A cationic driven tandem ring-enlargement-annulation reaction for the rapid assembly of the cis-fused bicyclo[3.2.0]heptane framework

Article abstract of DOI:10.1016/S0040-4020(00)00391-4

The first intramolecular interception of a thionium cation generated through a cyclopropylcarbinyl-cyclobutyl ring expansion with an in situ formed enol is reported. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00391-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4747±4752
A Cationic Driven Tandem Ring-Enlargement-Annulation
Reaction for the Rapid Assembly of the cis-Fused
Bicyclo[3.2.0]heptane Framework
*
Bernhard Witulski, Uwe Bergstraûer and Matthias Goûmann
È
È
È È
Fachbereich Chemie, Universitat Kaiserslautern, Erwin Schrodinger Straûe, D-67663 Kaiserslautern, Germany
Received 15 April 2000; accepted 9 May 2000
AbstractÐThe ®rst intramolecular interception of a thionium cation generated through a cyclopropylcarbinyl-cyclobutyl ring expansion
with an in situ formed enol is reported. q 2000 Published by Elsevier Science Ltd.
Introduction
with n-butyllithium and adds to carbonyl compounds to give
the b-hydroxy sul®de 2, that thereupon may rearrange under
acid catalysis in wet benzene to cyclobutanone 4 or under
anhydrous reaction conditions to cyclobutenyl phenyl
sul®de 5 (Scheme 1).
The interplay between the release of ring strain and the
directional power of 1-donor-substituents in cyclopropyl
carbinyl cations generated from oxaspiropentanes or
1-donor-substituted cyclopropylcarbinols has made cyclo-
propylcarbinyl-cyclobutyl ring enlargement reactions to a
powerful method for the construction of four-membered
rings.1 Readily available 1-donor-substituted cyclopropyl-
carbinols rearrange with ease under acid catalysis and are
important precursors for the synthesis of cyclobutanones.
They have found wide use in the synthesis of natural
products2 and recent progress of asymmetric versions3
guarantee future applications.
The driving force for the ring expansion of 2 to 4 and 5,
respectively, is attributed to the directional power of the
sulfur atom and its aptitude to stabilise the adjacent
cationic centre in the a-thiocarbocation (thionium ion)
intermediate 3. However, although a-thiocarbocationsÐ
more generally associated with, and obtained in the
Pummerer reaction6Ðare considered as versatile reactive
intermediates for carbon-carbon bond forming processes,
the reaction of the a-thiocarbocation 3 with nucleo-
philes other than water has not been described yet.7
We report here the ®rst intramolecular interception of
a thionium ion generated via a ring enlargement process
related to the formation of 3 with a nucleophilic carbon
species.
Particularly the ambivalent aptitude of sulfur4 to stabilise
adjacent anionic as well as cationic centres has proved to be
bene®cial for the development of cyclopropyl phenyl
sul®des as reagents for the four membered ring synthesis.1,5
Cyclopropyl phenyl sul®de (1) is selectively deprotonated
Scheme 1.
Keywords: annulation; carbonium ions; cyclobutanes; cyclisations; sulfones; tandem reactions.
* Corresponding author. Tel.: 149-631-205-2032; fax: 149-631-205-3921; e-mail: witulski@rhrk.uni-kl.de
0040±4020/00/$ - see front matter q 2000 Published by Elsevier Science Ltd.
PII: S0040-4020(00)00391-4

4748
B. Witulski et al. / Tetrahedron 56 (2000) 4747±4752
Scheme 2. Reagents and conditions: (i) n-BuLi (2 equiv.), THF, 278 to 2208C, then Me3SiCl (2.5 equiv.), 278 to 208C, then HOAc/H2O, (96%); (ii) (COCl)2,
DMSO, CH2Cl2, 2788C, (65%); (iii) 1 (1.2 equiv.), n-BuLi, THF, 08C, then addition to the aldehyde, 2788C, THF, (45%); (iv) TsOH´H2O (1 equiv.), wet
benzene, 70±808C, 8 (10±26%), 9 (20±32%); (v) mCPBA (1 equiv.), CH2Cl2, 2158C, (76%); (vi) mCPBA (2 equiv.), 2158C, (96%).
