Reaction of a Cyclic Phosphonium Ylide with α,α-Unsaturated Thioesters

Article abstract of DOI:10.1021/jo990528q

The tandem Michael-intramolecular Wittig reactions of a five-membered cyclic phosphonium ylide (2) with α,α-unsaturated thioesters afforded cycloheptene derivatives 4a-g in 29-58% yield. The reaction proceeded via a rigid phosphabicyclic intermediate and supplied the cycloheptene derivatives with high stereoselectivity. On the other hand, although the reaction using S-cyclohexyl cyclopentenethiocarboxylate 5a as a substrate gave a 1:1 mixture of cis and trans adducts of the corresponding hydroazulene derivatives, the reaction of S-tert-butyl cyclopentenethiocarboxylate 5b gave cis-adduct as a major product (cis:trans =17:3).

Full text of DOI:10.1021/jo990528q

5988
J . Org. Chem. 1999, 64, 5988-5992
Rea ction of a Cyclic P h osp h on iu m Ylid e w ith r,â-Un sa tu r a ted
Th ioester s
Narumi Kishimoto, Tetsuya Fujimoto,* and Iwao Yamamoto
Department of Functional Polymer Science, Faculty of Textile Science and Technology,
Shinshu University, Tokida Ueda 386-8567, J apan
Received March 24, 1999
The tandem Michael-intramolecular Wittig reactions of a five-membered cyclic phosphonium ylide
(2) with R,â-unsaturated thioesters afforded cycloheptene derivatives 4a -g in 29-58% yield. The
reaction proceeded via a rigid phosphabicyclic intermediate and supplied the cycloheptene
derivatives with high stereoselectivity. On the other hand, although the reaction using S-cyclohexyl
cyclopentenethiocarboxylate 5a as a substrate gave a 1:1 mixture of cis and trans adducts of the
corresponding hydroazulene derivatives, the reaction of S-tert-butyl cyclopentenethiocarboxylate
5b gave cis-adduct as a major product (cis:trans )17:3).
Ta ble 1. Rea ction of 2 w ith r,â-Un sa tu r a ted th ioester
3a -e
We reported that the reaction of a five-membered cyclic
phosphonium ylide with enones or enoates provided
cycloheptene,1 hydroazulene derivatives,2 or enol ether3
of cycloheptanone derivatives with high stereoselectivity
via tandem Michael-intramolecular Wittig reactions. In
this work, the reaction of the cyclic ylide with R,â-
unsaturated thioesters was attempted in order to in-
crease the versatility of this reaction. Thus far, it is
clarified that the reaction of a phosphonium ylide with
thioesters affords the acyl phosphonium ylide, or in the
intramolecular manner, cyclic vinyl sulfides which can
be introduced to useful compounds such as â-lactam
antibiotics.4 However, as far as we know the reaction of
the ylide with R,â-unsaturated thioester has not been
reported.
The reaction of cyclic phosphonium ylide (2), generated
from the corresponding salt 1 using t-BuOK as a base,
with S-ethyl cinnamthioate 3a was carried out under
several reaction conditions. Although the reaction of the
ylide with 3a in THF both at room temperature (16 h)
and at the boiling point (6 h) afforded the corresponding
cycloheptenyl sulfide 4a in only 13% yield, the same
reaction when refluxed for a prolonged reaction time (44
h) resulted in an increased yield (31%). Moreover, when
this reaction was carried out in refluxing toluene, the
desired product was obtained in 47% yield (Table 1). Acyl
phosphonium salt or an acyclic product stemmed from
the 1,2-addition of the ylide to thioester could not be
isolated. The reaction using NaHMDS as a base did not
improve the yield of the product.
entry
R
thioester time (h) product yield (%)a
1
2
3
4
5
Et
Ph
p-ClC6H4
i-Pr
c-C6H11
3a
3b
3c
3d
3e
47
42
39
40
38
4a
4b
4c
4d
4e
47
29
37
41
58
a
Isolated yield.
enhancement of the yield. The reaction of S-cyclohexyl
thiocarboxylate 3e under the similar reaction conditions
provided the cycloheptene derivative 4e in the highest
yield (58%). The reaction of S-aryl thioate resulted in the
lower yield.
