Unexpected formation of 10-iodo- and 10-chlorocamphor under halosulfonylation conditions, and convenient routes to 10-chloro- and 10-bromocamphor

Article abstract of DOI:10.1016/j.tetasy.2009.05.012

The generation of camphor-10-sulfonyl iodide in situ under halosulfonylation conditions or exposure of camphor-10-sulfonyl chloride to copper(II) chloride under Asscher-Vofsi conditions leads unexpectedly to the formation of 10-iodocamphor or 10-chlorocamphor, respectively. Additionally, convenient syntheses of 10-bromocamphor and 10-chlorocamphor have been achieved by extension of a previously reported methodology.

Full text of DOI:10.1016/j.tetasy.2009.05.012

Tetrahedron: Asymmetry 20 (2009) 1531–1535
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Tetrahedron: Asymmetry
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Unexpected formation of 10-iodo- and 10-chlorocamphor under
halosulfonylation conditions, and convenient routes to 10-chloro- and
10-bromocamphor
Frank W. Lewis, Gilles Egron, David H. Grayson *
Centre for Synthesis and Chemical Biology, University Chemical Laboratory, Trinity College, Dublin 2, Ireland
a r t i c l e i n f o
a b s t r a c t
Article history:
The generation of camphor-10-sulfonyl iodide in situ under halosulfonylation conditions or exposure of
camphor-10-sulfonyl chloride to copper(II) chloride under Asscher–Vofsi conditions leads unexpectedly
to the formation of 10-iodocamphor or 10-chlorocamphor, respectively. Additionally, convenient synthe-
ses of 10-bromocamphor and 10-chlorocamphor have been achieved by extension of a previously
reported methodology.
Received 6 May 2009
Accepted 12 May 2009
Available online 8 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1
. Introduction
Unsaturated sulfones have found widespread use as versatile
R
R*SO2
R* =
intermediates in organic synthesis, especially as Michael acceptors
and in cycloaddition reactions.1 However, there do not appear to
have been any reports of either the synthesis or applications of
,2
O
1
2
*
vinylic sulfones 1, which possess homochiral alkyl groups R that
are directly attached to the sulfur atom. The conformationally ri-
gid, monoterpenoid-based camphorsulfonyl framework 2 (Fig. 1),
which is already widely exploited as a component of various prac-
3
X = Cl
4 X = Br
5 X = I
O
3
tical chiral auxiliaries, and which is readily available in both enan-
X
tiomeric forms, seemed to be a promising candidate for this
purpose. Herein we report the unexpected formation of 10-halo-
camphors 3–5 (X = Cl/Br/I) during attempted halosulfonylation
reactions of some alkenes, and show how these versatile chiral
synthons can be readily accessed from (+)-camphor-10-sulfonic
acid.
Figure 1. Homochiral camphor-based vinyl sulfones and the 10-halocamphors.
When an aqueous solution of sodium (+)-camphor-10-sulfinate 6
was vigorously stirred at ambient temperature with a DCM solution
of iodine and allyl benzyl ether, (À)-10-iodocamphor 5 was formed
unexpectedly and unchanged alkene was recovered, rather than the
expected b-iodosulfone (Scheme 1). (À)-10-Iodocamphor 5 was also
obtained in the absence of the alkene, and when triethylamine (nor-
mally used to generate the vinyl sulfone in situ from the b-iodosulf-
one) was added before work-up. On the other hand, when either
norbornene or 1,5-cyclooctadiene was the alkene, reaction with so-
dium (+)-camphorsulfinate 6 and iodine in methanol as solvent, fol-
2
. Results and discussion
During the course of our ongoing work on the development of
sulfonyl-based chiral auxiliaries, we sought to synthesise various
chiral vinyl sulfones via halosulfonylation reactions of alkenes. Ini-
tially, we opted to generate camphor-10-sulfonyl iodide 7 in situ in
the presence of an alkene, by treating sodium (+)-camphor-10-
sulfinate 6 (available by reduction of (+)-camphor-10-sulfonyl
lowed by in situ treatment with potassium tert-butoxide did afford
the expected vinylic sulfones, albeit in only modest yields.6
4
chloride) with iodine, a strategy successfully utilised by others
We next showed that the reaction of sodium (+)-camphor-10-
sulfinate 6 with bromine in DCM solution formed the sulfonyl bro-
mide 8, which could be converted into (+)-10-bromocamphor 4.
This required the thermolysis of crude 8 in either refluxing xylene
or toluene, demonstrating its greater stability over that of sulfonyl
iodide 7.
for reactions involving arenesulfonyl iodides.5
*
Corresponding author. Tel.: +353 1896 2021; fax: +353 1671 2826.