Results and Discussion
also allowed the isolation of 8 effectively. Furthermore
treatment of the received reaction mixture with an excess
of m-CPBA permitted the isolation of the sulfone 11 in high
yields after crystallisation from CHCl3/pentane (colourless
plates, mp 958C).
At the outset of our studies we intended the synthesis of the
cyclobutanone 8 through the acid catalysed ring expansion
of alcohol 7, which was smoothly obtained from 5-hexyn-1-
ol (6) as outlined in Scheme 2. Surprisingly, acidi®cation of
7 with p-toluenesulfonic acid in re¯uxing wet benzene gave
besides the anticipated cyclobutanone 8 also the unexpected
bicyclo[3.2.0]heptane 9 as a single diastereomer. The ring
enlargement products were received as a mixture dif®cult to
separate by simple chromatographic means in variable
yields ranging from 10 to 26% for 8 and from 20 to 32%
for 9, respectively.8
The structural assignment of 11 having a cis-fused bicy-
clo[3.2.0]heptane framework with an endo-oriented acetyl
group at C-2 was unambiguously revealed by the X-ray
crystal structure analysis (Fig. 1)9 and 2D NMR spectro-
scopy (Table 1).
The S atom is tetrahedrally bonded to two C and O atoms
with tetrahedral angles ranging from 107.18(8) to
108.01(8)8 with exception of the O±S±O angle which is
118.14(9)8. The ®ve-membered ring shows an envelop
conformation (dihedral angle between least squares plane
However, the sulfoxides 10 (mixture of diastereomers) were
obtained analytically pure after oxidation of 9 with m-CPBA
followed by chromatography on silica gel. A procedure that
Ê
Figure 1. Molecular structure of 11. Selected bond lengths [A] and angles [8]: C1±C2 1.534(2), C1±C5 1.575(2), C1±C7 1.551(2), C2±C3 1.550(3), C3±C4
1.528(3), C4±C5 1.522(3), C5±C6 1.530(3), C6±C7 1.528(3); C2±C1±C5 106.13(12), C2±C1±C7 119.29(14), C7±C1±C5 89.22(14), C1±C2±C3
103.01(14), C2±C3±C4 103.3(2), C3±C4±C5 104.7(2), C4±C5±C1 105.70(14), C1±C5±C6 89.05(14), C5±C6±C7 91.7(2), C6±C7±C1 90.02(14).

B. Witulski et al. / Tetrahedron 56 (2000) 4747±4752
4749
Table 1. NMR data of compound 11 (spectra recorded in CDCl3. Assign-
ment based on H,H-COSY, C,H-COSY and DEPT spectra)
Under these conditions a rearrangement of the cyclopropyl-
carbinol moiety was not observed.
Position number
d1H (mult.)
J (Hz)
d13
C
DEPT
Gratifyingly, when ketone 13 was subjected to the reaction
condition operable for the rearrangement of 7 to 8 and 9
(TsOH´H2O, wet benzene, 70±808C) the annulative ring
enlargement product 9 was now obtained in 89% yield.11
Importantly, this conversion was accomplished with
complete diastereoselectivity, establishing three contiguous
stereocenters in a single step. The fact that 9 was received as
a single product and no cyclobutanone formation was
observed indicated that the intramolecular reaction of the
enol unit in 14b with the a-thiocarbocationÐgenerated
through the ring expansion process starting with the proto-
nation of 13Ðmust have been orders of magnitude faster
than the competitive hydrolysis of the a-thiocarbocation in
14a/14b.