The reaction of the ylide (2) with some S-cyclohexyl
thioates which have a different substituent on the â
carbon atom was also attempted. It was clarified that the
reaction of thioesters having alkyl groups such as Me or
Pr afforded also the corresponding cycloheptenyl sulfides
4f and 4g in 54% and 58% yields (Scheme 1).
In addition, the effect of the substituent on sulfur
atoms in thioesters was examined for the sake of the
The structures of 4a -g were confirmed by 13C NMR,
13C DEPT, and 1H NMR spectroscopy and mass spec-
trometry. Especially, from 13C NMR spectra, the com-
pounds 4a -g were clarified to be a single product because
the peaks ascribed to other stereoisomers were not
detected (Table 2). The intramolecular Wittig reaction
in these reactions was considered to proceed via a similar
rigid phosphabicycle to the reaction using enones or
enoates because the carbons R, â, and γ to phosphorus
had chemical shifts and coupling constants (J PC) very
similar to those in cycloheptene derivatives which were
obtained from the reaction of 2 with enones or enoates.1,3
(1) Fujimoto, T.; Takeuchi, Y.; Kai, K.; Hotei, Y.; Ohta, K.; Yama-
moto, I. J . Chem. Soc., Chem. Commun. 1992, 1263-1264.
(2) Fujimoto, T.; Uchiyama, Y.; Kodama, Y.; Ohta, K.; Yamamoto,
I.; Kakehi, A. J . Org. Chem. 1993, 58, 7322-7323.
(3) Fujimoto, T.; Kodama, Y.; Yamamoto, I. J . Org. Chem. 1997, 62,
6627-6630.
(4) For a review, see: (a) J ohnson, A. W. Ylides and Imines of
Phosphorus; J . Wiley & Sons Inc.: New York, 1993. (b) Murphy, P. J .;
Brennan, J . Chem. Soc. Rev. 1988, 17, 1-30. (c) Becker, K. B.
Tetrahedron 1980, 36, 1717-1745. Recent publications: (d) Hatanaka,
M.; Himeda, Y.; Imashiro, R.; Tanaka, Y.; Ueda, I. J . Org. Chem. 1994,
59, 111-119. (e) Hatanaka, M.; Himeda, Y.; Tanaka, Y.; Ueda, I.
Tetrahedron Lett. 1995, 36, 3211-3214. (f) Greenlee, M. L.; Dininno,
F. P.; Sclzmann, T. N. Heterocycles 1989, 28, 195-202.
10.1021/jo990528q CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/16/1999

Cyclic Phosphonium Ylide-R,â-Unsaturated Thioester Reaction
J . Org. Chem., Vol. 64, No. 16, 1999 5989
Ta ble 2. 13C Ch em ica l Sh ifts a n d 13C-31P Cou p lin g Con sta n ts in Cycloh ep ten e Der iva tives 4a -ga
chemical shifts (ppm) and J PC (Hz)
compd
R1
R2
C1
C2
C3
C6
C7
4a
4b
4c
4d
4e
4f
Ph
Ph
Ph
Ph
Ph
Me
Pr
Et
Ph
42.7 (J PC ) 69.3)
42.4 (J PC ) 69.0)
42.5 (J PC ) 68.9)
42.1 (J PC ) 68.9)
42.8 (J PC ) 69.3)
44.1 (J PC ) 69.3)
42.9 (J PC ) 69.3)
43.2
43.5
43.6
42.6
43.7
31.1
35.8
39.8 (J PC ) 9.3)
39.6 (J PC ) 9.2)
39.7 (J PC ) 8.3)
40.0 (J PC ) 8.8)
40.9 (J PC ) 8.8)
38.8 (J PC ) 3.9)
37.7 (J PC ) 9.8)
30.1 (J PC ) 11.7)
29.9 (J PC ) 9.8)
30.0 (J PC ) 10.3)
28.8 (J PC ) 10.7)
30.0 (J PC ) 11.2)
29.9 (J PC ) 13.2)
29.8 (J PC ) 13.7)
24.3 (J PC ) 1.5)
24.0 (J PC ) 5.5)
24.2 (J PC ) 6.8)
23.7 (J PC ) 1.5)
24.4 (J PC ) 1.5)
23.8
p-ClC6H4
i-Pr
c-C6H11
c-C6H11
c-C6H11
4g
23.6
a
TMS as an internal standard in CDCl3 was employed.
