A convenient AIBN-initiated radical addition of ethyl iododifluoroacetate to alkenes

Article abstract of DOI:10.1016/j.jfluchem.2008.03.002

The AIBN-initiated addition of ethyl 4-iodo-2,2-difluoroacetate to a variety of alkene substrates is described. The addition generally led to the corresponding addition products in good to excellent yields and various functional groups could be tolerated

Full text of DOI:10.1016/j.jfluchem.2008.03.002

Journal of Fluorine Chemistry 129 (2008) 986–990
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
A convenient AIBN-initiated radical addition of ethyl iododifluoroacetate to
alkenes
*
Leo Leung, Bruno Linclau
School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK
A R T I C L E I N F O
A B S T R A C T
Article history:
The AIBN-initiated addition of ethyl 4-iodo-2,2-difluoroacetate to a variety of alkene substrates is
described. The addition generally led to the corresponding addition products in good to excellent yields
and various functional groups could be tolerated under the reaction conditions.
ß 2008 Elsevier B.V. All rights reserved.
Received 5 February 2008
Received in revised form 3 March 2008
Accepted 5 March 2008
Available online 13 March 2008
Dedicated to Prof. Dennis Curran on the
occasion of receiving the 2008 ACS Award
for Creative Work in Fluorine Chemistry.
Keywords:
Addition reaction
Radical addition
Ethyl iododifluoroacetate
Fluorinated building block
2,2-Difluoroester
Iodide reduction
1. Introduction
[10], and triethylborane [11]. In the majority of cases, 1b is used as
reagent. Subsequent reduction of 2b to 3 is reported using
The synthesis of fluorinated compounds is of importance across
a number of areas, notably in pharmaceutical, agrochemical, and
materials chemistry [1]. An important subset of fluorinated
compounds contains a difluoromethylene (CF2) group [2]. This
group can be obtained by direct fluorination of ketones [3], or by a
building block approach using appropriately fluorinated synthons
NiCl2ꢀ6H2O [9c]. In addition, Burton has also reported an addition
process of 1b to alkenes leading directly to products 3 using
NiCl2ꢀ6H2O/Zn [12], and Taguchi has reported the direct formation
of the reduced product 3 when the electron deficient acrylamide
was used, with Sn as reagent [9b].
In our hands, addition of 1b to alkenes using NiCl2ꢀ6H2O/Zn
appeared to be a rather capricious process, presumably due to the
quality of the Zn metal used and/or inadequate Zn-activation. We
wish to report a convenient, high-yielding alternative in that
radical-mediated addition of 1b to alkenes was found to proceed
by simply using AIBN as initiator. Subsequent iodide reduction to
[4]. For the syntheses of a,a-difluoroesters 3 (Scheme 1), (m)ethyl
bromo and iodo difluoroacetate 1a,b are useful building blocks,
with the desired products accessible via a Reformatsky or aldol-
type reaction or via a radical-mediated addition to alkenes.
A Reformatsky process is typically performed using 1 [2,5], and
leads to adducts 2c, of which the alcohol group subsequently needs
removing to obtain 3. This is typically achieved by a 2-step Barton-
McCombie reduction process [6] via a thiocarbamate [7] or a
thiocarbonate [8] derivative. Alternatively, a radical-mediated
addition reaction using 1a,b leads to adducts 2a or 2b, with
subsequent reduction of the halide required to obtain 3. A range of
initiators have been reported, such as copper [9], sodium dithionite
afford difluoroalkane
3 was achieved in high yields using
NiCl2ꢀ6H2O/Zn or Et3B/Bu3SnH.
2. Results and discussion
2.1. AIBN-initiated addition of ethyl 4-iodo-2,2-difluoroacetate to
alkenes
AIBN is a commonly employed radical initiator in organic
synthesis. Several examples of AIBN-initiated addition of per-
fluoroalkyliodides to alkenes have been reported in the literature,
* Corresponding author. Tel.: +44 23 8059 3816; fax: +44 23 8059 6805.
