Rearrangement and double fluorination in the deiodinative fluorination of neopentyl iodide with xenon difluoride

Article abstract of DOI:10.1016/S0022-1139(99)00234-1

Alkyl iodides give products from the neopentyl rearrangement on reaction with xenon difluoride. Neopentyl iodide performs a double rearrangement and yields a gem-difluoro product, 2,2-difluoro-3-methylbutane. Studies of the mechanism show that an alkene intermediate is involved in the double rearrangement process. Alkenes can be substituted as substrates in reaction with xenon difluoride-iodine to give gem-difluoro products. ¹³C Labeling verifies the skeletal rearrangement process.

Full text of DOI:10.1016/S0022-1139(99)00234-1

Journal of Fluorine Chemistry 102 (2000) 11±15
Rearrangement and double ¯uorination in the deiodinative ¯uorination
of neopentyl iodide with xenon di¯uoride
Timothy B. Patrick*, Likang Zhang, Quinhua Li
Department of Chemistry, Southern Illinois University, Edwardsville, IL 62026, USA
Received 14 April 1999; received in revised form 6 June 1999; accepted 28 June 1999
Dedicated to Professor Paul Tarrant on the occasion of his 85th birthday
Abstract
Alkyl iodides give products from the neopentyl rearrangement on reaction with xenon di¯uoride. Neopentyl iodide performs a double
rearrangement and yields a gem-di¯uoro product, 2,2-di¯uoro-3-methylbutane. Studies of the mechanism show that an alkene intermediate
is involved in the double rearrangement process. Alkenes can be substituted as substrates in reaction with xenon di¯uoride±iodine to give
gem-di¯uoro products. 13C Labeling veri®es the skeletal rearrangement process. # 2000 Elsevier Science S.A. All rights reserved.
Keywords: Alkyl iodides; Rearrangement; Xenon di¯uoride; Gem-difuorination
1. Introduction
Patrick and Zhang showed that cyclization reactions of
alkenyl iodides also follow a carbocation path as 6-endo-trig
cyclization is favored over the 5-exo-trig process [11].
The ¯uorination of organic iodine compounds with xenon
di¯uoride produces organic iodine di¯uorides. Aromatic
iodine compounds thus yield aryl iodine di¯uorides that
are useful as ¯uorinating agents [1,2].
Ar I X!eF2 Ar IF2 ‡ Xe:
Aliphatic iodine compounds produce alkyl iodine di¯uor-
ides that decompose to give alkyl ¯uorine compounds.
Janzen and coworkers [3,4,5] gave the ®rst report of the
conversion of alkyl iodides to alkyl ¯uorides (deiodinative
¯uorination), which was later veri®ed by Forster and Downs
[6]. The studies were limited to the conversion of methyl
iodide to methyl ¯uoride as ¯uorination of isopropyl iodide
gave unworkable mixtures.
In a continuation of our studies on deiodinative ¯uorina-
tion reactions of alkyl iodides with xenon di¯uoride, we ®nd
some novel double neopentyl-type rearrangement reactions
accompanied by ¯uorination. In this paper we describe the
details of these studies.
2. Results and discussion
Reaction of neopentyl iodide (1) with xenon di¯uoride at
08C gives a purple solution that could be partially puri®ed by
distillation at 358C. Preparative gas chromatography fur-
nishes a pure sample. The structure of the product is shown
by spectroscopic analysis and independent synthesis from 3
to be 2,2-di¯uoro-3-methylbutane (2).1
CH3I ! ‰CH3IF2Š ! CH3F ‡ IF:
Della and Head used deiodinative ¯uorination to prepare
several strained bridgehead ¯uorides, such as ¯uorocubane
[7,8]. Carbocations are postulated as intermediates in the
formation of the ¯uorinated compounds [9,10].
1 Adcock et al. [12] report that aerosol fluorination of neopentyl bromide
produces mixtures of fluorinated products containing 2, 2-methyl-2-butene
and mainly perfluorisobutane. They observe rearrangement products
involving postulated carbocation and trivalent bromine difluoride inter-
mediates.
