The fluorous Swern and Corey-Kim reactions: Scope and mechanism

Article abstract of DOI:10.1016/S0040-4020(02)00207-7

Protocols for the efficient preparation of 1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluoro-8-methanesulfenyloctane and 1,1,1,2,2,3,3,4,4-nonafluoro-6-methanesulfenylhexane (fluorous dimethyl sulfide) and for their oxidation to the corresponding sulfoxides (fluorous dimethyl sulfoxide) are reported. The lower molecular weight sulfoxide, in conjunction with oxalyl chloride and Hunig's base, brings about the oxidation of diversely functionalized primary and secondary alcohols to aldehydes and ketones in excellent yield. The fluorous sulfoxide is efficiently recovered for reuse by a simple continuous fluorous extraction and hydrogen peroxide oxidation protocol. The whole process is odor-free. A deuterium-labeling experiment is used to demonstrate that the oxidations take place via the classical Swern mechanism, i.e. by intramolecular hydride abstraction from a sulfur ylid. Corey-Kim oxidations may be performed with the higher molecular weight fluorous sulfide, although recycling is not as efficient.

Full text of DOI:10.1016/S0040-4020(02)00207-7

TETRAHEDRON
Pergamon
Tetrahedron 58 ,2002) 3865±3870
The ¯uorous Swern and Corey±Kim reactions:
scope and mechanism
David Crichp and Santhosh Neelamkavil
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7061, USA
Received 29 October 2001; accepted 9 November 2001
AbstractÐProtocols for the ef®cient preparation of 1,1,1,2,2,3,3,4,4,5,5,6,6-trideca¯uoro-8-methanesulfenyloctane and 1,1,1,2,2,3,3,4,4-
nona¯uoro-6-methanesulfenylhexane ,¯uorous dimethyl sul®de) and for their oxidation to the corresponding sulfoxides ,¯uorous dimethyl
sulfoxide) are reported. The lower molecular weight sulfoxide, in conjunction with oxalyl chloride and Hunig's base, brings about the
oxidation of diversely functionalized primary and secondary alcohols to aldehydes and ketones in excellent yield. The ¯uorous sulfoxide is
ef®ciently recovered for reuse by a simple continuous ¯uorous extraction and hydrogen peroxide oxidation protocol. The whole process is
odor-free. A deuterium-labeling experiment is used to demonstrate that the oxidations take place via the classical Swern mechanism, i.e. by
intramolecular hydride abstraction from a sulfur ylid. Corey±Kim oxidations may be performed with the higher molecular weight ¯uorous
sul®de, although recycling is not as ef®cient. q 2002 Elsevier Science Ltd. All rights reserved.
Environmental and economic factors have combined in
recent years to force the development of cleaner, more
atom-economic, ef®cient chemistry.1 In this regard the
advent of ¯uorous chemistry, ®rst with recyclable, ¯uorous
catalysts,2 then with similarly recyclable ¯uorous reagents,3
and most recently with protocols for the coupling of
reactivity to ¯uorous separation,4 has been very timely.
The oxidation of alcohols is perhaps one of the most wide-
spread, both in the research laboratory and in the production
plant, but least environmentally friendly organic reactions
being largely metal-based with all the associated problems
of the expensive disposal of toxic waste streams. It is not
surprising therefore that methodology for the oxidation of
primary and secondary alcohols to aldehydes and ketones is
being continually re®ned and improved. The focus has been
largely on catalytic reactions, as typi®ed by Ley and
Grif®th's tetrapropylammonium perruthenate oxidant,5
especially the variants based on the use of oxygen as
oxidants,6 and the more recent palladium-catalyzed oxida-
tions that also make use of air as the stoichiometric reagent.7
Completely metal-free oxidations obviously also have much
potential for environmentally friendly processes, particu-
larly if the reagents can be readily recovered and recycled.