E-mail address: bruno.linclau@soton.ac.uk (B. Linclau).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.03.002

L. Leung, B. Linclau / Journal of Fluorine Chemistry 129 (2008) 986–990
987
Scheme 1.
We were thus pleased to find that when difluoroacetate 1b was
reacted with a range of alkene substrates 4–10 with AIBN, the
addition products 11–17 were generally formed in good to
excellent yields (Scheme 2 and Table 1). Unfortunately, when
ethyl bromodifluoroacetate was submitted under these reaction
conditions no reaction was observed.
Scheme 2.
the earliest of which was reported in the 1960s [13]. To the best of
our knowledge, this reagent has not yet been applied in radical
additions involving iododifluoroacetates such as 1b, though an
AIBN-initiated allylation involving allyltin has been described
starting from a 2-bromo-2,2-difluoroacetamide derivative [14].
In most cases, a slight excess of difluoroacetate 1b was required
in order to achieve optimum results (Entries 2–8). When 1.5
equivalents of tetradecene 4 and 1.0 equivalent of iododifluor-
oaceate 1b were treated with AIBN (10%), a modest 54% yield of
product 11 was obtained (Entry 1). On the other hand, using a small
Table 1
AIBN-initiated addition of difluoroacetate 1b to alkene substrates
Entry
1
Alkene
Equiv
1.5
AIBN (mol%)
10%
1b (equiv)
Product
Yielda (%)
54
Tetradecene 4
1.0
2
4
1.0
10%
1.5
11
77

988
L. Leung, B. Linclau / Journal of Fluorine Chemistry 129 (2008) 986–990
Table 1 (Continued )
Entry
Alkene
Equiv
AIBN (mol%)
1b (equiv)
Product
Yielda (%)
3
4
4
4
1.0
1.0
20%
20%
1.5
1.3
11
11
83
88
5
9-Decen-1-ol 5
1.0
20%
1.3
69
6
Hex-5-en-2-one 6
1.0
1.0
1.0
20%
30%
20%
1.3
1.3
1.3
46
62
37
7b
8
6
13
N-Allyl phthalimide 7
9
Trimethyl(vinyl)silane 8
1.0
3.0
1.0
3.0
3.0
10%
10%
10%
10%
10%
1.5
1.0
1.5
1.0
1.0
66
10
11
12
13
8
15
16
86
Cyclohexene 9
9
33, 1: 2.5 (cis:trans)
70, 1: 2.0 (cis:trans)
86, 1: 3.1
Diallyl ether 10
a
Isolated yield.
b
60 8C instead of 70 8C (significant decomposition of product at 70 8C).
Scheme 3.
excess of difluoroacetate 1b (1.5 equiv) over tetradecene 4 (1.0
equiv) led to an improved yield of 77% (Entry 2). Increasing the
amount of AIBN was found to improve the yield further (Entry 3),
and an excellent yield of product 11 could still be obtained when
the amount of difluoroacetate 1b was reduced to 1.3 equiv (Entry
4). Alkanol 12 was obtained in 69% yield from 9-decen-1-ol under
similar conditions (Entry 5).
When stirring difluoroacetate 1b and hex-5-en-2-one 6 at 70 8C
for 16 h, a deep brown solution was obtained which, after
purification by column chromatography, afforded adduct 13 in
46% yield (Entry 6). The colour of the reaction mixture was
significantly less intense when the reaction was performed at 60 8C
and an improved yield of 62% was obtained using 30% of AIBN
(Entry 7). However, when N-allyl phthalimide 7 was employed, the
desired product 14 was only obtained in 37% yield (Entry 8).