* Corresponding author.
0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 2 3 4 - 1

12
T.B. Patrick et al. / Journal of Fluorine Chemistry 102 (2000) 11±15
Two other examples of double neopentyl-type rearrange-
ment reactions are shown below. Thus, both 1-iodo-2-
methylpropane (4) and triphenylethyl iodide (5) rearrange
to give a the gem-di¯uoro products, 6 and 7, respectively.
Reaction of the iodo substrates 8, 9, 10 with xenon di-
¯uoride also produces rearrangement products (11,12,13),
but only one ¯uorine atom is found in the product. The
results are shown in Table 1.
Two different tests give insight into the proposed mechan-
ism. In the ®rst test 2-methyl-2-butene (14), a suggested
intermediate in the scheme, reacts with xenon di¯uoride and
iodine by the Shellhamer method [13], to give 2,2-di¯uoro-
3-methyl-2-butene (2) in good yield.
A mechanistic scheme shown below accounts for the
results obtained. Neopentyl iodide (1) is converted into the
iodine di¯uoride (A) that produces a rearranged carbocation
(B) on loss of IF and F . Mono¯uorination occurs as a result
of the standard neopentyl type-rearrangement followed by
attack of ¯uoride ion on B. Double ¯uorination requires
formation of 2-methyl-2-butene (14) that reacts with iodine
¯uoride followed by another reaction with xenon di¯uoride
to give the iodine di¯uoride (C). C loses IF and F and
rearranges to a ¯uorine stabilized carbocation (D) that reacts
with F to give the di¯uorinated product (2).
A similar reaction with methylenecyclopentane (15) as
the alkene substrate gives di¯uorocyclohexane (16) in good
yield. The generality of this method as a synthetic procedure
is currently being studied.
TABLE 1
Monofluorination products
Starting material
Product
A second test of the mechanism involves a study of the
skeletal rearrangement by use of 13C labeled neopentyl
iodide (13C-1). The synthesis of neopentyl iodide with a
13C label in the methylene position is given below. The label
is introduced by reaction of t-butyl lithium with 13CO2.
Conversion of the acid to the alcohol and on to the iodide is
accomplished in well-known procedures. The ®nal 13C-
labeled neopentyl iodide contains about 5% 2-iodo-2-
methylbutane with 13C located in the 3-position. The pro-
duct arises from minor neopentyl rearrangement occurring

T.B. Patrick et al. / Journal of Fluorine Chemistry 102 (2000) 11±15
13
during the preparation of the iodide with methyltriphenox-
yphosphonium iodide [14,15].
butene, and methylenecyclopentane, were purchased from
Aldrich Chemical Co., Milwaukee, Wisconsin.
3.1. 2,2-Difluoro-3-methylbutane (2)
Neopentyl iodide (0.5 mmol, 100 mg, 1) was placed in a
10 ml vial equipped with a re¯ux condenser. A drying tube
®lled with CaCl2 was connected to the condenser. Deuter-
ated chloroform (2 ml) and xenon di¯uoride (1.5 mmol,
270 mg) were added and the resulting mixture was stirred
at room temperature for 2 h. The purple reaction mixture
was distilled at 708C to produce a purple distillate which
contained the product and CDCl3. The purple color was
removed by addition of sodium thiosulfate. The purple
reaction mixture showed only two components by gas
chromatography (Gow Mac series 150 Thermal Conductiv-
ity Detector, 20% DC-200 on 80/100 mesh Chrom P col-
umn, 5 ft  0.25 in, ¯ow rate 20 cc/min of nitrogen, column
temperature 238C). Compound 2 was isolated by trapping
the column eluent in a glass tube at 708C. The product
gave the following data: ms 88 (M-HF); calculated 88 (M-
Reaction of the 13C-labeled neopentyl iodide (13C-1) with
xenon di¯uoride gives the gem-di¯uoro product (13C-2)
with the 13C label in the 3-position. A small amount of
13C labeled 2-methyl-2-butene was also observed. The 13C
label in the 3-position of (13C-2) is the expected result for
the mechanism outlined. The results from the labeling study
verify the skeletal rearrangement path outlined in the
mechanistic scheme.