Sch em e 1
Sch em e 3
Sch em e 2
To elucidate if the substituent on the S atom could
affect the stereoselectivity, the reaction of the ylide (2)
with S-tert-butyl cyclopentenethiocarboxylate 5b was
attempted. Consequently, a mixture of two hydroazulene
derivatives 8a and 8b was obtained with a ratio of 3:17
in 54% yield (Scheme 3). Each isomer could be easily
separated by column chromatography, and the same
isomerization as for 6a ,b in CDCl3 was not observed. In
the 13C NMR spectra, signals of the carbons R and δ to
phosphorus of the major product are shifted upfield by
3-5 ppm compared with the minor product. The upfield
shifting of these carbons is considered to be due to the
steric compression effect by reason of a γ-gauche rela-
tionship between R and δ carbon atoms. Accordingly, it
was suggested that the major product would be the cis-
fused hydroazulene derivative. These results could be
supported by the consideration of the transition state in
the intramolecular Wittig reaction. The transition state
in which the five-membered ring is fused to the six-
membered ring in an equatorial-axial manner is thought
to be more favorable than the other possible transition
Accordingly, that trans cycloheptenyl sulfides predomi-
nantly formed was concluded from these points.
On the other hand, the reaction of the ylide 2 with
cyclopentenethiocarboxylate 5a afforded a 1:1 mixture of
two stereoisomers of the corresponding hydroazulene
derivatives in 60% yield (Scheme 2). Although these
isomers were obviously different compounds on TLC and
could be separated by column chromatography, 13C NMR
spectra of each showed the same peaks ascribed to 7 in
which the double bond of the initial product was thought
to be isomerized to the bridgehead position by a trace
amount of acid in chloroform-d. That is to say, it was
clarified that the initial stereoisomers were compounds
6a and 6b which have different configuration at the
bridgehead position adjacent to vinyl sulfide. The 13C
NMR spectra of each compounds in chloroform-d contain-
ing pyridine displayed the corresponding isomers as-
cribed to 6a and 6b.

5990 J . Org. Chem., Vol. 64, No. 16, 1999
Kishimoto et al.
Sch em e 4
Sch em e 6
yield, which was converted9 to 14 by reaction with NaH
in 76% yield (Scheme 6).
Exp er im en ta l Section
Reactions were run in dried glassware under a nitrogen
atmosphere. THF was distilled from sodium benzophenone
ketyl. Toluene was distilled from sodium metal. CH2Cl2 and
DMF were distilled from calcium hydride. Flash column
chromatography was carried out on silica gel 60 (Cica-
MERCK). 1,1-Diphenylphospholanium perchlorate 1 was pre-
pared by the reaction10 of tetraphenyldiphosphine with 1,4-
Sch em e 5
-
-
dibromobutane followed by exchange of Br into ClO4 with
a saturated aqueous NaClO4 solution. The R,â-unsaturated
thioesters were prepared from the reaction of the correspond-
ing acid chlorides with mercaptanes in dry CH2Cl2-pyridine
(1/1). 1H and 13C NMR spectra were recorded on a 90 MHz
spectrometer using CDCl3 as a solvent. Chemical shifts are
reported in δ from TMS as an internal standard. Mass spectra
and HRMS were obtained by EI at 70 eV or FAB. Melting
points are uncorrected.