With this in mind we turned to the examination of possible
¯uorous, metal-free oxidation systems. The most common
metal-free systems for the oxidation of alcohols are the
tempo-catalyzed systems, employing bleach as stoichio-
metric oxidant,8 the Dess±Martin periodinane reagent9
and its more user-friendly version, 2-iodoxybenzoic
acid,10,11 and the Swern reaction and its numerous
variants.12,13 Among these the Swern reaction was the
most obvious choice for the development into a ¯uorous
based system for several reasons. First, with the stoichio-
metric generation of dimethyl sul®de, it falls down badly on
environmental grounds.14 Second, the low molecular weight
of dimethyl sulfoxide suggests that the introduction of only
a single, short per¯uoroalkyl chain should render it prefer-
entially soluble in ¯uorous solvents. This is important in
terms of economics, with the longer ¯uorous chains being
obviously more expensive, but also in terms of practicality,
especially as pertains to the need to maximize solubility.
Here, we present in full the successful development and
implementation of a ¯uorous Swern reagent, including the
demonstration of mechanism.15
In designing the ¯uorous Swern reagent our primary
concern was with the length of the spacer linking the
¯uorous chain to the sulfoxide. Reagents lacking a spacer,
i.e. with the ¯uorous chain directly bound to the sulfoxide
sulfur, were excluded from consideration as it was antici-
pated that they would reduce the nucleophilicity of the
sulfoxide and so reduce activity. Linkers consisting of
only one methylene group were tried and found wanting
on the basis of the facile elimination of HF from the
sulfoxide. Linkers with three or more methylene groups,
while undoubtedly effective, were eliminated from con-
sideration on the grounds that they would require a longer
¯uorous chain for ef®cient extraction. We therefore settled
on a two methylene group spacer and initially selected
per¯uorohexyl as the ¯uorous chain as this would lead to
a reagent with 60.2% ¯uorine, with 60% usually considered
the lower cutoff point for ef®cient ¯uorous extraction.16
Keywords: oxidation; ylids; sulfoxides; ¯uorine and compounds.
Corresponding author. Tel.: 11-312-996-5189; fax: 11-312-996-2183;
e-mail: dcrich@uic.edu
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020,02)00207-7

3866
D. Crich, S. Neelamkavil / Tetrahedron 58 +2002) 3865±3870
Scheme 1. Preparation of ¯uorous DMS and ¯uorous DMSO.
Reduction of dimethyl disul®de with sodium borohydride in
ethanol, followed by treatment with commercial 2-per-
¯uorohexylethyl iodide provided, after stirring overnight
and standard work up, the ¯uorous sul®de 1 in 74%
yield.17 Alternatively, dimethyl disul®de was reduced with
thiourea dioxide18 in the presence of the ¯uorous alkyl
iodide when the sul®de 1 was obtained in 85% yield.
These direct syntheses of 1 are considerable improvements
over an earlier multistep protocol, involving reaction of the
iodide with sodium thiocyanate, reduction and methyl-
ation.19 Oxidation of 1 with hydrogen peroxide in
methanol20 provided the sulfoxide 3 in high overall yield
with no overoxidation to the sulfone, it having been
previously determined that more forcing conditions are
required for the exhaustive oxidation of 1.19 Oxidation
with mCPBA was also ef®cacious, stopping cleanly at the
sulfoxide, and resulting in a 95% isolated yield of 3. Sulf-
oxide 3 was crystalline, white, and odorless but unfortu-
nately insoluble in dichloromethane below ,2308C. We
therefore prepared the lower homologous sul®de ,2) and
its sulfoxide ,4) in the analogous manner in 71% overall
yield from commercial per¯uorobutylethyl iodide.
