Reductive opening of thiophthalan: A new route to functionalized sulfur-containing compounds

Full text of DOI:10.1021/jo951773m

J . Org. Chem. 1996, 61, 1859-1862
1859
on the application of the above mentioned arene-
catalyzed lithiation procedure to the reductive opening
of thiophthalan. Thereby, a wide range of functionalized
sulfur-containing molecules have become accessible
through the corresponding sulfurated organolithium
intermediates.
Red u ctive Op en in g of Th iop h th a la n :
A New Rou te To F u n ction a lized
Su lfu r -Con ta in in g Com p ou n d s†
J uan Almena, Francisco Foubelo, and Miguel Yus*
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias,
Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain
Resu lts a n d Discu ssion
Received September 28, 1995
After 30 min, the reaction between thiophthalan (1;
easily prepared from R,R′-dibromo-o-xylene and sodium
sulfide11 ) and an excess of lithium powder (1:18 molar
ratio) and a catalytic amount of DTBB (1:0.1 molar ratio,
5 mol %) in THF at -78 °C led to a solution of dianion
intermediate 2, which when treated with different elec-
trophiles [H2O, D2O, PriCHO, ButCHO, PhCHO, (CH2)4-
CO, PhCOMe] at the same temperature for 15 min and
after hydrolysis with water, yielded the expected func-
tionalized thiols 3a -h . When using carbon dioxide as
the electrophilic reagent, thiolactone 3i was directly
obtained after workup (Scheme 1 and Table 1).
The reaction shown in Scheme 1 has to be performed
at low temperature in order to prepare products 3. As
was already observed in the reductive opening of
phthalan,8g when the temperature was allowed to rise
to 20 °C, a second benzylic lithiation took place. There-
fore after reaction with pivalaldehyde under the reaction
conditions shown above, and after warming the reaction
mixture to room temperature, the new dianion interme-
diate 4 was formed, which reacted with water or deute-
rium oxide, giving products 5. This process was not
studied in depth because the resulting products of type
5 are the same as those already prepared from phthalan.8g
In tr od u ction
Sulfur-containing compounds are important in organic
chemistry in both theoretical and physical applications.1
In the case of sulfur-bearing carbanion derivatives, only
the R-substituted intermediates have been widely used
because of their stability and ready preparation by direct
deprotonation.2 Little chemistry has been reported for
other sulfur-containing carbanions, due to their difficult
synthesis and instability.3 On the other hand, and in
keeping with our continued interest in functionalized
organolithium intermediates and their applications in
organic synthesis,4 we have recently developed a new and
potent lithiation methodology5 using a catalytic amount
of arene [usually naphthalene or 4,4′-di-tert-butylbi-
phenyl (DTBB)] as an electron carrier, which has allowed
us to prepare very reactive lithiated intermediates.
Thus, we could have prepared alkyllithium compounds
from nonhalogenated precursors6 (mesylates,6a sulfates,6b,c
phosphates,6d nitriles,6e thioethers,5 phenylsulfones,6f,g
phenylsulfoxides,6g as well as allylic and benzylic alcohols
or their silylated derivatives6h), very reactive oxygenated
and nitrogenated functionalized organolithium com-
pounds through chlorine-lithium exchange7 or through
reductive opening of saturated heterocycles8 (aziridines,8a,b
azetidines,8c tetrahydrofuran,8d dioxolanes,8e,f phthalan,8g
and isochroman8h) and polylithiated synthons from poly-
chlorinated precursors.9 A recent communication on the
reductive cleavage of thiochroman10 prompts this report
† This paper is dedicated to Professor Robert B. Bates for his
fundamental contributions to carbanion chemistry.
(1) For a monography, see: Organic Sulfur Chemistry; Bernardi,
F.; Csizmadia, I. G.; Mangini, A., Eds.; Elsevier: Amsterdam, 1985.
(2) See, for instance: Bates, R. B.; Ogle, C. A. Carbanion Chemistry;
Springer Verlag: Berlin, 1983; p 17.
(3) (a) Screttas, C. G.; Micha-Screttas, M. J . Org. Chem. 1978, 43,
1064. (b) Screttas, C. G.; Micha-Screttas, M. J . Org. Chem. 1979, 44,
713. (c) Almena, J .; Foubelo, F.; Yus, M. Tetrahedron 1995, 51, 11883.
(4) For a review on functionalized organolithium compounds, see:
Na´jera, C.; Yus, M. Trends Org. Chem. 1991, 2, 155.
(5) Yus, M.; Ramo´n, D. J . J . Chem. Soc., Chem. Commun. 1991, 398.
(6) (a) Guijarro, D.; Manchen˜o, B.; Yus, M. Tetrahedron 1992, 48,
4593. (b) Guijarro, D.; Manchen˜o, B.; Yus, M. Tetrahedron Lett. 1992,
33, 5597. (c) Guijarro, D.; Guillena, G.; Manchen˜o, B.; Yus, M.
Tetrahedron 1994, 50, 3427. (d) Guijarro, D.; Manchen˜o, B.; Yus, M.