E-mail addresses: dgrayson@tcd.ie, flewis@tcd.ie (D.H. Grayson).
0
957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.05.012

1
532
F. W. Lewis et al. / Tetrahedron: Asymmetry 20 (2009) 1531–1535
I2 or Br2
- SO2
O
DCM
1.5h
O
SO2X
O
SO2Na
X
6
7 X = I
5 X = I
4 X = Br
8
X = Br
Scheme 1.
These results prompted us to investigate the addition of (+)-
camphor-10-sulfonyl chloride 9 to alkenes under free-radical con-
ditions. Asscher and Vofsi have described how the radical addition
(+)-10-chlorocamphor 3, respectively (Scheme 3). The failure of the
sulfonyl halides 7 and 9 to form adducts with alkenes is perhaps
not too surprising, given that analogous aliphatic alkanesulfonyl
iodides are unstable and decompose with the loss of sulfur
of arenesulfonyl chlorides to alkenes can be conveniently catalysed
7
9
by the system CuCl
2
–Et
3
NÁHCl in refluxing toluene. However,
dioxide.
when 1,5-cyclooctadiene was reacted with (+)-camphor-10-sulfo-
nyl chloride 9 under these conditions, none of the anticipated ad-
duct was formed. Instead, the alkene was recovered and (+)-10-
chlorocamphor 3 was obtained in excellent yield (Scheme 2). The
same product 3 was efficiently formed in the absence of alkene,
but it was not obtained in the absence of the Cu(II) catalyst. Other
simple cycloalkenes, such as cyclohexene, also failed to yield radi-
cal addition products under Asscher–Vofsi conditions.
The 10-halocamphors 3, 4 and 5 have been widely used both as
sources of chirality in asymmetric synthesis, and as precursors to
chiral synthons employed in total synthesis. Both (+)-10-bromo-
camphor 4 and (À)-10-iodocamphor 5 have been converted into
various homochiral bidentate P–P, N–P and N–S donor ligands for
1
0
11
asymmetric synthesis. Chiral imidazolium-based ionic liquids,
1
2
telluronium salts and ligands for asymmetric Pauson-Khand
1
3
reactions have been derived from (À)-10-iodocamphor 5, whilst
chiral Brönsted acids have been synthesised from (+)-10-bromo-
1
4
camphor 4. Additionally, fragmentation of the C(1)–C(2) bond
in 4 and 5 affords chiral cyclopentenes which have been utilised
CuCl2
15
Et NHCl
3
as chiral synthons in the total synthesis of various natural
1
6
products.
+)-10-Chlorocamphor 3 has previously been obtained from
(
PhMe
reflux, 4h
O
O
17
18
‘
oxy-camphene’; by the oxidation of 10-chloroisoborneol; by
SO Cl
Cl
2
the reduction of 8-bromo-3,10-dichlorocamphor using zinc in ace-
1
9
9
3
tic acid; by triflic anhydride-promoted Wagner–Meerwein rear-
2
0
rangement of (+)-camphor; and by prolonged reaction of (+)-
2
1
Scheme 2.
1
0-bromocamphor 4 with LiCl in DMF. Although the facile and
direct route to (+)-10-chlorocamphor 3 from (+)-camphor-10-sul-
fonyl chloride 9 via the method described above makes this a more
readily accessible chiral synthon, more efficient routes exist for the
preparation of (+)-10-bromocamphor 4 and (À)-10-iodocamphor 5
which can both be accessed from (+)-camphor in three steps via
From the above-mentioned results, we can conclude that homo-
lytic fission of the sulfonyl halides 7 and 9 leads to the rather hin-
dered, neopentyl-like, sulfonyl radical 10 which loses sulfur
dioxide to form the 10-camphoryl radical 11 more rapidly than
it can react with an alkene. Recombination of 11 with either an io-
dine or chlorine atom then yields either (À)-10-iodocamphor 5 or
8
20
the aforementioned Wagner–Meerwein rearrangement or, in
the case of (+)-10-bromocamphor 4, by thermolysis of (+)-cam-
2
2
phor-10-sulfonyl bromide 8.
A convenient synthesis of (À)-10-iodocamphor 5 directly from
commercially available (+)-camphor-10-sulfonic acid via reduction
2
3
2 3
with I /PPh has been previously reported, although to the best of
our knowledge this methodology has not been previously applied
to the synthesis of either 3 or 4. Given the widespread use of the
+
X
O
O
1
0-halocamphors 3, 4 and 5 as chiral synthons, we sought to ex-
SO2X
X = I
SO2
10
tend this methodology to the synthesis of both (+)-10-bromocam-
phor 4 and (+)-10-chlorocamphor 3 by the appropriate choice of
electrophilic halogenating reagent. These results are summarised
in Table 1.