,Scheme 1). Sulfoxide 4 is also crystalline, white, and
odorless but it is soluble in dichloromethane down to
2458C. It has a ¯uorine content of 55.1% and is recoverable
by continuous ¯uorous extraction, our preferred protocol,21
and no doubt, by chromatography over ¯uorous silica gel.22
The intermediate sul®de ,2), however, is relatively
volatile and in general we have converted it directly to
sulfoxide 4.
tion protocol. However, any residual sulfoxide is not readily
extracted from dichloromethane solution, presumably
because of its somewhat polar nature. Replacing dichloro-
methane by the apolar toluene reduces the af®nity of 4 for
the organic phase and enables the ef®cient recoveries
recorded in Table 1.
As is apparent from Table 1 the ¯uorous Swern reaction
retains the mildness of conditions and applicability in the
presence of a wide range of functional groups that have
contributed to the popularity of the original reaction. In
addition to the typical oxidations of primary and secondary
alcohols we note the compatibility with Lipshutz's new tri-
isopropylsiloxycarbonyl protecting group ,entry 2),24 the
absence of b-elimination of a tert-butyldimethylsiloxy
group ,entry 3), and the oxidation of lactols to lactones
,entries 11 and 12), again without b-elimination.
The mechanism of the ¯uorous Swern reaction was brie¯y
investigated through the oxidation of monodeuterioiso-
borneol. Thus, camphor was reduced with lithium
aluminum deuteride to give deuterioisoborneol, which was
then subjected to oxidation with 3 in the normal manner.
The reaction mixture was subjected to a standard aqueous
work-up and the ¯uorous sul®de 1 was recovered by silica
1
gel chromatography. Examination of this substance by H
NMR spectroscopy revealed a diminution in the intensity of
the S-methylene, group as well as a change in the coupling
pattern of the RF-methylene group, consistent with the
incorporation of a deuterium atom into the S-methylene
2
group. This was con®rmed by the H NMR spectrum of
A series of oxidations were conducted in which ¯uorous
DMSO ,4) was activated with oxalyl chloride in dichloro-
methane at 2308C and subsequently treated with the
substrate and then diisopropylethylamine almost as in the
standard Swern oxidation. The practicality of the classical
Swern protocol is therefore retained. Work-up involved
brief partitioning of the reaction mixture with water,
concentration of the dichloromethane solution and partition-
ing of the residue between toluene and FC72 ,a commercial
¯uorous hydrocarbon) in the continuous extractor for
<4 h.21 The oxidized product ,aldehyde or ketone) was
then recovered from the toluene phase, while treatment of
the FC72 phase with hydrogen peroxide returned the sulf-
oxide ready for reuse.23 The results of these oxidations,
together with the yields of recovered sulfoxide, are
presented in Table 1.
the recovered sul®de, which exhibited a unique signal at d
2.86. The reactions described here therefore fall into the
category of true Swern oxidations and proceed via a sulfur
ylid with subsequent intramolecular hydrogen transfer
,Scheme 2).25 The highly regioselective deprotonation,
from the S-methylene rather than the S-methyl group, nicely
illustrates the strongly electron-withdrawing nature of the
¯uorous chain and its effect on acidity of neighboring C±H
bonds.
In addition to the Swern oxidation we have brie¯y investi-
gated a ¯uorous version of the Corey±Kim reaction.26 This
system employs the sul®de and not the sulfoxide and hence
it was possible to work with the higher homolog ,1), taking
advantage of its convenient, less volatile nature. Several
examples of the successful use of this protocol are given
in Table 2. However, it is important to note that in order to
obtain the high recoveries of ¯uorous sul®de it was
necessary to work with as near stoichiometric sul®de as
possible. This is because any excess sul®de is oxidized by
the excess NCS and is not recoverable, at least in the form of
the sul®de.