Tetrahedron 1994, 50, 8551. (e) Guijarro, D.; Yus, M. Tetrahedron 1994,
50, 3447. (f) Guijarro, D.; Yus, M. Tetrahedron Lett. 1994, 35, 2965.
(g) Alonso, E.; Guijarro, D.; Yus, M. Tetrahedron 1995, 51, 2699. (h)
Alonso, E.; Guijarro, D.; Yus, M. Tetrahedron 1995, 51, 11457.
(7) (a) Yus, M.; Ramo´n, D. J . J . Org. Chem. 1992, 57, 750. (b)
Guijarro, A.; Ramo´n, D. J .; Yus, M. Tetrahedron 1993, 49, 469. (c) Gil,
J . F.; Ramo´n, D. J .; Yus, M. Tetrahedron 1993, 49, 4923. (d) Guijarro,
A.; Yus, M. Tetrahedron Lett. 1993, 34, 3487. (e) Ramo´n, D. J .; Yus,
M. Tetrahedron 1993, 49, 10103. (f) Ramo´n, D. J .; Yus, M. Tetrahedron
1993, 49, 7115. (g) Bachki, A.; Foubelo, F.; Yus, M. Tetrahedron Lett.
1994, 35, 7643.
(8) (a) Almena, J .; Foubelo, F.; Yus, M. Tetrahedron Lett. 1993, 34,
1649. (b) Almena, J .; Foubelo, F.; Yus, M. J . Org. Chem. 1994, 59, 3210.
(c) Almena, J .; Foubelo, F.; Yus, M. Tetrahedron 1994, 50, 5775. (d)
Ramo´n, D. J .; Yus, M. Tetrahedron 1992, 48, 3585. (e) Gil, J . F.; Ramo´n,
D. J .; Yus, M. Tetrahedron 1993, 49, 9535. (f) Gil, J . F.; Ramo´n, D. J .;
Yus, M. Tetrahedron 1994, 50, 3437. (g) Almena, J .; Foubelo, F.; Yus,
M. Tetrahedron 1995, 51, 3351. (h) Almena, J .; Foubelo, F.; Yus, M.
Tetrahedron 1995, 51, 3365.
Of the products 3, we find those corresponding to
carbonyl compound derivatives 3c-h especially interest-
ing, because they can be converted into sulfur-containing
heterocycles. Thus, treatment of compounds 3e-h with
85% phosphoric acid in refluxing toluene gave the
expected thioisochromans 6e-h . Only for the isobutyral-
dehyde or pivalaldehyde derivatives 3c and 3d did we
obtain products resulting from rearrangement processes.
While compound 3c yielded not only the expected product
6c, but also the seven-membered ring 7c, in the case of
starting compound 3d only the rearranged thioisochro-
man derivative 6′d was isolated (Scheme 2 and Table 2).
The preparation of compounds 6 represents a two-step
homologation of the starting precursor thiophthalan (1).
(9) (a) Ramo´n, D. J .; Yus, M. Tetrahedron Lett. 1992, 33, 2217. (b)
Guijarro, A.; Yus, M. Tetrahedron Lett. 1993, 34, 2011. (c) Gomez, C.;
Ramo´n, D. J .; Yus, M. Tetrahedron 1993, 49, 4117. (d) Guijarro, A.;
Yus, M. Tetrahedron Lett. 1994, 35, 253. (e) Guijarro, A.; Yus, M.
Tetrahedron 1994, 50, 7857. (f) Guijarro, A.; Yus, M. Tetrahedron 1994,
50, 13269. (g) Guijarro, A.; Yus, M. Tetrahedron 1995, 51, 231. (h)
Huerta, F. F.; Go´mez, C.; Guijarro, A.; Yus, M. Tetrahedron 1995, 51,
3375.
(10) Cohen, T.; Chen F.; Kulinski, T.; Florio, S.; Capriati, V.
Tetrahedron Lett. 1995, 36, 4459.
(11) (a) King, G.; Higgins, S. J . J . Chem. Soc., Chem. Commun. 1994,
825. (b) Harpp, D. N.; MacDonald, J . G. Tetrahedron Lett. 1984, 25,
703.
0022-3263/96/1961-1859$12.00/0 © 1996 American Chemical Society

1860 J . Org. Chem., Vol. 61, No. 5, 1996
Notes
Sch em e 1
Sch em e 3
Ta ble 1. P r ep a r a tion of Com p ou n d s 3 fr om
Th iop h th a la n 1
product 3a
electrophile
c
entry
E+
no.
E
yield (%)b
Rf
0.18d
0.18d
0.26
0.38
0.21
0.14
0.23
0.27
0.38f
Ta ble 3. P r ep a r a tion of Com p ou n d s 9
1
2
3
4
5
6
7
8
9
H2O
D2O
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
D
89
80e
49
62
42
74
65
51
72
producta
PriCHO
ButCHO
PhCHO
Me2CO
(CH2)4CO
PhCOMe
CO2
PriCHOH
ButCHOH
PhCHOH
Me2COH
(CH2)4COH
PhC(OH)Me
-
starting electrophile
entry material
E+
yield
(%)b Rf
c
no.