7
9
X = Cl
-
SO2
Reduction of (+)-camphor-10-sulfonic acid 12 with bromine
(
3 equiv) and triphenylphosphine (5 equiv) in refluxing toluene
gave (+)-10-bromocamphor 4 in 78% yield after purification by
chromatography. Encouraged by this result, we examined various
halogen donors and found that both carbon tetrabromide and N-
bromosuccinimide were also suitable reagents for the preparation
of 4.
X
O
O
X
X = I
Similarly, carbon tetrachloride, hexachloroethane and N-chloro-
succinimide could all be successfully employed for the synthesis of
5
3
11
X = Cl
(
+)-10-chlorocamphor 3. However, in a number of the reduction
2
4
Scheme 3.
experiments bis(10-camphoryl) disulfide 13 was also obtained

F. W. Lewis et al. / Tetrahedron: Asymmetry 20 (2009) 1531–1535
1533
Table 1
3
Synthesis of 4 and 3 via reduction of (+)-camphor-10-sulfonic acid 12 with PPh and
various halogenating reagents
Entry Reagent
equiv)
PPh
(equiv)
3
Bu
(equiv)
3
N
Ratio of 3 or Yield of 3 or Yield of
14
15
a
b
b
(
4:13
4
(%)
13 (%)
O
1:0c
1.5:1
78 4
44 4
50 4
84 4
68 3
70 3
66 3
68 3
72 3
69 3
81 3
0
30
27
0
18
17
20
15
11
13
3
+
1
2
3
4
5
6
7
8
9
0
1
Br (3)
NBS (3)
2
(5)
(5)
(5)
(6)
(5)
(5)
(5)
(5)
(6)
(7)
(6)
(0)
(0)
(0)
(1)
(0)
(0)
(0)
(0)
(0)
(0)
(1)
S
+
PPh
3
CBr
CBr
4
(3)
(4)
(3)
1.9:1
+
PPh3
1:0c
4
C
2
Cl
6
3.4:1
3.7:1
O
O
NCS (3)
S
S
CCl
4
CCl
4
CCl
4
CCl
4
CCl
4
(3)
(3)
(4)
(5)
(4)
3:1
4.1:1d
13
6.2:1
5.8:1
30:1
O
1
1
SH
a
Determined by 1H NMR.
Isolated yield.
Disulfide 13 not detected.
Reaction time was 48 h.
Scheme 5.
b
c
d
these important chiral synthons directly from commercially avail-
able (+)-camphor-10-sulfonic acid 12.
in variable quantities as by-product in addition to the desired 10-
halocamphor 3 or 4 (Scheme 4).
4
4
. Experimental
By consideration of the mechanism of the analogous reduction
.1. General
23
of acid 12 with I
2 3
/PPh ,
we attribute the formation of disulfide
1
3 to the competitive trapping of the mercaptotriphenylphospho-
NMR spectra were recorded using a Bruker AVANCE DPX
00 MHz spectrometer (400.1 MHz for H and 100.6 MHz for
C). Chemical shifts are reported in parts per million. Coupling
constants (J) are quoted in hertz. Optical rotations were measured
using a Perkin–Elmer 141 polarimeter. IR spectra were recorded for
Nujol mulls (N) on a Mattson Genesis II FTIR spectrometer. Mass
spectra were obtained under electrospray conditions using a
Micromass LCT instrument. All solvents and reagents were purified
by standard techniques. Organic extracts of reaction products were
dried over anhydrous magnesium sulfate.
25
1
nium ion 14 with 10-mercaptocamphor 15, rather than with
the bromide ion or the somewhat less nucleophilic chloride ion
4
1
3
(Scheme 5). In order to minimise the formation of disulfide 13
and improve the yields of the desired 10-halocamphor 3 or 4, we
briefly examined the influence of reaction stoichiometry, reaction
time and the addition of base on the yields of 3 and 4.
It was found that by prolonging the reaction time (entry 8), or
the use of additional equivalents of both the halogenating reagent
and triphenylphosphine (entries 9 and 10) led to only a modest
improvement in the yield of 3. The best results were obtained
when tributylamine (1 equivalent) was added to the reaction mix-
4
.2. (1S,4R)-(7,7-Dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)
methanesulfonyl chloride 9
2
3
ture prior to reflux. Under these conditions, (+)-10-chlorocam-
phor 3 and (+)-10-bromocamphor 4 were obtained in improved
yields of 81% (entry 11) and 84% (entry 4), respectively.