An important practical consideration in these oxidations is
the exchange of dichloromethane, the reaction solvent, for
toluene before the ¯uorous extraction. At this stage most of
the sulfoxide ,4) has been reduced to the sul®de 2, which,
itself, is very non-polar and readily recovered in the extrac-

D. Crich, S. Neelamkavil / Tetrahedron 58 +2002) 3865±3870
3867
Table 1. Fluorous Swern oxidations
Entry
1
Substrate
Product
,% Yield)
6 ,92)
% Recd 4
87
2
3
8 ,77)
84
88
10 ,91)
4
5
6
12 ,91)
14 ,90)
16 ,94)
86
89
90
7
18 ,83)
86
8
21 ,81)
23 ,81)
86
84
9a
10
11
25 ,80)
88
27 ,79)
29 ,86)
85
87
12
a
DAMˆdianisylmethyl.
Scheme 2. Incorporation of deuterium from deuterioisoborneol into sul®de 1.

3868
D. Crich, S. Neelamkavil / Tetrahedron 58 +2002) 3865±3870
Table 2. Fluorous Corey±Kim oxidations
Entry
1
Substrate
Product
,% Yield)
6 ,83)
% Recd 4
76
2
3
12 ,86)
14 ,78)
73
73
4
5
16 ,88)
32 ,88)
72
75
In conclusion, an ef®cient protocol for the preparation and
application of a ¯uorous Swern reagent has been developed.
A wide range of primary and secondary alcohols may be
oxidized to the corresponding aldehydes and ketones in high
yield, under completely odor free reactions. The ¯uorous
reagent is recovered for reuse through a simple continuous
¯uorous extraction and reoxidation with hydrogen peroxide.
was added. After stirring for 6 h more, the reaction mixture
was diluted with hexanes ,20 mL) and washed with H2O and
brine. The hexane layer containing the sul®de 2 was diluted
with MeOH ,10 mL) and H2O2 ,3.1 mL of 30%, 27 mmol)
and stirred for 1 h before it was diluted with CH2Cl2
,25 mL), washed with H2O, dried ,Na2SO4) and concen-
trated in vacuo to give 4 ,5.9 g, 19.0 mmol, 71%) as a
white, crystalline solid with mp 468C.
1. Experimental
1.1. General
1.3. Alternative protocol for the formation of ¯uorous
sul®des by thiourea sulfur dioxide reduction of dimethyl
disul®de
All reagents were purchased from commercial sources and
used as received, unless otherwise indicated. Tetrahydro-
furan and benzene were distilled from sodium/benzo-
phenone ketyl and methylene chloride was distilled from
To a mixture of per¯uorohexylethyl iodide ,1.0 g, 2 mmol),
Me2S2 ,0.094 g, 1 mmol), thiourea dioxide ,0.11 g,
1 mmol), and cetyltrimethylammonium bromide ,20 mg,
0.05 mmol) in THF ,8 mL) under argon was added 6%
aqueous NaOH ,8 mL), followed by heating to re¯ux for
4±5 h. After cooling to room temperature, the organic
layer was separated and the aqueous layer washed with
ethyl acetate. Concentration of the extracts and ¯ash chro-
matography on silica gel eluting with hexanes yielded pure
¯uorous sul®de 1 ,0.67 g, 85%).
calcium hydride prior to use. H, H, 13C and 19F NMR
spectra were recorded in deuteriochloroform solutions at
500 or 300, 77, 125 or 75, and 282 MHz, respectively.
Elemental analyses were performed by Midwest Microlabs,
Indianapolis, IN. All the reactions were run under a dry
argon atmosphere unless and otherwise stated. With the
exception of 7, described below, oxidation substrates were
either commercial or were prepared as described in the
literature ,9,27 13,28 20,29 22,30 26,31 2832). With the excep-
tion of 8, described below, oxidation products were identical
to either commercial or literature ,6,33 10,27 14,28 18,34 21,29
23,35 25,36 27,31 2932) samples.