For volatile substrates such as trimethyl(vinyl)silane 8,
cyclohexene 9 and diallyl ether 10, an excess (3 equivalents) of
the alkene was necessary to deliver good yields of the correspond-
ing adducts 15–17 (Entries 10, 12–13). Hence, when iododifluor-
oacetate 1b was used in small excess (1.5 equiv), the yield of
product 15 was significantly lower than when an excess (3.0 equiv)
of the corresponding alkenes 8 was employed (Entries 10 vs. 9).
Similarly, when excess cyclohexene 9 was employed (Entry 12),
adduct 16 was obtained in 70% yield (mixture of cis/trans, 1:2.5), in
contrast to the 33% yield of 16 obtained when using a small excess
of iododifluoroacetate 1b (Entry 11). THF-derivative 17 was also
synthesised from diallyl ether 10 (3.0 equiv) in a similar manner
(Entry 12).
2.2. Subsequent iodide reduction
Iodide reduction of the addition product 11 was initially
attempted using AIBN and Bu3SnH in refluxing toluene (Scheme 3),
but the desired product was not formed. A second product was
isolated which likely resulted from the lactonisation of 11 [15].
Fortunately, ambient-temperature initiation of the same reduction
using Et3B instead of AIBN gave difluoroester 18 in 68% yield [16].
Alternatively, iodide reduction could also be achieved using Zn/
NiCl2ꢀ6H2O [9c] in wet THF to afford difluoroester 18 in 82% yield
(Scheme 3).
3. Conclusion
We have successfully established the AIBN-initiated addition of
ethyl 4-iodo-2,2-difluoroacetate to a variety of alkene substrates.
Subsequent iodide reduction of the addition products could be
achieved using Zn/NiCl2ꢀ6H2O or Et3B/Bu3SnH, as demonstrated in
the conversion of iodide 11 to difluoroester 18. The process will

L. Leung, B. Linclau / Journal of Fluorine Chemistry 129 (2008) 986–990
989
serve as an alternative to existing methods that enables the facile
0.2 mmol) in dichloroethane (3.3 mL) at 70 8C for 16 h. The crude
was purified by column chromatography (EtOAc/petroleum ether
15 ! 30%) to afford a colourless oil (282 mg, 69%). 19F NMR
(282 MHz, CDCl3) ꢂ102.3 (d, J = 262.0 Hz), ꢂ107.0 (d, J = 262.0 Hz);
1H NMR (400 MHz, CDCl3) 4.36 (2H, q, J = 7.0 Hz), 4.23 (1H, dtd,
J = 9.0, 7.0, 4.5 Hz), 3.65 (2H, t, J = 6.5 Hz), 2.92 (1H, dtd, J = 18.5,
15.5, 6.5 Hz), 2.74 (1H, dddd, J = 18.0, 15.5, 12.5, 7.0 Hz), 1.87–1.69
and 1.61–1.29 (15H, m), 1.38 (3H, t, J = 7.0 Hz); 13C NMR (100 MHz,
CDCl3) 163.6 (t, J = 32.5 Hz), 115.3 (t, J = 251.5 Hz), 63.4, 63.1,
45.5 (t, J = 23.0 Hz), 32.9, 29.6, 29.4, 28.6, 25.8, 23.4 (t, J = 3.5 Hz),
14.3.
introduction of an
a,a-difluoroalkyl fragment.
4. Experimental
4.1. General experimental procedures
1H and 13C NMR spectra were recorded at room temperature on
a Bru¨ker DPX400 or AV300 spectrometer as indicated. Chemical
shifts are quoted in ppm relative to residual solvent peaks as
appropriate. Low resolution ES mass spectra and EIMS were
recorded on a Waters ZMD and Thermoquest TraceMS Quadrapole
spectrometer respectively. Infrared spectra were recorded as neat
films on a Nicolet Impact 380 ATR spectrometer. Melting points
were recorded on a Gallencamp Melting Point Apparatus and are
uncorrected.