Thionyl chloride (37.7 mL, 516 mmol) was added to (+)-cam-
phor-10-sulfonic acid 12 (40.0 g, 172 mmol) in a 1 L flask. The mix-
ture was stirred at room temperature for 1 h, warmed at 40 °C for a
further 6 h and then cooled back to room temperature and left stir-
ring overnight. The mixture was diluted with ether (400 mL) and
3
. Conclusion
It has been found that camphor-10-sulfonyl iodide 7, formed
in situ from sodium (+)-camphor-10-sulfinate 6, undergoes spon-
taneous and efficient conversion into (À)-10-iodocamphor 5. Sim-
ilarly, exposure of (+)-camphor-10-sulfonyl chloride 9 to Asscher–
Vofsi radical conditions generates (+)-10-chlorocamphor 3 in high
yield. Failure to effect the halosulfonylation of alkenes under these
conditions may be attributed to the competing rapid extrusion of
sulfur dioxide from the sterically hindered camphorsulfonyl radical
2
quenched over ice/H O. The aqueous layer was extracted with
ether (400 mL). The combined organic extracts were washed with
water (200 mL) and saturated sodium hydrogen carbonate solution
(4 Â 100 mL) until the evolution of CO
2
had ceased, and then dried
and evaporated to afford (+)-camphor-10-sulfonyl chloride 9 as a
26
white solid (38.0 g, 89%); mp 62–63 °C (ether); lit.: 67–68 °C.
2
7
[a
]
D
3 3
= +30.9 (c 1.29, CHCl , 27 °C); lit.: +28.8 (c 4.2, CHCl ). IR:
1
0. In addition, a previously reported synthesis of (À)-10-iodocam-
m
max (N) 2921, 1741 (C@O), 1459, 1368, 1279, 1171, 1132, 1102,
À1
1
phor 5 has been extended to deliver both (+)-10-chlorocamphor 3
and (+)-10-bromocamphor 4, leading to convenient syntheses of
1045 (SO
1.16 (s, 3H, 7-CH
2
), 854, 768 cm
.
3 3
H NMR (CDCl ): 0.94 (s, 3H, 7-CH ),
3
), 1.47–1.54 (m, 1H), 1.76–1.83 (m, 1H), 2.01 (d,
halogenating
reagent
+
PPh3
O
O
O
O
PhMe
SO3H
X
S
S
reflux, 24h
1
2
4 X = Br
X = Cl
13
3
Scheme 4.

1
534
F. W. Lewis et al. / Tetrahedron: Asymmetry 20 (2009) 1531–1535
J = 18.4, 1H, 3-CH
CH), 2.42–2.52 (m, 2H), 3.74 (d, J = 14.3, 1H, CH
2
endo), 2.08–2.16 (m, 1H), 2.18 (t, J = 4.7, 1H, 4-
SO Cl), 4.32 (d,
): 19.2 (7-CH ), 19.3 (7-
), 24.8 (C-5), 26.4 (C-6), 41.8 (C-3), 42.3 (C-4), 47.7 (C-7), 59.2
C-1), 63.7 (CH SO Cl), 212.3 (C-2).
water (50 mL) was then added and the mixture was extracted with
2
2
ether (3 Â 50 mL). The combined organic extracts were dried and
evaporated to yield an oil which was purified by column chroma-
tography on silica gel, eluting with ether/hexane (1:10) to afford
(+)-10-bromocamphor 4 as a white solid (0.33 g, 72%).
1
3
J = 14.3, 1H, CH
CH
2
SO
2
Cl). C NMR (CDCl
3
3
3
(
2
2
4
.3. Sodium (1S,4R)-(7,7-dimethyl-2-oxobicyclo[2.2.1]-hept-1-
4.5.2. Method B: from sulfonic acid 12
yl)methanesulfinate 6
(+)-Camphor-10-sulfonic acid 12 (1.00 g, 4.30 mmol) and tri-
phenylphosphine (6.77 g, 25.82 mmol) were dissolved in dry tolu-
ene (30 mL) under an atmosphere of nitrogen. Solid carbon
tetrabromide (5.71 g, 17.21 mmol) was added, followed by tribu-
tylamine (1.02 mL, 4.30 mmol) and the solution was heated at re-
flux for 24 h. The solution was then allowed to cool to room
temperature and water (50 mL) was added. The phases were mixed
and separated and the aqueous phase was extracted with DCM
(2 Â 50 mL). The combined organic extracts were washed with
water (50 mL), dried and evaporated to afford a brown solid
(12.59 g) which was triturated with ether (ca. 20 mL) and filtered.