1
2
1.4. Alternative protocol for the oxidation of ¯uorous
sul®des to sulfoxides with mCPBA
To the ¯uorous sul®de 1 ,0.25 g, 0.6 mmol) dissolved in
dichloromethane ,5 mL) at 2788C was added mCPBA
,0.14 g, 77%, 0.6 mmol) portionwise. The reaction mixture
was allowed to warm to 08C and was then stirred for a
further 10 min before it was quenched by addition of sat.
aqueous NaHCO3. The organic layer was washed further
with water and brine and the solvents evaporated to give
pure crystalline 3 ,0.25 g, 95%).
1.2. Protocol for the preparation of ¯uorous sul®des and
sulfoxides by borohydride reduction of dimethyl
disul®de and hydrogen peroxide oxidation
NaBH4 ,1.4 g, 37.0 mmol) was added under Ar to a stirred
solution of Me2S2 ,3.3 g, 35.0 mmol) in EtOH ,25 mL).
After stirring for 30 min the reaction mixture was cooled
to 08C and a solution of per¯uorobutylethyl iodide ,10 g,
26.7 mmol) in anhydrous THF ,15 mL) was added dropwise
over 1 h. The reaction mixture was then stirred overnight at
room temperature before further Me2S2 ,1.0 g, 10.6 mmol)
reduced with NaBH4 ,0.45 g, 11.9 mmol) in EtOH ,10 mL)
1.5. Fluorous sul®des and sulfoxides
1.5.1. 1,1,1,2,2,3,3,4,4,5,5,6,6-Trideca¯uoro-8-methane-
sulfenyloctane 21). H NMR: d 2.76±2.73 ,m, 2H); 2.47±
1
2.36 ,m, 2H); 2.18 ,s, 3H); 13C NMR: d 119.9±108.7 ,m),
32.3 ,t), 25.1 ,s), 15.9 ,s); 19F NMR: d 253.8, 251.0 ,d),

D. Crich, S. Neelamkavil / Tetrahedron 58 +2002) 3865±3870
3869
250.5, 249.5, 242.0 ,m), 28.5 ,t). Anal. calcd for
C9H7F13S: C, 27.42, H, 1.79; Found: C, 27.45, H, 1.72.
for a period of 30 min before it was quenched with H2O,
washed with ammonium chloride ,5 mL), extracted with
CH2Cl2 ,10 mL) and carefully concentrated under aspirator
vacuum in a cold water bath. The reaction mixture was then
dissolved in toluene ,6 mL) and extracted continuously with
FC 72 ,15 mL) in a cooled continuous extractor21 for 4 h.
After decantation, concentration of the toluene layer and
chromatography on silica gel yielded camphor ,0.142 g,
94%). The FC-72 phase, containing a mixture of 2 and 4,
was then stirred with MeOH ,3 mL) and H2O2 ,0.23 mL of
30%, 2 mmol) for 1 h after which it was diluted with H2O
,5 mL), and extracted with CH2Cl2 ,10 mL) in a three phase
system. Concentration of the CH2Cl2 layer then gave recov-
ered 4 ,0.9 g, 90%).
1.5.2.
1,1,1,2,2,3,3,4,4-Nona¯uoro-6-methanesulfenyl-
hexane 22).19 1H NMR: d 2.76±2.73 ,m, 2H); 2.47±2.36
,m, 2H); 2.18 ,s, 3H); 13C NMR: d 117.1±108.2 ,m), 32.1
,t), 25.0 ,s), 15.9 ,s); 19F NMR: d 253.7 ,t), 252.0 ,d),
242.2 ,t), 28.7 ,t).
1.5.3. 1,1,1,2,2,3,3,4,4,5,5,6,6-Trideca¯uoro-8-methane-
sul®nyloctane 23). Mp 648C; H NMR: d 3.04±2.98 ,m,
1
1H); 2.92±2.86 ,m, 1H); 2.72±2.61 ,m, including a s at
2.68, 5H); 13C NMR: d 133.3±128.4 ,m), 118.8±111.1
,m), 45.1 ,s), 39.3 ,s), 25.1 ,t); 19F NMR: d 28.4 ,d),
241.1, 249.4, 250.5, 250.8, 253.7 ,d). Anal. calcd for
C9H7F13SO: C, 26.35, H, 1.72; Found: C, 26.29, H, 1.71.