1
HF); H-NMR (CDCl3, TMS) d 1.00 (d, J = 4.7 Hz, CH3,
6H), 1.52 (t, J = 18.9 Hz, CF2CH3, 3H), 2.04 (m, 8 lines,
CH, 1H); 19F-NMR (CDCl3, TFA) d 21.67 (CF2, d of q,
JCH3CF2 = 18.35, JCHCF2 = 11.29); 13C-NMR (CDCl3,
TMS) d 16.62 (s, CH3), 20.80 (s, CH3), 35.66 (s, CH),
126.1 (t, J = 249.8 Hz, CF2).
In conclusion we present a novel rearrangement of neo-
pentyl iodide to a gem-di¯uoro product. The reaction
involves a double rearrangement through an alkene inter-
mediate. Substrates that do not form alkene intermediates
show only the mono-¯uorinated product from the normal
neopentyl rearrangement. 13C labeling experiments verify
the skeletal rearrangement path.
An unambiguous synthesis of 2 was accomplished as
follows. 3-Methyl-2-butanone (2 mmol, 3) and diethylami-
nosulfur tri¯uoride (DAST, 2.4 mmol) were mixed in an
NMR tube in CDCl3 overnight to produce 2 with spectral
properties identical to the product obtained from neopentyl
iodide.
The product 2 is also obtained from reaction of 2-methyl-
2-butene (14) with XeF2 and I2 following the method of
Shellhamer et al. [13]. 2-Methyl-2-butene (2 mmol) and
XeF2 (2.4 mmol)/I2 (1.2 mmol) were mixed in an NMR tube
in CDCl3 overnight to produce 2,2-di¯uoro-3-methylbutane
without contamination of other products and identi®ed by
comparison of spectral data previously obtained for 2.
3. Experimental details
All nuclear magnetic resonance (NMR) spectra were
recorded on a Varian UNITY plus 300 MHz Spectrometer.
The proton (1H) NMR spectra were recorded at
300.05 MHz. Chemical shifts were reported as parts per
million (ppm) down ®eld from tetramethylsilane (TMS) in d
units. 13C NMR spectra were recorded at 75.46 MHz and
were reported in ppm with the center line of the triplet at
77.00 ppm for deuterated chloroform as the reference. 19F
NMR spectra were recorded at 282.3 MHz with external
tri¯uoroacetic acid (TFA, d ˆ 0.00 ppm, TFA is 76 ppm
up®eld from CFCl3) as the reference. Deuterated chloro-
form (CDCl3) was used as the solvent in all cases. Mass
spectral analysis was done by Dr. Howard Hendrickson
using a Varian Saturn 2000 GC/MS.
3.2. 2,2-Difluorobutane (6)
1-Iodo-2-methylpropane (0.5 mmol, 92 mg, 4) was
placed in a 10 ml vial equipped with a re¯ux condenser.
A drying tube ®lled with CaCl2 was connected to the
condenser. Deuterated chloroform (2 ml) and xenon di¯uor-
ide (1.5 mmol, 270 mg) were added and the resulting mix-
ture was stirred at room temperature for 2 h. The purple
reaction mixture was distilled at 708C to give 6 in 86% yield.
1H-NMR (CDCl3, TMS) d 1.01 (t, J = 7.5 Hz, CH3, 3H),
1.57 (t, CH3CF2, J = 18.3 Hz, 3H), 1.84 (m, CH2, 2H);
Xenon di¯uoride (XeF2) was purchased form PCR Incor-
porated, Gainesville, Florida. Diethylaminosulfur tri¯uor-
ide (DAST), neopentyl iodide, 2-phenyl-1-propanol,
cyclopropylmethanol, 3-methyl-2-butanone, 2-methyl-2-
19F-NMR (CDCl3, TFA)
d
16.8 (t of q, CF2,
JCH3CF2 = 15.5 Hz, JCH2CF2 = 19.5 Hz,), lit. [16] d 17.3
(t of q, CF2, JCH3CF2 = 15 Hz, JCH2CF2 = 18.5 Hz).