The filtrate was evaporated to yield a brown solid which was puri-
fied by column chromatography on silica gel, eluting with ether/
hexane (1:10) to afford (+)-10-bromocamphor 4 as a white solid
(
+)-Camphor-10-sulfonyl chloride 9 (36.3 g, 144 mmol) in dry
acetone (80 mL) was added dropwise over 4 h to a solution of so-
dium sulfite (35.29 g, 280 mmol) and sodium hydrogen carbonate
(
23.52 g, 280 mmol) in water (200 mL) maintained at 70 °C. The
mixture was stirred for an additional 1 h at 70 °C and then allowed
to cool to room temperature and left stirring overnight. The mix-
ture was evaporated to yield a white residue which was taken up
in boiling methanol (ca. 100 mL) and filtered through Celite. The
filtrate was evaporated to afford sodium sulfinate 6 as a white solid
1
(
31.43 g, 94%) together with ca. 5% ( H NMR) of the corresponding
sodium sulfonate. This was used without further purification;
26
[
1
1
(
(
2
a
]
D
= À41.8 (c 0.76, H
9 °C). IR: max (N) 3358, 2918, 1741 (C@O), 1460, 1375, 1278,
197, 1020, 973, (S@O), 851, 816, 723 cm
), 0.93 (s, 3H, 7-CH ), 1.33–1.40 (m, 1H), 1.43–1.51
m, 1H), 1.88 (d, J = 19.0, 1H, 3-CH endo), 1.92–2.00 (m, 1H),
.00–2.06 (dd, J = 12.0, 2.5, 1H), 2.10 (t, J = 4.5, 1H, 4-CH), 2.13 (d,
J = 13.5, 1H, CH SO Na), 2.35–2.42 (ddd, J = 19.0, 4.5, 3.0, 1H, 3-
CH exo), 2.57 (d, J = 13.5, 1H, CH SO O): 18.3
Na). 13C NMR (D
7-CH ), 18.7 (7-CH ), 25.6 (C-5), 25.9 (C-6), 42.0 (C-4), 42.3 (C-
), 47.6 (C-7), 58.5 (C-1), 59.5 (CH SO Na), 223.8 (C-2).
2
O, 22 °C); lit.:
À58.2 (c 0.885, H
2
O,
2
9
m
(0.83 g, 84%); mp 75 °C (ether/hexane); lit.:
76–77 °C.
À1
1
28
.
H NMR (D
2
O): 0.80
[a]
D
= +24.8 (c 1.12, CHCl
3
, 23 °C); lit.: +25.7 (c 1, CHCl , 23 °C).
3
s, 3H, 7-CH
3
3
IR
m
max (N) 2923, 2854, 1747 (C@O), 1457, 1375, 1328, 1275,
À1
2
1234, 1165, 1066, 1044, 963, 906, 851, 774, 706, 669, 634 cm
.
1
H NMR (CDCl
1.46 (m, 1H, 5-CH
J = 18.5, 1H, 3-CH
2.12 (t, J = 4.0, 1H, 4-CH), 2.43 (dt, J = 18.5, 4.0, 1H, 3-CH
3.42 (d, J = 11.5, 1H, CH Br), 3.64 (d, J = 11.5, 1H, CH
Br). 13C NMR
CDCl ): 19.8 (7-CH ), 20.0 (7-CH ), 26.2 (C-5), 27.2 (C-6), 28.9
(CH Br), 42.5 (C-3), 43.4 (C-4), 47.8 (C-7), 59.8 (C-1), 215.1 (C-2).
3
): 0.96 (s, 3H, 7-CH
endo), 1.54–1.61 (m, 1H, 6-CH
endo), 2.00–2.08 (m, 1H), 2.11–2.15 (m, 1H),
exo),
3
), 1.12 (s, 3H, 7-CH
3
), 1.40–
2
2
2
2
endo), 1.93 (d,
2
2
2
2
2
(
3
3
3
2
2
2
2
2
(
3
3
3
4
2
.4. (1S,4R)-1-(Iodomethyl)-7,7-dimethylbicyclo-[2.2.1]heptan-
-one 5
2
+
HRMS (EI, MeOH) m/z calcd for C10H15OBr [M+Na] : 253.0203;
found: 253.0200.