1
2
3
4
5
6
7
8
±
3.38 (dd)
2.15 (m), 2.3 (m)
1.63 (m)a
3.35 (m)
1.50 (m), 2.05 (m)
2.30 (m), 2.50 (m)
±
±
11.5, 6.8
73.2
53.7
30.5
30.9
43.1
20.7
20.9
207.1
31.2
136.9
129.3
129.1
133.8
s
d
t
t
d
t
±
±
±
±
±
±
±
±
t
s
q
s
d
d
d
9
2.11 (s)
±
7.92 (dd)
7.57 (dd)
7.67 (tt)
10
11
12
13
8.2, 1.7
8.2, 7.4
7.4, 1.7
a Overlapping signals.
In conclusion we have found a novel diastereoselective
tandem ring-enlargement±annulation reaction sequence
that is mediated by the strong directional power of the
phenylthio group and its aptitude to stabilise an adjacent
cationic centre suf®ciently for further annulative carbon±
carbon bond forming processes. If this novel tandem
reaction is suitable for the rapid assembly of more function-
alised cis-fused bicyclo[3.2.0]-frameworks as found in
natural products like kelsoene12 and poduran,13 has to be
determined in future applications.
C2/C3/C4 and C1/C2/C4/C5 of 40.38). The four-membered
ring is planar and making a dihedral angle of 60.68 with the
best least squares plane through C1/C2/C4/C5 of the ®ve
membered ring. All bond parameters are in good agreement
with the structure of 2,5-dimethyl-1-(phenylsulfonyl)bi-
cyclo[3.2.0]heptane-2,3-diol, published by Zuckerman-
Schpector and Monteiro.10
The formation of the product 9 may be best explained by a
tandem reaction11 sequence implying as ®nal step the intra-
molecular addition of an in situ formed enol as carbon
nucleophile to the a-thiocarbocation generated during the
anticipated cyclopropylcarbinyl-cyclobutyl ring expansion.
Indeed the formation of an enol and likewise a ketone
moiety via the hydration of the acetylene unit of 7 followed
by a desilylation step seems to be likely under the reaction
conditions employed.
Experimental
General procedures
Reactions requiring anhydrous conditions were performed
using ¯ame-dried glassware and conducted under an
atmosphere of nitrogen. Anhydrous solvents were prepared
in accordance with standard protocols. Compounds were
puri®ed by chromatography on silica gel 60 (63±
230 mesh). Melting points were measured on a BuÈchi
melting-point apparatus and are uncorrected. IR spectra
were recorded on a Perkin±Elmer FT-IR spectrometer
16PC. Spectra were recorded as thin ®lms or in KBr pellets.
Further support for the suggested tandem reaction sequence
was gained from the acid catalysed ring-enlargement-annu-
lation reaction of ketone 13 (Scheme 3). The latter was
obtained from 7 by desilylation to 12 followed by the care-
ful hydration of the acetylene unit with mercury(II) acetate
and p-toluenesulfonic acid monohydrate in THF at 808C.
Scheme 3. Reagents and conditions: (i) K2CO3, MeOH, 208C (77%); (ii) TosOH´H2O (1 equiv.), Hg(OAc)2 (0.3 equiv.), THF, 808C (62%); (iii) TsOH´H2O
(1 equiv.), benzene, 70±808C (89%).

4750
B. Witulski et al. / Tetrahedron 56 (2000) 4747±4752
NMR spectra were recorded in CDCl3 as solvent on Bruker
AMX 400 and Bruker AC 200 spectrometers with either
TMS or solvent as internal reference; J-values are given
in Hz with an accuracy of ^0.2. Assignments were
supported by DEPT spectra and in the case of 11 by 2D
NMR experiments. Elemental analyses were carried out
on a Perkin±Elmer EA 240 elemental analyser and on a
Perkin±Elmer 2400 CHN elemental analyser. Mass spectra
were recorded under EI conditions on a Finnigan MAT 90
spectrometer.