Gen er a l P r oced u r es for th e Rea ction of Cyclic P h os-
p h on iu m Ylid e 2 w ith Th ioester s 3a -h , 5a , a n d 5b. A
solution of phosphonium salt (0.50 g, 1.47 mmol) and potas-
sium tert-butoxide (0.17 g, 1.52 mmol) in dry toluene (10 mL)
was stirred at room temperature for 30 min. Then a solution
of the thioester (1.50 mmol) in dry toluene (5 mL) was added
dropwise to the mixture, and the resulting solution was
refluxed for 38-47 h. After being cooled to room temperature,
the mixture was quenched with water and extracted with
CH2Cl2. The combined organic layer was washed with water,
dried over Na2SO4, and concentrated under reduced pressure.
The residue was purified by flash column chromatography on
silica gel using AcOEt-CHCl3 (1/1) as eluent.
tr a n s-[4-(Eth ylth io)-2-ph en yl-4-cycloh epten -1-yl]diph en -
ylp h osp h in e Oxid e (4a ). The reaction was performed ac-
cording to the general procedure to give 4a (0.30 g, 47%) as a
white solid: mp 147-150 °C; 1H NMR δ 1.11 (t, J ) 7 Hz,
3H), 2.16-3.08 (m, 10H), 5.54 (brt, 1H), 6.92-7.82 (m, 15H);
IR (KBr) 1180 cm-1 (PdO), 1700 cm-1 (CdC); MS m/z 432 (M+);
HRMS calcd for C27H29OPS 432.1674, found M+ 432.1664.
tr a n s-[4-(P h en ylt h io)-2-p h en yl-4-cycloh ep t en -1-yl]-
d ip h en ylp h osp h in e Oxid e (4b). The reaction was performed
according to the general procedure to give 4b (0.20 g, 29%) as
a white solid.
tr a n s-[4-(p-Ch lor oph en ylth io)-2-ph en yl-4-cycloh epten -
1-yl]d ip h en ylp h osp h in e Oxid e (4c). The reaction was
performed according to the general procedure to give 4c (0.28
g, 37%) as a white solid.
tr a n s-[4-(Isop r op ylth io)-2-p h en yl-4-cycloh ep ten -1-yl]-
d ip h en ylp h osp h in e Oxid e (4d ). The reaction of phospho-
nium salt (0.30 g,0.88 mmol), t-BuOK (0.11 g, 0.97 mmol), and
thioester (0.18 g, 0.88 mmol) in dry toluene (25 mL) was
performed according to the general procedure to give 4d (0.16
g, 41%) as a white solid.
state (equatorial-equatorial manner) because of the 1,2-
diequatorial interaction between the tert-butyl group and
the methylene group in the five-membered ring (Scheme
4). Consequently, the reaction of S-tert-butyl thiocar-
boxylate preferentially afforded the cis-fused hydro-
azulene.
Finally, the sulfur and phosphorus groups in the
hydroazulene derivative 8b were transformed into other
functional groups, which are thought to be useful for
synthesis of naturally occurring products. Although de-
sulfurization of 8b using Raney Ni (W-2)5 gave the
saturated hydroazulene derivative 9, the vinyl sulfone
10 derived from 8b by oxidation6 using mCPBA could be
transformed to the unsaturated hydroazulene 11 by the
reaction of i-PrMgBr7 in the presence of Ni(acac)2 (Scheme
5). This reaction sequence (tandem Michael-Wittig reac-
tion followed by desulfurization) is complementary to the
reaction of the ylide with R,â-unsaturated aldehydes
because the reaction of a cyclic phosphonium ylide with
R,â-unsaturated aldehydes does not give cycloheptene
derivatives but Wittig product.1 In addition, the reaction
of 10 with MeMgBr7 in the presence of Ni(acac)2 provided
the methyl substituted product 12 in 58% yield. More-
over, the reaction8 of 11 with formaldehyde in the
presence of LDA as a base afforded the alcohol 13 in 85%
tr a n s-[4-(Cycloh exylth io)-2-p h en yl-4-cycloh ep ten -1-yl]-
d ip h en ylp h osp h in e Oxid e (4e). The reaction of phospho-
nium salt (0.30 g, 0.88 mmol), t-BuOK (0.11 g, 0.97 mmol),
and thioester (0.22 g,0.88 mmol) in dry toluene (25 mL) was
performed according to the general procedure to give 4e (0.25
g, 58%) as a white solid.