A solution of iodine (0.5 g, 1.97 mmol) in DCM (100 mL) was
vigorously mixed with a solution of sodium sulfinate 6 (0.54 g,
.16 mmol) in water (50 mL) in a separating funnel. The yellow or-
4.6. (1S,4R)-1-(Chloromethyl)-7,7-dimethylbicyclo-
[2.2.1]heptan-2-one 3
2
ganic phase was placed in a round-bottomed flask and stirred at
room temperature for 1.5 h. The solution was then washed with
water (50 mL) and the aqueous layer was extracted with ether
4.6.1. Method A: from sulfonyl chloride 9
Copper(II) chloride (0.02 g, 1.24 mol %) and triethylammonium
chloride (0.03 g, 1.82 mol %) were added to a solution of (+)-cam-
phor-10-sulfonyl chloride 9 (3.0 g, 11.96 mmol) in dry toluene
(15 mL). The resulting mixture was heated under nitrogen at
110 °C for 4 h. The solvent was removed under reduced pressure
and the residue was taken up in DCM (30 mL). The catalyst system
was then precipitated using methanol (5 mL) and the organic layer
was filtered and washed with 10% sodium hydrogen carbonate
solution (20 mL) and with water (20 mL). The extract was dried
and evaporated under reduced pressure to afford (+)-10-chloro-
camphor 3 as a white solid (2.19 g, 89%) which was recrystallised
from methanol.
(
50 mL). The combined organic extracts were washed with satu-
rated aqueous sodium sulfite (50 mL), dried and evaporated to af-
ford (À)-10-iodocamphor 5 as a white solid (0.36 g, 65%); mp 69 °C
2
8
28
(
(
1
(
1
1
2
1
CH
DCM); lit.: 71 °C. [
a
m
]
D
= À20.1 (c 1.28, CHCl
3
, 23 °C); lit.: À20.4
c 1, CHCl
3
, 23 °C). IR
max (N) 2921, 1743 (C@O), 1456, 1417, 1375,
À1
1
297, 1213, 1188, 1163, 1063, 1038, 955, 891, 766 cm . H NMR
CDCl ): 0.91 (s, 3H, 7-CH ), 1.08 (s, 3H, 7-CH ), 1.40 (t, J = 9.5,
H, 5-CH endo), 1.62 (t, J = 9.5, 1H, 6-CH endo), 1.92 (d, J = 18.5,
H, 3-CH endo), 1.96–2.05 (m, 2H, 5-CH exo and 6-CH exo),
.17 (app dd, J = 5.5, 2.5, 1H, 4-CH), 2.41 (ddd, J = 18.5, 5.0, 2.0,
H, 3-CH exo), 3.13 (d, J = 11.0, 1H, CH I), 3.32 (d, J = 11.0, 1H,
I). C NMR (CDCl ): 0.3 (CH I), 19.6 (7-CH ), 19.8 (7-CH ),
3
3
3
2
2
2
2
2
2
2
1
3
2
3
2
3
3
2
1
6.2 (C-5), 30.0 (C-6), 42.5 (C-3), 43.5 (C-4), 47.8 (C-7), 58.6 (C-
), 214.7 (C-2). HRMS (EI, MeOH): m/z calcd for
4.6.2. Method B: from sulfonic acid 12
C
10
H15OI
(+)-Camphor-10-sulfonic acid 12 (1.00 g, 4.30 mmol) and tri-
phenylphosphine (6.77 g, 25.82 mmol) were dissolved in dry tolu-
ene (30 mL) under an atmosphere of nitrogen. Carbon tetrachloride
(1.66 mL, 17.21 mmol) was added dropwise via syringe, followed
by tributylamine (1.02 mL, 4.30 mmol) and the solution was
heated at reflux for 24 h. The solution was then allowed to cool
to room temperature and water (50 mL) was added. The phases
were mixed and separated and the aqueous phase was extracted
with DCM (2 Â 50 mL). The combined organic extracts were
washed with water (50 mL), dried and evaporated to afford a
brown solid (8.70 g) which was triturated with ether (ca. 20 mL)
and filtered. The filtrate was evaporated to yield a brown solid
which was purified by column chromatography on silica gel, elut-
+
[
M+Na] : 301.0064; found: 301.0077.
4
.5. (1S,4R)-1-(Bromomethyl)-7,7-dimethylbicyclo-
[
2.2.1]heptan-2-one 4
4
.5.1. Method A: from sodium sulfinate 6
A solution of bromine (0.1 mL, 1.97 mmol) in DCM (100 mL)
was vigorously mixed with a solution of sodium sulfinate 6
0.54 g, 2.16 mmol) in water (50 mL) in a separating funnel. The or-
(
ganic phase was removed and evaporated and the resulting solid
was dissolved in xylene (15 mL). The solution was heated at reflux
for 6 h. The solution was allowed to cool to room temperature,

F. W. Lewis et al. / Tetrahedron: Asymmetry 20 (2009) 1531–1535
1535
ing with ether/hexane (1:10) to afford two products. The first prod-
3617–3626; (l) Carmen Bernabeu, M.; Chinchilla, R.; Nájera, C. Tetrahedron Lett.