ether were added. The organic layer was separated and the
aqueous layer was extracted with diethyl ether. The
combined organic layers were dried with MgSO4 and the
crude product was puri®ed by column chromatography on
silica gel (diethyl ether/hexanesˆ2:8 (v/v)) to afford 7
(5.81 g, 45%) as a colourless oil. IR (®lm): n 3432, 3060,
1
2957, 2174, 1584, 1480, 1439, 760, 739 cm21; H NMR
(400 MHz): dˆ7.46 (2H, d), 7.26 (2H, t), 7.17 (1H, t),
3.25±3.35 (1H, m), 2.21 (2H, t, Jˆ6.9 Hz), 1.95 (1H, s,
OH), 1.75±1.85 (1H, m), 1.50±1.75 (3H, m), 0.95±1.10
(4H, m), 0.14 (9H, s); 13C NMR (100 MHz): dˆ136.3 (s),
129.0 (d), 128.6 (d), 125.9 (d), 107.0 (s), 84.8 (s), 75.6 (d),
33.8 (t), 31.3 (s), 24.9 (t), 19.5 (t), 14.0 (t), 13.9 (t), 0.07 (q);
MS, m/z (%): 318 (M1, 14), 285 (2), 272 (4), 149 (25), 91
(23), 75 (37), 73 (100), 45 (5).
6-(Trimethylsilyl)-5-hexyn-1-ol. 5-Hexyn-1-ol (6) (20 g,
0.2 mol) was added to a solution of n-BuLi (294 mL,
1.5 M solution in hexane) in THF (400 mL) at 2788C.
The solution was allowed to warm to 2208C and was stirred
for 30 min. After addition of Me3SiCl (54 g, 0.5 mol) at
2788C the mixture was allowed to warm to room tempera-
ture during 4 h. Then 5% acetic acid (480 mL) was added
and the mixture was stirred vigorously for 1 h at room
temperature, concentrated and extracted with diethyl ether.
The combined organic extracts were washed with brine and
dried with MgSO4. The diethyl ether solution was concen-
trated in vacuo and was puri®ed via vacuum distillation to
afford 6-(trimethylsilyl)-5-hexyn-1-ol (32.6 g, 96%) as a
colourless oil, bp: 80±908C/0.1 mmHg; IR (®lm): n 3345,
2957, 2900, 2868, 2174, 1457, 1452, 1436, 1430,
2-[50-(Trimethylsilyl)pent-40-ynyl]cyclobutanone (8) and
bicyclo[3.2.0]trans-1-phenylthio-2-aceto-heptane (9). A
stirred solution of 7 (2.70 g, 8.48 mmol) and p-toluenesul-
fonic acid monohydrate (1.61 g, 8.46 mmol) in benzene
(40 mL) was heated for 2 h under re¯ux. After cooling to
room temperature, saturated sodium bicarbonate solution
(40 mL) was added and the organic layer was separated.
The aqueous layer was extracted with diethyl ether and
the combined organic layers were washed with brine and
dried with MgSO4. The crude product was puri®ed by
column chromatography on silica gel (diethyl ether/
hexanesˆ1:19 (v/v)) to afford a mixture (869 mg) of 9
(2.71 mmol, 32%) and 8 (0.93 mmol, 11%).
1046 cm21
;
1H NMR (400 MHz): dˆ3.65 (2H, t, Jˆ
6.1 Hz), 2.26 (2H, t, Jˆ6.9 Hz), 2.21 (1H, s, OH), 1.59±
1.67 (4H, m), 0.14 (9H, s,); 13C NMR (100 MHz): dˆ107.1
(s), 84.7 (s), 62.1 (t), 31.6 (t), 24.8 (t), 19.5 (t), 0.04 (q); MS,
m/z (%): 170 (M1,1), 169 (2), 168 (2), 167 (12), 153 (3), 125
(5), 111 (9), 96 (12), 75 (100), 73 (40), 59 (11).
2-[50-(Trimethylsilyl)pent-40-ynyl]cyclobutanone (8) and
bicyclo[3.2.0]trans-1-phenylsul®nyl-2-aceto-heptane (10).