(5) Bratz, M.; Bullock, W. H.; Overman, L. E.; Takemoto, T. J . Am.
Chem. Soc. 1995, 117, 5958-5966.
(6) Hopkins, P. B.; Fuchs, P. L. J . Org. Chem. 1978, 43, 1208-1217.
(7) Fabre, J . L.; J ulia, M.; Verpeaux, J . N. Tetrahedron Lett. 1982,
23, 2469-2472.
(9) Cavalla, D.; Warren, S. Tetrahedron Lett. 1982, 23, 4505-4508.
(10) (a) Muchowski, J . M.; Venuti, M. C. J . Org. Chem. 1981, 46,
459-461. (b) Yamamoto, I.; Fujimoto, T.; Ohta, K.; Matsuzaki, K. J .
Chem. Soc., Perkin Trans. 1 1987, 1537-1539.
(8) Warren, S.; Kennard, O.; Cruse, W. B.; Buss, A. D. J . Chem.
Soc., Perkin Trans. 1 1984, 243-247.

Cyclic Phosphonium Ylide-R,â-Unsaturated Thioester Reaction
J . Org. Chem., Vol. 64, No. 16, 1999 5991
tr a n s-[4-(Cycloh exylth io)-2-m eth yl-4-cycloh ep ten -1-yl]-
d ip h en ylp h osp h in e Oxid e (4f). The reaction of phospho-
nium salt (0.30 g, 0.88 mmol), t-BuOK (0.11 g, 0.97 mmol),
and thioester (0.16 g, 0.88 mmol) in dry toluene (25 mL) was
performed according to the general procedure to give 4f (0.20
g, 54%) as a white solid.
tr a n s-[4-(Cycloh exylth io)-2-p r op yl-4-cycloh ep ten -1-yl]-
d ip h en ylp h osp h in e Oxid e (4g). The reaction of phospho-
nium salt (0.30 g, 0.88 mmol), t-BuOK (0.11 g, 0.97 mmol),
and thioester (0.19 g, 0.88 mmol) in dry toluene (25 mL) was
performed according to the general procedure to give 4g (0.23
g, 58%) as a white solid.
and aromatic carbons; IR (KBr) 1180 cm-1 (PdO), MS m/z 338
(M+); HRMS calcd for C22H27OP 338.1799, found M+ 338.1812.
2-(ter t-Bu tylsu lfon yl)-6-(dip h en ylph osp h in oyl)bicyclo-
[5.3.0]-2-d ecen e (10). To a solution of 8b (0.30 g, 0.71 mmol)
in dry CH2Cl2 (10 mL) immersed in an ice bath was added
85% m-chloroperoxybenzoic acid (0.35 g, 1.70 mmol) at a rate
which caused gentle boiling of the solvent. After the addition,
the ice bath was removed and the solution was stirred for an
additional hour at room temperature. A 20 mL portion of 10%
aqueous sodium sulfite was added, and the mixture was
poured into CH2Cl2. The organic layer was washed with 30
mL of 10% aqueous sodium carbonate and 30 mL of brine,
dried over Na2SO4, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica
gel using AcOEt-CHCl3 (1/1) as eluent. 10: 0.32 g (99%);
2-(Cycloh exylt h io)-6-(d ip h en ylp h osp h in oyl)b icyclo-
[5.3.0]-2-d ecen e (6a a n d 6b). The reaction of phosphonium
salt (0.30 g, 0.88 mmol), t-BuOK (0.11 g, 0.97 mmol), and
thioester (0.19 g, 0.88 mmol) in dry toluene (25 mL) was
performed according to the general procedure to give 6a (0.12
g, 30%) and 6b (0.12 g, 30%) as white solids. 6a : mp 153-
156 °C; 1H NMR (CDCl3 containing pyridine) δ 0.75-2.91 (m,
24H), 5.77 (brs, 1H), 7.31-7.91 (m, 10H); 13C NMR (CDCl3
containing pyridine) δ 24.34, 26.00 (C × 2), 27.01 (2J PC ) 3.4
1
white solid, mp 250-251 °C; H NMR δ 1.25-2.67 (m, 22H),
6.90 (t, J ) 5.1 Hz, 1H), 7.30-7.92 (m, 10H); 13C NMR δ 22.41,
24.05, 24.70, 28.82 (3J PC ) 10.7 Hz), 34.13, 35.05 (3J PC ) 6.3
Hz), 39.92, 41.74 (1J PC ) 69.3 Hz), 45.90 (3J PC ) 7.8 Hz), 61.28,
140.75, 146.16, and aromatic carbons; IR (KBr) 1180 cm-1 (Pd
O), 1700 cm-1 (CdC); MS m/z 456 (M+); HRMS (Fab) calcd for
C
26H34O3PS, M + 1, 457.1966, found, M+ + 1, 457.1953.