14
T.B. Patrick et al. / Journal of Fluorine Chemistry 102 (2000) 11±15
3.3. 2,2-Difluoro-1,1,2-triphenylethane (7)
A drying tube ®lled with CaCl2 was connected with
the condenser. CDCl3 (3 ml) and XeF2 (1.0 mm) were
added and the resulting mixture was stirred at room
temperature for 4 h. The ®nal product was identi®ed as
2-¯uoro-1-phenylpropane (13) in 85% yield. 1H-NMR
(CDCl3, TMS) d 1.31±1.41 (d of d, CH3, JCH = 3.0 Hz,
JCF = 24.0 Hz, 3H), 2.79±3.08 (m, CH2, 2H), 4.77±4.98
(m, CH, 1H) 6.98±7.66 (m, Ar-H, 5H); 19F-NMR
(CDCl3, TFA) d 94.5 (m, CHF); 13C-NMR (CDCl3,
The required iodo substrate, 1-Iodo-2,2,2-triphenylethane
(5), was obtained through a series of reactions starting with
triphenylacetic acid. The acid was reduced to the alcohol
with LAH followed by conversion to the tosylate which was
displaced with iodide. The overall yield of the sequence was
8%.
1-Iodo-2,2,2-triphenylethane (5, 0.5 mmol) was placed
into a 10 ml vial equipped with a re¯ux condenser. A drying
tube ®lled with CaCl2 was connected with the condenser.
CDCl3 (3 ml) and XeF2 (0.75 mmol) were added and the
resulting mixture was stirred at room temperature for 4 h.
1,1-Di¯uoro-1,2,2-triphenylethane (7) was obtained in 40%
yield after removal of the solvents. 19F-NMR (CDCl3, TFA)
TMS) d 20.55 (d, J = 22.48 Hz, CH3), 43.23 (d,
J = 21.43 Hz, CH2), 91.03 (d, J = 168.35 Hz, CHF),
126.51±137.30 (m, Ar-C).
d
19.9 (d, J = 12 Hz); 1H-NMR (CDCl3, TMS) d 7.6±7.0
4. Difluorocyclohexane (16)
(m, aromatic), 4.62 (t, J = 12 Hz), ms 294 (calc. 294). An
identical set of spectra were obtained when 1,1,2-triphe-
nyethene was reacted with XeF2/I2.
Methylenecyclopentane (15, 1.2 mmol, 100 mg), I2
(1.2 mmol, 310 mg) and XeF2 (2.4 mmol, 430 mg) in
1.5 ml of CDCl3 were stirred at room temperature for
3 h. Di¯uorocyclohexane (16) was obtained in 80% yield
after distillation. 1H-NMR (CDCl3, TMS) d 1.42±1.90 (ring,
m); 13C-NMR (CDCl3, TMS) d 22.90 (m), 24.36 (m), 34.09
3.4. Fluorocyclobutane (11)
Cyclopropylmethyl iodide (8, 0.5 mmol, 90 mg), CDCl3
(3 ml) and XeF2 (0.75 mmol, 130 mg) were allowed to react
for 4 h. The purple reaction mixture was distilled at 608C to
1
(m), 123.63 (CF2, J = 245 Hz); H-NMR (CDCl3, TMS) d
1.1±2.1 (m), 19F-NMR (CDCl3, TFA) d 19.46 (m, CF2);
lit. [16] d 20 (average of axial and equitorial).
1
give 11 in 30% yield. H-NMR (CDCl3, TMS) d 2.15 (m,
CH2, 4H), 2.30 (m, CH2, 2H), 4.91 (d of t, CH, Jgem
HF = 59 Hz, 1H). 19F-NMR (CDCl3, TFA) d 84.0 (m,
CHF).
An unambiguous synthesis of ¯uorocyclobutane was
accomplished from reaction of cyclobutanol (2 mmol)
and DAST (2.4 mmol) in an NMR tube in CDCl3 overnight.