To the mixture of 8 and 9 in CH2Cl2 (40 mL) was added
mCPBA (576 mg, 3.34 mmol) at 2158C over a period of
3 h. The resulting reaction mixture was washed with satu-
rated sodium bicarbonate solution (30 mL) and brine
(30 mL), dried with MgSO4 and evaporated. The obtained
residue was chromatographed on silica gel (diethyl ether/
hexanesˆgradient from 1:19 to 1:1 (v/v)) to afford 8
(172 mm, 86%) as a colourless liquid (bp: 95±1058C/
0.1 mmHg) and 10 (541 mg, 76%) as a mixture of dia-
stereomers. 8: IR (®lm): n 2957, 2863, 2173, 1779,
6-(Trimethylsilyl)-5-hexyn-1-al. DMSO (8.4 mL, 119.4
mmol) was added to a solution of oxalyl chloride (5.2 mL,
59.5 mmol) in CH2Cl2 (200 mL) at 2788C. After 3 min
6-(trimethylsilyl)-5-hexyn-1-ol (8.46 g, 49.5 mmol) was
added followed after 15 min by NEt3 (34.5 mL,
247.4 mmol). The mixture was stirred for 15 min at
2788C and allowed to warm to room temperature. CH2Cl2
(200 mL) was added and the reaction mixture was washed
with 1 M HCl (100 mL), saturated sodium bicarbonate solu-
tion, brine and dried with MgSO4. The resulting solution
was concentrated in vacuo and was puri®ed via vacuum
distillation to afford 6-(trimethylsilyl)-5-hexyn-1-al (5.44 g,
65%) as a colourless oil, bp: 65±708C/0.1 mmHg; IR (®lm):
n 2957, 2174, 1738, 1455, 1435 cm21; 1H NMR (400 MHz):
dˆ9.81 (1H, s), 2.59 (2H, td, Jˆ7.1 Hz, Jˆ1.0 Hz), 2.30
(2H, t, Jˆ7.1 Hz), 1.85 (2H, quint, Jˆ7.1 Hz), 0.15 (9H, s);
13C NMR (100 MHz): dˆ201.8 (d), 105.8 (s), 85.7 (s), 42.5
(t), 21.1 (t), 19.1 (t), 20.05 (q); MS, m/z (%): 169 (M1, 3),
153 (46), 140 (5), 125 (9), 97 (75), 75 (100), 73 (52).
1
1457 cm21; H NMR (400 MHz): dˆ3.25±3.4 (1H, m),
2.8±3.1 (2H, m), 2.1±2.4 (3H, m), 1.5±1.9 (5H, m), 0.14
(9H, s); 13C NMR (100 MHz): dˆ211.7 (s), 106.6 (s), 84.8
(s), 59.9 (d), 44.4 (t), 28.6 (t), 26.0 (t), 19.6 (t), 16.8 (t), 0.0
(q); MS, m/z (%): 209 (M1, 27), 193 (64), 180 (40), 165
(25), 137 (20), 123 (16), 109 (33), 97 (22), 83 (23), 75 (87),
73 (100), 59 (34); Anal. Calcd. for C112H20OSi: C, 69.17; H,
9.67. Found: C, 68.82; H, 9.71. 10: H NMR (400 MHz):
dˆ7.48±7.76 (10H, m), 3.34 (1H, dd, Jˆ11.7 Hz,
Jˆ6.6 Hz), 3.27±3.34 (1H, m), 3.02 (1H, dd, Jˆ11.7 Hz,
Jˆ6.6 Hz), 2.95±3.03 (1H, m), 2.56±2.63 (1H, m), 2.04±
2.42 (6H, m), 2.20 (3H, s), 1.90 (3H, s), 1.50±1.60 (4H, m),
1.25±1.41 (2H, m); 13C NMR (100 MHz): dˆ207.3, 140.6,
131.3, 131.1, 128.6, 125.5, 124.8, 70.4, 69.9, 53.9, 51.7,
40.8, 39.7, 31.0, 30.6, 30.54, 30.49, 29.7, 29.0, 21.1,
20.91, 20.88, 20.78; Anal. Calcd. for C15H18O2S: C,
68.67; H, 6.92. Found: C, 68.39; H, 6.90.