4.2.3. Ethyl 2,2-difluoro-4-iodo-7-oxooctanoate (13) [9c]
Ester 13 was prepared from hex-5-en-2-one (118
mL,
1.0 mmol), difluoroacetate 1b (324 mg, 1.3 mmol) and AIBN
(49.2 mg, 0.3 mmol) in dichloroethane (3.3 mL) at 60 8C for 16 h.
The crude was purified by column chromatography (EtOAc/
petroleum ether 15:85) to afford a pink oil (216 mg, 60%) which
Column chromatography was performed on 230–400 mesh
Matrex silica gel. Preparative HPLC was carried out using a Biorad
needed to be stored in the freezer to minimise decomposition. 19
F
Biosil D 90-10, 250 mm ꢁ 22 mm column eluting at 20 mL minꢂ1
,
NMR (282 MHz, CDCl3) ꢂ102.4 (d, J = 264.5 Hz), ꢂ106.6 (d,
J = 264.5 Hz); 1H NMR (400 MHz, CDCl3) 4.30 (2H, q, J = 7.5 Hz),
4.21 (1H, dtd, J = 10.5, 7.0, 4.0 Hz), 2.89 (1H, dtd, J = 18.0, 15.5,
6.5 Hz), 2.77–2.54 (3H, m), 2.13 (3H, s), 2.05 (1H, dddd, J = 15.0, 8.5,
6.5, 4.0 Hz), 1.94 (1H, m), 1.33 (3H, t, J = 7.0 Hz); 13C NMR
(100 MHz, CDCl3) 206.5, 163.3 (t, J = 32.5 Hz), 115.0 (t,
J = 251.5 Hz), 63.3, 45.4 (t, J = 23.0 Hz), 43.5, 34.1, 30.1, 22.2, 13.9.
connected to a Kontron 475 refractive index detector. Reactions
were monitored by TLC (Merck) with detection by KMnO4 or
anisaldehyde stains.
Reaction solvents were dried before use as follows: THF and
Et2O were distilled from sodium/benzophenone; CH2Cl2 and Et3N
were distilled from CaH2; toluene was distilled from sodium. Ethyl
iododifluoroacetate (light pink) was purchased from Fluorochem
Ltd and in most cases was used without further purification. If the
purchased ethyl iododifluoroacetate was deep purple in colour, the
reagent was dissolved in Et2O, washed with sat. Na2S2O3 solution
and concentrated in vacuo to give a light yellow oil. Zinc metal was
activated by stirring with 1 M HCl and washed with H2O followed
by anhydrous THF. All reaction vessels were flame dried under
vacuum prior to use and all experiments were carried out under a
nitrogen atmosphere. All other reagents were purchased from
commercial sources and used without further purification.
4.2.4. Ethyl 2,2-difluoro-4-iodo-5-(1,3-dioxoisoindolin-2-
yl)pentanoate (14)
Ester 14 was prepared from N-allyl phthalimide (187 mg,
1.0 mmol), difluoroacetate 1b (324 mg, 1.3 mmol) and AIBN
(32.8 mg, 0.2 mmol) in dichloroethane (3.3 mL) at 70 8C for
16 h. The crude was purified by column chromatography
(EtOAc/petroleum ether 15:85) to afford
a colourless oil
(161 mg, 37%). IR (cmꢂ1) 2985 w, 1767 m, 1709 vs, 1614 w,
1468 w, 1430 m, 1392 s; 19F NMR (282 MHz, CDCl3) ꢂ102.1 (d,
J = 265.0 Hz), ꢂ106.2 (d, J = 264.0 Hz); 1H NMR (400 MHz, CDCl3)
7.90–7.86 (2H, m), 7.78–7.73 (2H, m), 4.59 (1H, m), 4.34 (2H, q,
J = 7.0 Hz), 4.14 (1H, dd, J = 14.5, 8.5 Hz), 3.97 (1H, dd, J = 14.5,
7.5 Hz), 2.94 (1H, dtd, J = 17.5, 16.0, 7.5 Hz), 2.79 (1H, dddd,
J = 17.5, 16.0, 13.0, 6.0 Hz), 1.36 (3H, t, J = 7.0 Hz); 13C NMR
(100 MHz, CDCl3) 168.1, 163.5 (t, J = 33.0 Hz), 134.8, 132.1, 124.1,
115.3 (t, J = 252.5 Hz), 63.8, 46.4, 43.2 (t, J = 23.5 Hz), 15.9 (m),
14.3; ES+ m/z (%) 460 ((M+Na)+, 90), 492 ((M+Na+MeOH)+, 100);
HRMS (ES+) for C15H14F2INO2 (M+H)+: Calcd 438.0008; Measured
438.0002.