1H-NMR (CDCl3) d 2.1±2.4 (ring, m), 4.91 (d of t, CH, Jgem
HF ˆ 59 Hz). 19F-NMR (CDCl3, TFA) d 84.0 (m, CHF).
13
4.1. 1-13C-1-Iodo-2,2-dimethylpropane (bf ꢀ C 2†)
To a solution of t-butyl magnesium chloride (2 M,
100 ml) in a brown air-tight bottle was introduced the
contents from a 1 l cylinder of 13CO2 at 08C over a
20 min period. The contents became slightly opaque. The
mixture was poured onto ice and acidi®ed with dilute HCl.
The ether extract was dried by ®ltration through MgSO4 and
concentrated to give 1.79 g of 1-13C-2,2-dimethylpropanoic
3.5. 1-Fluoro-2-phenylethane (12)
1
1-Iodo-2-phenylethane (9) was obtained in two steps
from conversion of the alcohol to the tosylate and then to
the iodide in 40% yield. The iodide 9 (1.0 mmol, 234 mg)
was placed in a 10 ml vial equipped with a re¯ux condenser.
A drying tube ®lled with CaCl2 was connected with the
condenser. CDCl3 (3 ml) and XeF2 (2.2 mmol) were added
and the resulting mixture was stirred at room temperature
for 4 h. The product 1-¯uoro-2-phenylethane (12) was
acid, m.p. 32±358. H-NMR d 1.25 (d, J = 3 Hz), 9.9 (s,
COOH); 13C-NMR d 185.8 (13COOH).
The labeled acid (0.4 g) in 100 ml of anhydrous ether was
treated 0.8 g of lithium aluminum hydride (white powder,
excess) at 08, and was allowed to stir overnight. The mixture
was acidi®ed with cold dilute HCl. The ether layers was
extracted with dilute NaHCO3, dried and concentrated
to give the oily 1-13C-2,2-dimethylpropanol (0.17 g).
1
obtained in 90% yield. H-NMR (CDCl3, TMS) d 2.95 (d
1H-NMR
d
0.89 (d, J = 1.8 Hz, CH3), 3.27 (d,
of t, CH2, JCH3 = 6.3 Hz, JCF = 24.0 Hz, 2H), 4.60 (d of t,
CH2F, JCH3 = 6.0 Hz, JCF = 47.1 Hz, 2H), 6.97±7.65 (m, Ar-
H, 5H); 19F-NMR (CDCl3, TFA) d 140.2 (m, CH2F); lit.
[14,15] d 140 (t, CH2F); ms 118 (M-HF), calc. 118 (M-
HF).
J = 140 Hz, 13CH2); 13C-NMR d 73.3 (13CH2OH).
The labeled alcohol (20 mg) and methyl triphenoxypho-
sphonium iodide were mixed in a 0.5 ml distilling vial and
heated mildly with a low ¯ame Bunsen burner. The vapors
were condensed in a Dry-Ice acetone cooled side arm
receiver tube to give 15 mg of 1-13C-1-iodo-2,2-dimethyl-
13
3.6. 2-Fluoro-1-phenylpropane (13)
propane (bf ꢀ C 1†). 1H-NMR d 0.93 (d, J = 2 Hz, CH3)
3.04 (d, J = 148 Hz, 13CH2); 13C-NMR d 25.76 (13CH2I).
The product contained 5% of 2-iodo-2-methyl-3-13C-
butane: 13C-NMR d 43.3 (13CH2CH3).
2-Phenyl-1-iodopropane (10, 0.5 mmol, 120 mg) was
placed in a 10 ml vial equipped with a re¯ux condenser.

T.B. Patrick et al. / Journal of Fluorine Chemistry 102 (2000) 11±15
15
4.2. Reaction of 1-13C-1-iodo-2,2-dimethylpropane with
XeF2
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13
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Funding for this research was provided by grants from the
National Science Foundation (RUI) and the Petroleum
Research Fund (Type B), administered by the American
Chemical Society.