6-(Trimethylsilyl)-1-(10-phenylthiocyclopropyl)hex-5-yn-
1-ol (7). n-BuLi (33 mL, 1.5 M solution in hexane) was
added to a stirred solution of cyclopropyl phenyl sul®de
(1) (7 mL, 0.05 mol) in THF (40 mL) at 08C. The resulting
solution was stirred for 90 min at 08C and transferred by
syringe into a solution of 6-(trimethylsilyl)-5-hexyn-1-al
(6.72 g, 0.04 mmol) in THF (40 mL) at 2788C. After the
addition was completed the mixture was warmed to room
temperature during 30 min, and was kept at room tempera-
ture for additional 30 min. Afterwards, brine and diethyl
2-[50-(Trimethylsilyl)pent-40-ynyl]cyclobutanone (8) and
bicyclo[3.2.0]trans-1-phenylsulfonyl-2-aceto-heptane (11).
To a solution of 547 mg of a mixture of 8 (1.64 mmol) and

B. Witulski et al. / Tetrahedron 56 (2000) 4747±4752
4751
9 (0.82 mmol) in CH2Cl2 (20 mL) was added mCPBA
(512 mg, 2.98 mmol) at 2158C. The crude product crystal-
lised overnight and was washed several times with diethyl
ether/hexanesˆ1:19 (v/v). Chromatography on silica gel
with diethyl ether/hexanes (gradient from 1:19 to 1:1
(v/v)) afforded 8 (150 mg, 44%) and 11 (220 mg, 96%).
Spectroscopic data of 11: colourless crystals, mp 958C
(from CHCl3±pentane); IR (®lm): n 3003, 2951, 2860,
combined organic layers were washed with brine and
dried with MgSO4 to afford 9 (40 mg, 89%). An analytical
pure sample was obtained after column chromatography on
silica using diethyl ether/hexanesˆ1:9 (v/v) as eluent. IR
(®lm): n 3058, 2955, 2857, 1704, 1583, 1474, 1438, 1360,
1300, 1274, 1245, 1211, 1185, 1161, 1129, 1068, 1025, 948,
902, 749, 695 cm21; 1H NMR (200 MHz): dˆ7.52 (2H, d),
7.31±7.39 (3H, m), 2.98±3.04 (1H, m), 2.87 (1H, dd,
Jˆ11.7 Hz, Jˆ6.6 Hz), 1.96±2.45 (5H, m), 2.27 (3H, s),
1.75±1.89 (1H, m), 1.38±1.59 (2H, m); 13C NMR
(50 MHz): dˆ208.5 (s), 134.9 (d), 133.3 (s), 128.9 (d),
128.4 (d), 58.7 (d), 58.4 (s), 47.9 (d), 31.9 (q), 30.4 (t),
27.3 (t), 26.4 (t), 20.8 (t); MS, m/z (%): 246 (M1, 45), 218
(73), 203 (32), 137 (17), 110 (66), 109 (35), 93 (27), 91 (22),
77 (21), 65 (11), 43 (100); Anal. Calcd. for C15H18OS: C,
73.13; H, 7.36. Found: C 72.92; H, 7.17.
1713, 1443, 1365, 1144, 763, 721 cm21
;
1H NMR
(400 MHz): dˆ7.92 (2H, dd, Jˆ8.2 Hz, Jˆ1.7 Hz), 7.67
(1H, tt, Jˆ7.4 Hz, Jˆ1.7 Hz), 7.57 (2H, dd, Jˆ8.2 Hz,
Jˆ7.4 Hz), 3.38 (1H, dd, Jˆ11.5 Hz, Jˆ6.8 Hz), 3.35
(1H, m), 2.66 (1H, m), 2.50 (1H, m), 2.30 (1H, m), 2.15
(1H, m), 2.11 (3H, s), 2.05 (1H, m), 1.63 (2H, m), 1.50 (1H,
m); 13C NMR (100 MHz): dˆ207.1 (s), 136.9 (s), 133.8 (d),
129.3 (d), 129.1 (d), 73.2 (s), 53.7 (d), 43.1 (d), 31.2 (q),
30.9 (t), 30.5 (t), 20.9 (t), 20.7 (t); MS, m/z (%) 278 (M1, 2),
259 (1), 137 (34), 93 (46), 77 (21), 43 (100); Anal. Calcd.
for C15H18O3S: C, 64.72; H, 6.52. Found: C, 64.72; H, 6.46.