1.7.1. O-Triisopropylsilyl N-allyl-N-24-oxobutyl)carba-
1
mate 28). H NMR d 9.68 ,t, Jˆ1.3 Hz, 1H), 5.78± 5.61
1.5.4.
1,1,1,2,2,3,3,4,4-Nona¯uoro-6-methanesul®nyl-
,m, 1H), 5.03 ,br, d, Jˆ12 Hz, 2H), 3.74 ,br, s, 2H), 3.13 ,t,
Jˆ6.3 Hz, 2H), 2.37 ,t, Jˆ7.2 Hz, 2H), 1.75 ,quintet,
Jˆ7.2 Hz, 2H), 1.36 ,s, 9H); 13C NMR d 201.8, 155.2,
134.1, 116.6, 116.4, 116.3, 79.7, 49.8, 49.3, 45.7, 45.6,
41.1, 28.5, 23.6, 20.8. Anal. calcd for C12H21NO3: C,
63.41; H, 9.31. Found: C, 63.16; H, 9.19.
1
hexane 24). Mp 468C; H NMR: d 3.04±2.98 ,m, 1H);
2.92±2.86 ,m, 1H); 2.72±2.61 ,m, including a s at 2.68,
5H); 13C NMR: d 133.3±128.4 ,m), 118.8±108.6 ,m),
45.1 ,s), 39.3 ,s), 25.0 ,t); 19F NMR: d 28.5 ,t), 241.3
,m), 251.7 ,d), 253.6 ,t). Anal. calcd for C7H7F9SO: C,
27.11, H, 2.27; Found: C, 27.44, H, 2.44.
1.8. 2-Deuterioisoborneol38
1.6. O-Triisopropylsilyl N-allyl-N-4-hydroxybutyl)-
carbamate 27)
To a slurry of LiAlD4 ,0.012 g) in anhydrous ether ,1 mL)
was added with stirring camphor ,0.1 g) in ether ,2 mL)
followed by heating to re¯ux for 3 h. After cooling to
room temperature the excess hydride was decomposed by
addition of moist ether then the organic layer was washed
with brine, dried ,Na2SO4) and evaporated to give a quanti-
tative yield of deuteriated isoborneol ,0.1 g). 2H NMR
,hexanes): d 3.75.
To
a
solution of 4-allylaminobutan-1-ol37 ,1.06 g,
8.27 mmol) in CH2Cl2 ,30 mL) was added Et3N ,5.6 mL,
20.6 mmol) followed by cooling to 2788C and the bubbling
of dry CO2 for 2.5 h. TIPSOTf ,2.6 mL, 9.9 mmol) was then
added dropwise at 2788C and stirring continued at that
temperature for 1.5 h before the solution was gradually
warmed to room temperature and stirred for 2 h. The reac-
tion mixture was then diluted with H2O ,50 mL) and the
aqueous layer was extracted with CH2Cl2 ,3£70 mL). The
combined organic layers were washed with saturated
aqueous NaHCO3 ,3£50 mL), H2O ,2£50 mL) and brine
,2£50 mL), dried ,Na2S04) and concentrated under reduced
pressure. Puri®cation by column chromatography on silica
gel ,hexanes/ethyl acetate 3:1 then gave the title compound
1.9. Fluorous oxidation of deuterioisoborneol
The ¯uorous oxidation was performed with sulfoxide 3 by
the standard protocol with the exception of the work up and
isolation. When the oxidation was complete ,TLC) the reac-
tion was quenched with saturated aqueous NH4Cl and the
organic layer carefully concentrated. The residue was then
deposited on a short silica gel column, which was eluted
with hexanes. Evaporation of the eluent gave the deuteriated
1
,2.53 g, 93%) as a colorless oil. H NMR ,508C) d 5.83±
5.73 ,m, 1H), 5.16±5.09 ,m, 2H), 3.86 ,d, Jˆ5.7 Hz, 2H),
3.63 ,t, Jˆ6 Hz, 2H), 3.26 ,t, Jˆ7.5 Hz, 2H), 1.68±1.48 ,m,
4H), 1.36±1.23 ,m, Jˆ7.2 Hz, 3H), 1.08 ,d, Jˆ7.2 Hz,
18H); 13C NMR d 155.1, 134.2, 116.2, 62.5, 50.3, 49.7,
47.3, 46.7, 30.1, 29.8, 25.1, 24.5, 17.9, 17.5, 12.7, 12.2.
