5, iPr), 23.1 (d, 3JCP 3.2, iPr), 74.7 (d, 2JCP
7.1, iPr), 97.2 (dt, 1JCP 220.5, 1JCF 332.8, CF2); δP (101.2 MHz;
3
78–80 ЊC). δH (250 MHz; CDCl3) 1.38 (6H, d, JHH 5.9, iPr),
3
3
3
1.41 (6H, d, JHH 5.9, iPr), 4.91 (2H, dsept, JHP and JHH 6.1,
3
3
iPr), 4.5–5.5 (2H, m, OH), 5.15 (1H, dt, JPH 11.6, JFH 6.7,
CH(OH)2); δC (100.6 MHz; CDCl3) 23.5 (d, 3JCP 5.6, iPr), 24.2
3
3
2
(d, JCP 2.9, iPr), 74.7 (d, JCP 7.1, CHiPr), 89.7 (dt, JCP 15.2,
2JCF 28.3, CH(OH)2), 115.7 (dt,1JCP 202.3, JCF 268.2, CF2); δP
1
(101.2 MHz; CDCl3) 4.6 (t, 2JPF 97.8); δF (235.2 MHz; CDCl3)
2
2
3
CDCl3) Ϫ3.2 (t, JFP 86.4); δF (235.2 MHz; CDCl3) Ϫ59.8
Ϫ122.5 (dd, JPF 97.8, JHF 6.70); νmax(CHCl3)/cmϪ13600–3200
2
(d, JFP 86.4); νmax(film)/cmϪ12984, 2938, 1468, 1388, 1276
(νOH), 2950, 1470, 1390, 1220 (P᎐O), 1180, 1100, 1000 (C–F);
᎐
(P᎐O), 1120, 1100, 1066, 1002 (C–F); m/z (EI) 301 (15%), 299
(19), 285 (100), 259 (44), 173 (86), 133 (51), 127 (16), 123 (16),
Anal. Calcd for C8H17F2O5P: C, 36.65; H, 6.54. Found: C,
36.69; H, 6.54%.
᎐
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 4 8 6 – 2 4 9 1
2490

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2111–2112; (c) R. D. Chambers, R. Jaouhari and D. O’Hagan,
X-Ray analysis‡ C8H17 F2 O5 P, Mr 262.19, monoclinic, P21/a,
a 6.751(2), b 24.363(9), c 8.091(1) Å, β 101.75(2)Њ, V 1302.9(6)
ÅϪ3, Z 4, Dx 1.337 Mg mϪ3, λ(Mo-Kα) 0.71073 Å, µ 2.39 cmϪ1,
F(000) 552, T 293 K. The sample (0.52 × 0.42 × 0.37 mm) is
studied on an automatic diffractometer CAD4 NONIUS with
graphite monochromatized MoKα radiation (Fair, 1990). The
cell parameters are obtained by fitting a set of 25 high-theta
reflections. The data collection (2θmax 54Њ, scan ω/2θ 1, tmax 60 s,
range HKL: H 0,8 K 0,31 L Ϫ10,10) gives 2837 unique reflec-
tions from which 2167 with I > 2.0σ(I ). After Lorenz and polar-
ization corrections (Spek, 1997) the structure was solved with
SIR-97 (Altomare & al., 1998) which reveals the non hydrogen
atoms of the compound. After anisotropic refinement a Fourier
Difference reveals many hydrogen atoms. The whole structure
was refined with SHELXL97 (Sheldrick, 1997) by the full-
matrix least-square techniques (use of F square magnitude; x,
y, z, βij for P, O, F and C atoms, x, y, z in riding mode for H
atoms; 146 variables and 2837 observations; calc w = 1/[σ2(Fo2)
ϩ(0.076P)2 ϩ0.33P] where P = (Fo2ϩ2Fc2)/3 with the resulting
R 0.044, Rw 0.124 and Sw = 1.054 (residual ∆ρ ≤ 0.28 eÅϪ3).
Tetrahedron, 1989, 45, 5101–5108; (d ) G. M. Blackburn, D. Brown
and S. J. Martin, J. Chem. Res. (S), 1985, 92–95; (e) E. Pfund,
T. Lequeux, M. Vazeux and S. Masson, Tetrahedron Lett., 2002, 43,
2033–2036; ( f ) E. Pfund, T. Lequeux, S. Masson and M. Vazeux,
Org. Lett., 2002, 4, 843–846.
4 (a) M. Obayashi, E. Ito, K. Matsui and K. Kondo, Tetrahedron
Lett., 1982, 23, 2323–2326; (b) D. J. Burton, Z. Yang and W. Qiu,
Chem. Rev., 1996, 96, 1641–1715.
5 R. Waschbüsch, J. Carran, A. Marinetti and P. Savignac, Synthesis,
1998, 727–743 and references therein.
6 D. J. Burton and R. M. Flynn, J. Fluorine Chem., 1977, 10, 329–332.
7 (a) D. J. Burton and L. G. Sprague, J. Org. Chem., 1989, 54, 613–617;
(b) D. J. Burton, T. Ishiara and M. Maruta, Chem. Lett., 1982,
755–758.
8 (a) R. Waschbüsch, M. Samadi and P. Savignac, J. Organomet.
Chem., 1997, 529, 267–278; (b) J. Nieschalk, A. S. Batsanov,
D. O’Hagan and J. A. K. Howard, Tetrahedron, 1996, 52, 165–176.
9 (a) D. J. Burton and Z. Yang, J. Org. Chem., 1992, 57, 4676–4683; (b)
W. Huang, J. Fluorine Chem., 1992, 58, 1–8; (c) C. Hu and J. Chen,
J. Chem. Soc., Perkin Trans. 1, 1993, 327–330; (d ) A. Li and
Q. Chen, Synthesis, 1996, 606–608; (e) T. Lequeux, F. Lebouc,
C. Lopin, H. Yang, G. Gouhier and S. Piettre, Org. Lett., 2001, 3,
185–187.
10 A. McCulloch, J. Fluorine Chem., 1999, 100, 163–173.
11 (a) J. Wrobel and A. Dietrich, Tetrahedron Lett., 1993, 34, 3543–
3546; (b) G. B. Hammond and F. Benayoud, Chem. Commun., 1996,
1447–1448; (c) S. D. Taylor, C. C. Kotoris, A. N. Dinaut and
M. Chen, Tetrahedron, 1998, 54, 1691–1714.
12 (a) G. M. Blackburn and D. E. Kent, J. Chem. Soc., Perkin Trans. 1,
1986, 913–917; (b) W. Chen, M. T. Flavin, R. Filler and Z. Xu,
J. Chem. Soc., Perkin Trans. 1, 1998, 3979–3988; (c) S. D. Taylor,
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13 (a) C. Jouen, S. Lemaître, T. Lequeux and J. C. Pommelet,
Tetrahedron, 1998, 54, 10801–10810; (b) S. Gouault, J. C. Pommelet
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Acknowledgements
We are grateful to the “Conseil Régional de Basse-Normandie”
and the CNRS for the BDI financial support to AHQ, and
Professor J. M. Percy (University of Leicester U.K.) for the
helpful discussion.
‡ CCDC reference numbers CCDC 203879. See http://www.rsc.org/
suppdata/ob/b3/b301729j/ for crystallographic data in .cif or other
electronic format.
14 For the chlorination of 4a see (a) M. Mikolajczyk, A. Zatorski,
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43, 2518–2521; (b) M. Fild and M. Vahldiek, Phosphorus Sulfur
Relat. Elem., 1988, 40, 207–213.
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