Acknowledgements
1-(10-Phenylthiocyclopropyl)hex-5-yn-1-ol (12). Potas-
sium carbonate (0.32 g, 2.32 mmol) was added to a stirred
solution of 7 (1.52 g, 4.77 mmol) in methanol (26 mL) at
208C. After 24 h another portion of potassium carbonate
(0.16 g, 1.16 mmol) was added. After 24 h the reaction
mixture was puri®ed by column chromatography on silica
gel (diethyl ether/hexanesˆ2:8 (v/v)) to afford 12 (0.91 g,
77%) as colourless oil. IR (®lm): n 3424, 3297, 3075, 3059,
3004, 2948, 2866, 2115, 1583, 1479, 1455, 1439, 1384,
1328, 1304, 1247, 1156, 1088, 1072, 1025, 968, 740, 692,
637 cm21; MS, m/z (%): 246 (M1, 39), 179 (13), 161 (24),
149 (81), 135 (29), 117 (91), 110 (52), 91 (71), 77 (34), 69
(34), 41 (100), 39 (46); Anal. Calcd. for C15H18OS: C,
73.13; H, 7.36. Found: C, 72.73; H, 7.27.
We would like to thank Prof. Dr M. Regitz for his generous
support of this work and we are indebted to the Fonds der
Chemischen Industrie for ®nancial support.
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6-Hydroxy-6-(1-phenylthiocyclopropyl)-hexan-2-one (13).
A stirred solution of 12 (162 mg, 0.656 mmol), p-toluene-
sulfonic acid monohydrate (130 mg, 0.68 mmol) and
mercury(II) acetate (60 mg, 0.19 mmol) in THF (20 mL)
was heated for 1 h under re¯ux. After cooling to room
temperature the mixture was partitioned between diethyl
ether (20 mL) und saturated sodium bicarbonate solution
(15 mL). The aqueous layer was extracted with diethyl
ether. The combined organic layers were washed with
brine, dried with MgSO4 and puri®ed by column chromato-
graphy on silica gel (diethyl ether/hexanesˆ3:7 (v/v)) to
afford 13 (108 mg, 62%) as colourless oil. 1H NMR
(200 MHz): dˆ7.45 (2H, d), 7.11±7.29 (3H, m), 3.32
(1H, d), 2.42 (2H, t, Jˆ6.5 Hz), 2.20 (1H, br s, OH), 2.10
(s, 3H), 1.43±1.79 (4H, m), 0.91±1.09 (4H, m); 13C NMR
(50 MHz): dˆ209.1 (s), 136.3 (s), 129.1 (d) 128.7 (d) 126.0
(d), 75.7 (d), 43.3 (t), 34.4 (t), 31.1 (s), 29.8 (q), 20.2 (t),
13.9 (t) 13.6 (t); MS, m/z (%): 264 (M1, 15), 246 (9), 188
(31), 178 (100), 150 (26), 115 (41), 97 (23), 77 (13), 71 (30),
43 (65).
5. (a) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Rigby, J. H.;
Bogdanowicz, M. J. J. Am. Chem. Soc. 1977, 99, 3080. (b) Trost,
B. M.; Keeley, D. E.; Arndt, H. C.; Bogdanowicz, M. J. J. Am.
Chem. Soc. 1977, 99, 3088.
6. (a) De Lucchi, O.; Miotti, U.; Modena, G. Org. React. 1991, 40,
157. (b) Grierson, D. S.; Husson, H.-P. Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 6,
p 909. (c) Kennedy, M.; McKervey, M. A. Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon: Oxford, 1991; Vol. 7,
p 193. (d) Padwa, A.; Kuethe, J. T. J. Org. Chem. 1998, 63, 4256.