Hz), 27.39, 30.72, 33.09, 34.26, 43.32 (2J PC)2.9 Hz), 44.68,
45.28 (1J PC ) 67.8 Hz), 49.82 (3J PC ) 14.7 Hz), and aromatic
carbons; IR (KBr) 1180 cm-1 (PdO); MS m/z 450 (M+); HRMS
(Fab) calcd for C28H36OPS, M + 1, 451.2224, found, M+ + 1,
451.2212. 6b: mp 154.5-156.5 °C; 1H NMR (CDCl3 containing
pyridine) δ 0.59-3.18 (m, 24H), 5.65 (brs, 1H), 7.14-7.82 (m,
10H); 13C NMR (CDCl3 containing pyridine) δ 24.03, 24.36,
26.03 (C × 2), 27.47 (3J PC ) 15.1 Hz), 28.56, 31.85, 33.00, 38.77
6-(Dip h en ylp h osp h in oyl)bicyclo[5.3.0]-2-d ecen e (11).
A solution of i-PrMgBr (3 mL, 0.8 M in dry ether) was added
dropwise to a solution of 10 (0.20 g, 0.44 mmol) and Ni(acac)2
(2 mg) in dry ether (7 mL). The resulting solution was stirred
at room temperature for 20 h. The mixture was acidified by
10% HCl aqueous solution and then extracted with CH2Cl2.
The organic layer was washed with aqueous saturated Na2CO3
and water, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by column chromatography
on silica gel using AcOEt-CHCl3 (1/1) as eluent. 11: 0.12 g
(81%); white solid, mp 187-189 °C; 1H NMR δ 0.94-3.11 (m,
13H), 5.10-5.51 (m, 2H), 7.29-7.96 (m, 10H); 13C NMR δ
22.34, 25.16, 31.53 (3J PC ) 16.6 Hz), 31.83, 32.98, 40.31 (3J PC
) 11.7 Hz), 41.89 (1J PC ) 70.3 Hz), 45.07 (2J PC ) 2.0 Hz),
vinylic carbons and aromatic carbons; IR (KBr) 1180 cm-1 (Pd
O), 1700 cm-1 (CdC); MS (Fab) m/z 337 (M+ + 1); HRMS (Fab)
calcd for C22H26OP, M + 1, 337.1721, found, M+ + 1, 337.1721.
(1J PC ) 71.3 Hz), 43.62 (2J PC ) 2.0 Hz), 44.75, 45.77 (3J PC
)
12.2 Hz), and aromatic carbons; IR (KBr) 1180 cm-1 (PdO);
MS m/z 450 (M+); HRMS (Fab) calcd for C28H36OPS, M + 1,
451.2224, found, M+ + 1, 451.2227.
2-(Cycloh exylt h io)-6-(d ip h en ylp h osp h in oyl)b icyclo-
[5.3.0]-1-d ecen e (7). 7 was recovered from NMR samples of
6a and 6b as a white solid: mp 201-203 °C; 1H NMR δ 0.60-
3.26 (m, 25H), 7.30-8.01 (m, 10H); 13C NMR δ 23.50 (3J PC
)
9.2 Hz), 25.33, 26.03 (C × 2), 26.17, 28.37 (2J PC ) 1.8 Hz),
33.86, 34.13, 34.29, 34.64, 36.41 (3J PC ) 3.7 Hz), 40.93 (1J PC
68.4 Hz), 42.59 (2J PC ) 1.8 Hz), 44.21, 124.82, 149.41 (3J PC
)
)
6-(Dip h e n ylp h osp h in oyl)-2-m e t h ylb icyclo[5.3.0]-2-
d ecen e (12). A solution of MeMgBr (3 mL, 0.8 mol/L in ether)
was added dropwise to a solution of 10 (0.20 g, 0.44 mmol)
and Ni(acac)2 (2 mg) in dry ether (7 mL) by syringe. The
resulting solution was stirred at room temperature for 20 h.