Anal. calcd for C17H35NO3Si: C, 61.96; H, 10.70. Found:
C, 62.20; H, 10.82.
2
¯uorous sul®de 1. H NMR ,hexanes): d 2.86.
1.10. General procedure for Corey±Kim oxidation with
¯uorous sul®de 1
To a solution of N-chlorosuccinimide ,0.1 g, 0.8 mmol) in
toluene ,2 mL) was added 1 ,0.4 g, 1 mmol) at 08C
resulting in the immediate formation of a white cloudy
precipitate. The reaction mixture was cooled to 2258C
and a solution of octanol ,0.07 g, 0.5 mmol) in toluene
,2 mL) was added. After stirring at 2258C for 2 h a solution
of Et3N ,0.08 g, 0.8 mmol) was added. The cold bath was
removed after 5 min and the reaction mixture washed with
sat. aqueous NH4Cl, then water. The organic layer was
extracted continuously with FC 72 ,15 mL) in a cooled
continuous extractor for a period of 4 h. Concentration of
the toluene layer and chromatography on silica gel
,eluent: EtOAc/hexanes 3:1) yielded octanal ,0.06 g,
88%). The FC-72 layer was carefully concentrated under
1.7. Typical protocol for oxidation with 4 and its
recovery
To a well stirred solution of anhydrous CH2Cl2 ,5 mL)
under Ar at 2308C was added oxalyl chloride ,0.14 mL,
1.6 mmol). A solution of sulfoxide 4 ,1.0 g, 3.2 mmol) in
CH2Cl2 ,3 mL) was then added dropwise and the reaction
mixture stirred for an additional 20 min. Isoborneol
,0.153 g, 1.0 mmol) dissolved in CH2Cl2 ,5 mL) was then
added to this solution followed, after an additional 0.5±1 h,
by EtN,i-Pr)2 ,0.88 mL, 5.0 mmol). The reaction mixture
was then allowed to warm to room temperature and stirred

3870
D. Crich, S. Neelamkavil / Tetrahedron 58 +2002) 3865±3870
been previously addressed by the Vederas group who have
introduced polymer-supported and extractable non-volatile
reagents. ,a) Harris, J. M.; Liu, Y.; Chai, S.; Andrews,
M. D.; Vederas, J. C. J. Org. Chem. 1998, 63, 2407. ,b) Liu,
Y.; Vederas, J. C. J. Org. Chem. 1996, 61, 7856.
15. Preliminary communication: Crich, D.; Neelamkavil, S.
J. Am. Chem. Soc. 2001, 123, 7449.
aspirator vacuum to give the recovered ¯uorous sul®de 1
,0.3 g, 75%).
Acknowledgements
We thank the NSF ,CHE 9986200) for support of this work
and Krishnakumar Ranganathan for the preparation of
alcohol 7.
16. Ogawa, A.; Curran, D. P. J. Org. Chem. 1997, 62, 450.
17. Sul®des have been previously reported to displace ¯uoride
from per¯uorodecalin: MacNicol, D. D.; Robertson, C. D.
Nature 1988, 332, 59. No evidence was found for the displa-
cement of ¯uoride in either of the preparations of 1 and 2
reported here.
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