7. For the intramolecular interception of cyclic sulfonium salts by
nitrogen, oxygen and sulfur nucleophiles see: (a) Eames, J.;
Kuhnert, N.; Sansbury, F. H.; Warren, S. Synlett 1999, 1211.
(b) Eames, J.; Kuhnert, N.; Warren, S. Synlett 1999, 1215.
(c) Eames, J.; Jones, R. V. H.; Warren, S. Tetrahedron Lett.
1996, 37, 707. (d) Coldham, I.; Warren, S. J. Chem. Soc., Perkin
Trans 1 1993, 1637.
Bicyclo[3.2.0]trans-1-phenylthio-2-aceto-heptane (9). A
stirred solution of 13 (48 mg, 0.181 mmol) and p-toluene-
sulfonic acid monohydrate (40 mg, 0.21 mmol) in benzene
(10 mL) was heated for 45 min under re¯ux. After cooling
to room temperature, saturated sodium bicarbonate solution
(10 mL) was added and the organic layer was separated. The
aqueous layer was extracted with diethyl ether and the
8. Yields were determined by NMR data from the mixture of 8 and
9.
9. Crystal data for 11: C15H18O3S, Mˆ278.35, Tˆ293(2) K, triclinic,
Ê
space group P1, aˆ8.374(2), bˆ8.469(2), cˆ10.889(2) A,

4752
B. Witulski et al. / Tetrahedron 56 (2000) 4747±4752
Ê 3
aˆ100.39(3)8, bˆ99.88(3)8, gˆ106.01(3)8, Vˆ709.8(2) A , Zˆ2,
Dcˆ1.302 g cm23, mˆ0.229 mm21, re¯ections collectedˆ5479,
independent re¯ectionsˆ2537 (Rintˆ0.0250), re¯ections with I $
11. (a) Tietze, L. F. Chem. Rev. 1996, 96, 115. (b) Ho, T. L.
Tandem Organic Reactions; Wiley: New York, 1992; for recent
examples of cationic tandem reactions in total syntheses see:
(c) Corey, E. J.; Luo, G.; Lin, L. S. Angew. Chem., Int. Ed. Engl.
1998, 37, 1126. (d) Romero, A. G.; Leiby, J. A.; Mizsak, S. A.
J. Org. Chem. 1996, 61, 6974. (e) Burke, S. D.; Kort, M. E.;
Strickland, S. M. S.; Organ, H. M.; Silks, L. A. Tetrahedron
Lett. 1994, 35, 1503. (f) Harring, S. R.; Livinghouse, T.
Tetrahedron 1994, 50, 9229.
2sꢀI† ˆ 2280; ®nal
R
indices ‰I . 2sꢀI†Š : R1ˆ0.0411,
wR2ˆ0.1095, ®nal R1ˆ0.0459, wR2ˆ0.1147 for all data. The crys-
tal structure of 11 was solved by direct methods, shelxs-86 (Shel-
È
drick, G. M., University of Gottingen, 1990), and re®ned by full-
matrix least squares method on F2 using shelxl-93 (Sheldrick, G.
È
M., University of Gottingen, 1993). Data were corrected for Lorentz
and polarisation effects but not for absorption. All hydrogen atoms
were included on calculated positions with isotropic thermal para-
meters 20% larger than the atom to which they were attached. The
nonhydrogen atoms were re®ned anisotropically. Crystallographic
data of 11 were deposited with the Cambridge Crystallographic
Data Centre. CCDC reference number: 144016.
12. (a) Nabeta, K.; Yamamoto, K.; Hashimoto, M.; Koshino, H.;
Funatsuki, K.; Katoh, K. J. Chem. Soc. Chem. Commun. 1998,
È
1485. (b) Konig, G. M.; Wright, A. D. J. Org. Chem. 1997, 62,
3837.
13. Schulz, S.; Messer, C.; Dettner, K. Tetrahedron Lett. 1997, 38,
2077.
10. Zuckerman-Schpector, J.; Monteiro, H. Acta Crystallogr.
1996, C52, 1767.