995, 36, 3901–3904; (m) Nájera, C.; Sansano, J. M.; Yus, M. J. Chem. Educ. 1995,
2, 664–665; (n) Chinchilla, R.; Galindo, N.; Nájera, C. Tetrahedron 1996, 52,
035–1046; (o) Caturla, F.; Nájera, C. Tetrahedron Lett. 1996, 37, 2833–2836; (p)
Mori, Y.; Yaegashi, K.; Iwase, K.; Yamamori, Y.; Furukawa, H. Tetrahedron Lett.
1
7
1
uct to elute was (+)-10-chlorocamphor 3 as a white solid (0.65 g,
2
1
8
(
D
1%); mp 129 °C (ether/hexane); lit.: 131–132 °C. [a] = +39.7
21
c 1.16, EtOH, 16 °C); lit.: +41.8 (c 0.96, EtOH, 20 °C). IR mmax (N)
1996, 37, 2605–2608; (q) Caturla, F.; Nájera, C. Tetrahedron Lett. 1996, 37,
2
1
0
925, 1744 (C@O), 1455, 1414, 1375, 1301, 1219, 1168, 1101,
4787–4790; (r) Caturla, F.; Nájera, C. Tetrahedron 1997, 53, 11449–11464; (s)
À1
1
053, 1006, 982, 934, 853, 762, 716, 639 cm
.99 (s, 3H, 7-CH ), 1.13 (s, 3H, 7-CH ), 1.39–1.46 (m, 1H, 5-CH
endo), 1.92 (d, J = 18.5, 1H, 3-CH
3
. H NMR (CDCl ):
Caturla, F.; Nájera, C. Tetrahedron Lett. 1997, 38, 3789–3792; (t) Grigg, R.;
Nájera, C.; Sansano, J. M.; Yus, M. Synth. Commun. 1997, 27, 1111–1114; (u)
Caturla, F.; Nájera, C. Tetrahedron 1998, 54, 11255–11270; (v) Caturla, F.;
Nájera, C.; Varea, M. Tetrahedron Lett. 1999, 40, 5957–5960; (w) Mori, Y.;
Yaegashi, K.; Furukawa, H. Tetrahedron Lett. 1999, 40, 7239–7242; (x) Wolff, R.
R.; Basava, V.; Giuliano, R. M.; Boyko, W. J.; Schauble, J. H. Can. J. Chem. 2006, 84,
667–675.
3
3
2
endo), 1.48–1.54 (m, 1H, 6-CH
2
2
endo), 2.01–2.07 (m, 1H), 2.10 (t, J = 4.5, 1H, 4-CH), 2.18 (td,
J = 12.0, 4.0, 1H), 2.43 (dt, J = 18.5, 4.5, 1H, 3-CH exo), 3.62 (d,
J = 12.0, 1H, CH Cl), 3.81 (d, J = 12.0, 1H, CH ):
Cl). 13C NMR (CDCl
), 20.0 (7-CH ), 25.6 (C-5), 26.2 (C-6), 40.9 (CH Cl),
2.6 (C-3), 43.3 (C-4), 47.3 (C-7), 60.6 (C-1), 215.5 (C-2). HRMS
2
2
2
3
6
7
.
.
Egron, G. M.Sc. Thesis, Dublin University, 1998.
Asscher, M.; Vofsi, D. J. Chem. Soc. 1964, 4962–4971.
1
9.9 (7-CH
3
3
2
4
8. For examples of analogous thermally-induced loss of SO2 from camphor-8-
sulfonyl halides and camphor-9-sulfonyl halides, see: (a) Kipping, F. S.; Pope,
W. J. J. Chem. Soc. 1895, 371–398; (b) Tremaine Finch, A. M., Jr.; Vaughan, W. R.
J. Am. Chem. Soc. 1969, 91, 1416–1424.
9. (a) van Aller, R. T.; Scott, R. B., Jr.; Brockelbank, E. L. J. Org. Chem. 1966, 31,
2357–2365; (b) Truce, W. E.; Wolf, G. C. J. Org. Chem. 1971, 36, 1727–1732; (c)
Truce, W. E.; Heuring, D. L. J. Org. Chem. 1974, 39, 245–246; (d) Huang, W.-Y.;
Hu, L.-Q. J. Fluorine Chem. 1989, 44, 25–44; (e) King, M. D.; Sue, R. E.; White, R.
H.; Young, D. J. Tetrahedron Lett. 1997, 38, 4493–4496.