4.2. Typical procedures forthe preparationof 2,2-difluoro-4-iodo esters
AIBN was added to a solution of alkene and iododifluoroacetate
1b in dichloroethane. The mixture was stirred at 70 8C for 16 h,
followed by concentration in vacuo. The crude mixture was
purified by column chromatography to afford the desired 2,2-
difluoro-4-iodo esters.
4.2.1. Ethyl 2,2-difluoro-4-iodohexadecanoate (11)
Ester 11 was prepared from tetradecene 4 (92% purity; 275
mL,
1.0 mmol), difluoroacetate 1b (374 mg, 1.5 mmol) and AIBN
(16.4 mg, 0.1 mmol) in dichloroethane (3.3 mL) at 70 8C for 16 h.
The crude was purified by column chromatography (EtOAc/
petroleum ether 0 ! 5%) to afford a colourless oil (395 mg, 88%).
IR (cmꢂ1) 2923 vs, 2853 s, 1770 vs, 1466 m, 1432 w, 1374 m,
1338 w, 1299 m, 1183 s, 1071 vs; 19F NMR (282 MHz, CDCl3) ꢂ102.3
(d, J = 263.0 Hz), ꢂ107.0 (d, J = 264.5 Hz); 1H NMR (400 MHz, CDCl3)
4.35 (2H, q, J = 7.0 Hz), 4.23 (1H, dtd, J = 8.5, 7.0, 4.5 Hz), 2.92 (1H,
dtd, J = 18.5, 16.0, 6.5 Hz), 2.74 (1H, dddd, J = 18.0, 16.0, 13.0, 7.5 Hz),
1.87–1.69 (2H, m), 1.59–1.21 (20H, m), 1.38 (3H, t, J = 7.0 Hz), 0.89
(3H, t, J = 7.0 Hz); 13C NMR (100 MHz, CDCl3) 163.6 (t, J = 32.0 Hz),
115.4 (t, J = 251.5 Hz), 63.4, 45.6 (t, J = 22.5 Hz), 32.1, 29.79, 29.76,
29.70, 29.66, 29.55, 29.51, 28.7, 23.5 (t, J = 4.0 Hz), 22.9, 14.3, 14.1;
ES+ m/z (%) 469 ((M+Na)+, 100); HRMS (ES+) for C18H33F2IO2
(M+Na)+: Calcd 469.1386; Measured 469.1378.
4.2.5. Ethyl 2,2-difluoro-4-iodo-4-(trimethylsilyl)butanoate (15) [9c]
Ester 15 was prepared from vinyltrimethylsilane (440
mL,
3.0 mmol), difluoroacetate 1b (249 mg, 1.0 mmol) and AIBN
(16.4 mg, 0.1 mmol) in dichloroethane (3.3 mL) at 70 8C for 16 h.
The crude was purified by column chromatography (EtOAc/
petroleum ether 0 ! 5%) to afford a colourless oil (302 mg, 86%).