The mixture was acidified by addition of a 10% HCl aqueous
solution and then extracted with CH2Cl2. The organic layer
was washed with aqueous saturated Na2CO3, washed with
water, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by column chromatography
on silica gel using AcOEt-CHCl3 (1/1) as eluent. 12: 90 mg
(58%); white solid, mp 113-115 °C; 1H NMR δ 0.91-3.04 (m,
16H), 5.35 (brs, 1H), 7.31-7.93 (m, 10H); 13C NMR δ 22.32,
23.97, 24.89, 27.15 (3J PC ) 15.3 Hz), 28.04, 31.79 (2J PC )1.8
Hz), 39.57 (1J PC ) 70.8 Hz), 45.07 (2J PC ) 2.4 Hz), 44.45 (3J PC
) 12.2 Hz), 122.08, 136.98, and aromatic carbons; IR (KBr)
11.0 Hz), and aromatic carbons; IR (KBr) 1180 cm-1 (PdO),
1700 cm-1 (CdC); MS m/z 450 (M+); HRMS (Fab) calcd for
C
28H36OPS, M + 1, 451.2224, found, M+ + 1, 451.2234.
2-(ter t-Bu tylth io)-6-(diph en ylph osph in oyl)bicyclo[5.3.0]-
2-d ecen e (8a a n d 8b). The reaction of phosphonium salt (0.30
g, 0.88 mmol), t-BuOK (0.11 g, 0.97 mmol), and thioester (0.16
g, 0.88 mmol) in dry toluene (25 mL) was performed according
to the general procedure to give 8a (0.03 g, 8%) and 8b (0.17
g, 46%) as white solids. 8a : mp 151-154 °C; 1H NMR δ 0.84-
2.88 (m, 22H), 6.30 (brs, 1H), 7.28-7.93 (m, 10H); 13C NMR δ
23.38, 27.02 (2J PC ) 1.8 Hz), 27.33 (3J PC ) 6.1 Hz), 31.45, 33.53,
34.81, 42.61 (2J PC ) 2.4 Hz), 44.40 (1J PC ) 68.4 Hz), 45.78,
51.71 (3J PC ) 13.4 Hz), 137.87, 144.32, and aromatic carbons;
IR (KBr) 1180 cm-1 (PdO), 1700 cm-1 (CdC); MS m/z 424 (M+);
HRMS (Fab) calcd for C26H34OPS, M + 1, 425.2069, found, M+
+ 1, 425.2076. 8b: mp 184-185 °C; 1H NMR δ 0.82-3.18 (m,
22H), 6.21 (brs, 1H), 7.30-7.89 (m, 10H); 13C NMR δ 23.24,
24.19, 28.70 (3J PC ) 15.3 Hz), 30.64, 31.29, 31.96 (3J PC ) 2.4
Hz), 39.14 (1J PC ) 70.8 Hz), 43.46 (2J PC ) 1.8 Hz), 46.32, 46.91
(3J PC ) 11.0 Hz), 135.41, 140.23, and aromatic carbons; IR
(KBr) 1180 cm-1 (PdO), 1720 cm-1 (CdC); MS m/z 424 (M+);
HRMS (Fab) calcd for C26H34OPS, M + 1, 425.2068, found, M+
+ 1, 425.2068.