+
(
EI, MeOH) m/z calcd for C10
H
15OCl [M+H] : 187.0890; found:
1
87.0892. The second product to elute was bis(10-camphoryl)
disulfide 13 as a white solid (0.02 g, 3%); mp 233–234 °C (ether/
2
4
hexane); lit.: 236–238 °C. [
a
]
D
= À102.1 (c 0.94, CHCl
, 25 °C). IR max (N) 2927, 1738 (C@O),
453, 1412, 1375, 1301, 1219, 1168, 1102, 1062, 1006, 982, 944,
3
, 22 °C);
2
4
lit.: À103.66 (c 1, CHCl
3
m
1
8
CH
2
1
4
À1
1
59, 765, 711, 645 cm
), 1.07 (s, 6H, 2 Â 7-CH
H), 1.57–1.64 (m, 2H), 1.88 (d, J = 18.0, 2H, 2 Â 3-CH
.99–2.07 (m, 2H), 2.09 (t, J = 4.5, 2H, 2 Â 4-CH), 2.41 (dt, J = 18.0,
.5, 2H, 2 Â 3-CH exo), 2.82 (d, J = 13.0, 2H, 2 Â CH S), 3.27 (d,
): 19.5 (2 Â 7-CH ), 19.7
), 26.0 (2 Â C-5), 26.3 (2 Â C-6), 38.1 (2 Â CH S), 42.5
2 Â C-3), 42.9 (2 Â C-4), 47.3 (2 Â C-7), 60.7 (2 Â C-1), 216.5
.
H NMR (CDCl
), 1.37–1.46 (m, 2H), 1.47–1.53 (m,
endo),
3
): 0.92 (s, 6H, 2 Â 7-
10. (a) Sell, T.; Laschat, S.; Dix, I.; Jones, P. G. Eur. J. Org. Chem. 2000, 4119–4124; (b)
Monsees, A.; Dingerdissen, U.; Laschat, S.; Sell, T. Eur. Pat. Appl. EP 1 201 673
A1, 2002.; (c) Chelucci, G.; Baldino, S. Tetrahedron: Asymmetry 2006, 17, 1529–
3
3
2
1
536.
11. Bica, K.; Gmeiner, G.; Reichel, C.; Lendl, I.; Gaertner, P. Synthesis 2007, 1333–
338.
1
2
2
1
1
2. Zhang, J.; Saito, S.; Koizumi, T. J. Org. Chem. 1998, 63, 5423–5429.
13
J = 13.0, 2H, 2 Â CH
2
S). C NMR (CDCl
3
3
3. Verdaguer, X.; Vázquez, J.; Fuster, G.; Bernardes-Génisson, V.; Greene, A. E.;
Moyano, A.; Pericàs, M. A.; Riera, A. J. Org. Chem. 1998, 63, 7037–7052.
4. (a) Takahashi, T.; Nakao, N.; Koizumi, T. Chem. Lett. 1996, 207–208; (b)
Takahashi, T.; Nakao, N.; Koizumi, T. Tetrahedron: Asymmetry 1997, 8, 3293–
(2 Â 7-CH
(
(
3
2
1
+
2 Â C-2). HRMS (EI, MeOH) m/z calcd for C20
30 2 2
H O S [M+Na] :
3308.
3
89.1584; found: 389.1531.
15. (a) Money, T. Nat. Prod. Rep. 1985, 2, 253–289; (b) Kagawa, M. Pharm. Bull.
1
1
5
956, 4, 423–427; (c) Hutchinson, J. H.; Money, T.; Piper, S. E. Can. J. Chem.
986, 64, 854–860; (d) Liu, H.-J.; Llinas-Brunet, M. Can. J. Chem. 1988, 66, 528–
30.
Acknowledgements
1
6. (a) Liu, H.-J.; Ralitsch, M. J. Chem. Soc., Chem. Commun. 1990, 997–999; (b)
Tachibana, S.; Ohno, Y.; Fujihara, Y.; Okada, Y.; Sugiura, M.; Takagi, S.; Nomura,
M. J. Oleo Sci. 2006, 55, 181–189; (c) Srikrishna, A.; Beeraiah, B.; Satyanarayana,
G. Tetrahedron: Asymmetry 2006, 17, 1544–1548; (d) Srikrishna, A.; Gowri, V.
Tetrahedron: Asymmetry 2007, 18, 1663–1666.
The authors gratefully acknowledge Dr. John E. O’Brien and Dr.
Manuel Reuther for obtaining NMR spectra and Dr. Martin Feeney
for obtaining mass spectra. One of us (F.W.L.) received financial
support from Trinity College Dublin.
17. Forster, M. O. J. Chem. Soc. 1902, 264–274.
8. (a) Henderson, G. G.; Heilbron, I. M.; Howie, M. J. Chem. Soc. 1914, 1367–1372;
b) Henderson, G. G.; Mair, J. A. J. Chem. Soc. 1923, 1155–1161; (c) Buchbauer,
G.; Freudenreich, S.; Hampl, C.; Haslinger, E.; Robien, W. Monatsh. Chem. 1984,
15, 509–517.
1
(
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