19F NMR (282 MHz, CDCl3) ꢂ102.5 (d, J = 260.0 Hz), ꢂ108.0 (d,
J = 260.0 Hz); 1H NMR (400 MHz, CDCl3) 4.36 (2H, q, J = 7.0 Hz),
3.11 (1H, m), 2.68–2.58 (2H, m), 1.38 (3H, t, J = 7.0 Hz), 0.19 (9H, s);
13C NMR (100 MHz, CDCl3) 163.9 (t, J = 32.5 Hz), 115.8 (t,
J = 249.0 Hz), 63.3, 39.2 (t, J = 24.0 Hz), 14.0, 4.5, ꢂ2.3.
4.2.6. Ethyl 2,2-difluoro-2-(2-iodocyclohexyl)acetate (16) [9c,10a]
Ester 16 was prepared from cyclohexene (304
mL, 3.0 mmol),
difluoroacetate 1b (249 mg, 1.0 mmol) and AIBN (16.4 mg,
0.1 mmol) in dichloroethane (3.3 mL) at 70 8C for 16 h. The crude
was purified by column chromatography (EtOAc/petroleum ether
5 ! 20%) to afford a colourless oil (234 mg, 70%, cis/trans 1.0:2.1).
4.2.2. Ethyl 2,2-difluoro-5-hydroxy-4-iodododecanoate (12) [9c]
Ester 12 was prepared from 9-decen-1-ol (184
mL, 1.0 mmol),
difluoroacetate 1b (324 mg, 1.3 mmol) and AIBN (32.8 mg,

990
L. Leung, B. Linclau / Journal of Fluorine Chemistry 129 (2008) 986–990
19F NMR (282 MHz, CDCl3) ꢂ106.1 (trans; d, J = 264.5 Hz), ꢂ110.0
(cis; d, J = 262.0 Hz), ꢂ111.8 (cis + trans; d, J = 262.0 Hz); 1H NMR
(400 MHz, CDCl3) 4.66 ꢂ 4.29 (3Hcis+trans, m), 2.73 ꢂ 2.61 (1Hcis+-
trans, m), 2.34 ꢂ 1.37 (8Hcis+trans, m), 1.343 (3Htrans, t, J = 7.0 Hz),
1.340 (1Hcis, t, J = 7.0 Hz); 13C NMR (100 MHz, CDCl3) 163.8 (t,
J = 32.5 Hz), 163.7 (t, J = 32.5 Hz), 116.4 (t, J = 251.5 Hz), 115.3 (t,
J = 253.5 Hz), 63.1, 48.1 (t, J = 21.0 Hz), 47.0 (t, J = 22.0 Hz), 39.1,
37.3, 28.8 (t, J = 4.0 Hz), 26.4, 25.3 (t, J = 3.0 Hz), 25.1, 24.4 (m),
23.4, 22.3 (t, J = 2.5 Hz), 22.2, 13.92, 13.90.
Acknowledgement
We thank Cancer Research Technology for funding.
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,
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(1Hmin, dd, J = 10.0, 8.5 Hz), 3.04 (1Hmaj, dd, J = 11.0, 9.5 Hz), 2.74
(1Hmaj, m), 2.55 (1Hmaj, m), 2.42 ꢂ 1.96 (4Hmin + 2Hmaj, m), 1.35
(3Hmaj+min, t, J = 7.0 Hz); 13C NMR (100 MHz, CDCl3) 163.6 (t,
J = 32.5 Hz), 115.6 (t, J = 249.5 Hz), 115.4 (t, J = 32.5 Hz), 73.9, 73.7,
73.4, 71.5, 63.1, 47.6, 45.1, 40.0, 37.1 (t, J = 22.5 Hz), 36.6, 31.8 (t,
J = 23.0 Hz), 25.0, 13.9, 7.3, 3.7.
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4.3. Ethyl 2,2-difluorohexadecanoate (18) [12]
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(b) O. Kitagawa, A. Miura, Y. Kobayashi, T. Taguchi, Chem. Lett. (1990) 1011–1014;
(c) Z.-Y. Yang, D.J. Burton, J. Org. Chem. 56 (1991) 5125–5132;
(d) K. Sato, M. Omote, A. Ando, I. Kumadaki, J. Fluorine Chem. 125 (2004) 509–515.