6-(Dip h en ylp h osp h in oyl)b icyclo[5.3.0]d eca n e (9). A
solution of 8b (0.10 g, 0.24 mmol) in dry ethanol (10 mL) was
added dropwise to Raney Ni (1.67 mL, 0.6 g/mL). The mixture
was stirred at room temperature overnight. Then Raney Ni
was removed by filtration through Celite. The filtrate was
concentrated, and the residue was purified by column chro-
matography on silica gel using AcOEt-CHCl3 (1/1) as eluent.
9: 70 mg (86%); white solid, mp 210-212.5 °C; 1H NMR δ
1.14-2.35 (m, 17H), 7.27-7.92 (m, 10H); 13C NMR δ 22.34,
28.63, 30.47, 31.94 (3J PC ) 14.7 Hz), 32.70 (C × 2), 34.98, 43.17
(2J PC ) 2.0 Hz), 44.56 (3J PC ) 13.2 Hz), 44.51 (1J PC ) 68.4 Hz),
1160 cm-1 (PdO), 1700 cm-1 (CdC); MS (Fab) m/z 351 (M+
+
1); HRMS (Fab) calcd for C23H28OP, M + 1, 351.1878, found,
M+ + 1, 351.1895.
6-(Dip h en ylp h osp h in oyl)-6-(h yd r oxym et h yl)b icyclo-
[5.3.0]-2-d ecen e (13). A solution of 11 (0.25 g, 0.74 mmol) in
dry THF (8 mL) was added dropwise to LDA (5 equiv in dry
THF) at 0 °C. The solution was stirred for 30 min at 0 °C, and
then after warming to room temperature, the mixture was
stirred for 1 h. Gaseous formaldehyde was bubbled until the
solution became yellow color. The resulting solution was
refluxed for 18 h. After being cooled to room temperature, the
mixture was quenched with water and extracted with CH2Cl2.
The combined organic layer was washed with water, dried over
Na2SO4, and concentrated under reduced pressure. The residue
was purified by column chromatography on silica gel using
AcOEt-CHCl3 (1/1) as eluent. 13: 0.23 g (85%); white solid,
mp 140-142 °C; IR (KBr) 1160 cm-1 (PdO), 1640 cm-1 (Cd
C); MS (Fab) m/z 367 (M+ + 1); HRMS (Fab) calcd for
C
23H28O2P, M + 1, 367.1827, found, M+ + 1, 367.1836.

5992 J . Org. Chem., Vol. 64, No. 16, 1999
Kishimoto et al.
6-(Meth ylen e)bicyclo[5.3.0]-2-d ecen e (14). A solution of
13 (0.14 g, 0.38 mmol) in dry DMF (3 mL) was added dropwise
to NaH (60% in oil, 0.026 g, 0.65 mmol), and the resulting
solution was stirred at 60 °C for 16 h. After being cooled to
room temperature, the mixture was quenched with water and
extracted with ether. The combined organic layer was washed
with water, dried over Na2SO4, and concentrated under
reduced pressure. The residue was purified by column chro-
matography on silica gel using n-hexane as eluent. 14: 42.6
mg (76%); colorless liquid; 1H NMR δ 1.16-2.70 (m, 12H),
4.63-4.67 (m, 2H), 5.34-5.38 (m, 2H); 13C NMR δ 23.64, 29.71,
29.95, 34.09, 34.41, 42.32, 49.65, 109.71, 128.11, 134.03,
152.45; IR (KBr) 1640 cm-1 (CdC); HRMS (EI) calcd for C11H16
148.1252, found M+, 148.1247.
Ministry of Education, Science, Sports and Culture of
J apan. We are grateful to Ihara Chemical Co., Ltd., for
a gift of triphenylphosphine. We thank Yoshitomi
Pharmaceutical Co., Ltd., for MS and HRMS measure-
ments. We thank Kissei Pharmaceutical Co., Ltd., for
HRMS measurements.
Su p p or tin g In for m a tion Ava ila ble: Spectral character-
ization of 4b-g and 13C NMR spectra of 4e-g, 6a ,b, 7, 8a ,b,
9-12, and 14. This material is available free of charge via the
Internet at http://pubs.acs.org.
Ack n ow led gm en t. This work was supported in part
by a Grant-in-Aid for COE Research (10CE2003) by the
J O990528Q