[10] (a) F. Xiao, F. Wu, Y. Shen, L. Zhou, J. Fluorine Chem. 126 (2005) 63–67;
(b) F. Wu, F. Xiao, X. Yang, Y. Shen, T. Pan, Tetrahedron 62 (2006) 10091–10099.
[11] B. Moreno, C. Quehen, M. Rose-He´le`ne, E. Leclerc, J.-C. Quirion, Org. Lett. 9 (2007)
2477–2480.
[12] (a) Z.-Y. Yang, D.J. Burton, J. Chem. Soc., Chem. Commun. (1992) 233–234;
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[13] (a) N.O. Brace, J. Org. Chem. 27 (1962) 4491–4498;
Reviews
(a) NiCl2ꢀ6H2O procedure: A drop of water was added to a mixture
of iodide 11 (180 mg, 0.404 mmol), Zn (52.8 mg, 0.808 mmol)
and NiCl2ꢀ6H2O (9.6 mg, 0.0808 mmol) in THF (1.1 mL) and it
was stirred at r.t. for 16 h. The solvent was evaporated in vacuo
and the crude was purified by column chromatography
(petroleum ether) to afford a colourless oil (106 mg, 82%).
19F NMR (282 MHz, CDCl3) ꢂ106.2; 1H NMR (400 MHz, CDCl3)
4.33 (2H, q, J = 7.0 Hz), 2.11–1.99 (2H, m), 1.50–1.40 (2H, m),
1.38–1.22 (22H, m), 1.36 (3H, t, J = 7.0 Hz), 0.89 (3H, t,
J = 6.5 Hz); 13C NMR (100 MHz, CDCl3) 164.6 (t, J = 33.0 Hz),
116.6 (t, J = 248.0 Hz), 62.8, 34.7 (t, J = 23.0 Hz), 32.1, 29.82,
29.79, 29.73, 29.55, 29.52, 29.4, 29.2, 22.9, 21.6 (t, J = 4.5 Hz),
14.3, 14.1.
(b) N.O. Brace, J. Fluorine Chem. 108 (2001) 147–175;
(c) N.O. Brace, J. Fluorine Chem. 96 (1999) 101–127;
(d) N.O. Brace, J. Fluorine Chem. 93 (1999) 1–25;
(e) W.R. Dolbier Jr., Top. Curr. Chem. 192 (1997) 97–163;
(f) W.R. Dolbier Jr., Chem. Rev. 96 (1996) 1557–1584.
[14] J.L. Roberts, J. Borgese, C. Chan, D.K. Keith, C.-C. Wei, Heterocycles 35 (1993) 115–
120.
[15] The IR of the crude reaction mixture (still contaminated with alkyl tin residues)
shows a strong absorption band at 1811 cmꢂ1, which is characteristic for 2,2-
difluoro-g-lactones (Ref. [10a]). In addition, ES MS analysis shows the (M+H)+
peak and (M+H+MeOH)+, and the 1H NMR of the crude reaction mixture shows
characteristic signals at 4.61, 2.81, and 2.30 ppm (Ref. [10a]). Lactonisation of
such adducts is reported under basic conditions—see Ref. [10a].
[16] K. Miura, Y. Ichinose, K. Nozaki, K. Fugami, K. Oshima, K. Utimoto, Bull. Chem. Soc.
Jpn. 62 (1989) 143–147.
(b) Et3B procedure: Et3B (1 M solution in hexane; 46.5
46.5 mol) was added to a solution of iodide 11 (199 mg,
0.465 mmol) and Bu3SnH (193 L, 0.696 mmol) in toluene
mL,
m
m
(2.3 mL) and the mixture was stirred at r.t. for 16 h. The
reaction mixture was then filtered through K2CO3, concen-
trated in vacuo and purified by column chromatography
(petroleum ether) to afford a colourless oil (96.6 mg, 68%).