9fa Me
9fb Me Me2COH
R
E
1
2
3
4
5
6f
6f
6f
6j
6j
D2O
D
71d 0.20e
Me2CO
CO2
52
67
57
0.22
0.43
0.34
0.17
9fc Me
-
ButCHO
9ja
H
H
ButCHOH
All products 3 were >95% pure (GLC and/or 300 MHz 1H
a
(CH2)4CO 9jb
(CH2)4COH 55
b
NMR). Isolated yield after column chromatography (silica gel,
All products 9 were >95% pure (GLC and/or 300 MHz 1H
a
hexane/ethyl acetate) based on the starting thiophthalan 1. c Silica
b
NMR). Isolated yield after column chromatography (silica gel,
gel, hexane/ethyl acetate: 5/1. Silica gel, hexane. e >90% deu-
d
hexane/ethyl acetate) based on the starting material 6. c Silica gel,
terium from mass spectrum and 75 MHz 13C NMR. f Mp 71-72
d
hexane/ethyl acetate: 5/1. >95% deuterium from mass spectrum
°C (pentane/dichloromethane).
and 75 MHz 13C NMR. e Silica gel, hexane.
Sch em e 2
hydrochloric acid12). Applying the procedure shown in
Scheme 1 to both of these starting materials, the corre-
sponding dianion intermediates 8 were prepared which,
after condensation with different electrophiles [D2O,
ButCHO, Me2CO, (CH2)4CO] and final hydrolysis with
water, led to the expected products 9fa -jb. After
workup, the carbonation of intermediate 8f yielded
thiolactone 9fc directly (Scheme 3 and Table 3).
In the case of hydroxy thiols 9fb and 9jb, cyclization
under acidic conditions (see Scheme 2) was carried out,
thus isolating seven-membered ring thioethers 10.
Ta ble 2. P r ep a r a tion of Com p ou n d s 6
producta
yield (%)b
In conclusion, the chemistry described in this paper
offers an easy and versatile approach to a wide range of
sulfur-containing acyclic and cyclic compounds.
starting
material
entry
no.
Rfc
1
2
3
4
5
6
3c
3d
3e
3f
3g
3h
6c + 7c
6′d e
6e
51 (2:3)
35
97
89
85
0.17d + 0.61
0.38d
0.60
0.66
0.22
0.67
Exp er im en ta l Section
6f
6g
6h
Gen er a l. For general information see reference 8. Starting
material 111 and 6j12 were prepared according to the literature
procedures. High resolution mass spectra were performed at
the corresponding service at the University of Valencia.
P r ep a r a t ion of Com p ou n d s 3 fr om Th iop h t h a la n 1.
Gen er a l P r oced u r e. To a blue suspension of lithium powder
(0.125 g, 18.0 g atoms) and a catalytic amount of 4,4′-di-tert-
butylbiphenyl (0.027 g, 0.10 mmol) in THF (8 mL) at -78 °C
was added thiophthalan (1; 1 mmol) under argon, and the
mixture was stirred for 30 min at the same temperature. The
corresponding electrophile (1.5 g mmol; 0.5 mL in the case of
94
a
All products 6 and 7c were >94% pure (GLC and/or 300 MHz
1H NMR). Isolated yield after column chromatography (silica gel,
b
hexane/ethyl acetate) based on the starting material 3. c Silica gel,
hexane/ethyl acetate: 5/1. Silica gel, hexane. e A ca. 30% of
d
another product of unknown structure was also isolated.
In the last part of this study we considered the
reductive opening of thioisochromans 6f (prepared as
described above) and 6j (easily prepared from 2-phenyl-
ethanethiol and paraformaldehyde in the presence of
(12) Bo¨hme, H.; Tils, L.; Unterhalt, P. Chem. Ber. 1964, 19, 179.

Notes
J . Org. Chem., Vol. 61, No. 5, 1996 1861
H2O or D2O; CO2 was bubbled for 1 h) was added. The mixture
was stirred at the same temperature for 15 min and was
hydrolyzed at -78 °C with water. The resulting mixture was
extracted with ethyl acetate. The organic layer was dried over
anhyd Na2SO4 and evaporated (15 mmHg). The residue was
then purified by column chromatography (silica gel; hexane/ethyl
acetate) to yield pure products 3a -h . When the electrophile
was CO2, after having hydrolyzed the mixture with water at -78
°C it was basified with 2.5 M NaOH and extracted with ethyl
acetate. The aqueous layer was then acidified with 3 M HCl
and extracted with ethyl acetate. The organic layer was dried
over anhyd Na2SO4 and evaporated (15 mmHg). The resulting
residue was purified by column chromatography (silica gel;
hexane/ethyl acetate) to yield pure compounds 3. Yields and Rf
values are included in Table 1; analytical and spectroscopic data
as well as literature references follow.
P r ep a r a tion of Com p ou n d s 5 fr om Th iop h th a la n 1.
Gen er a l P r oced u r e. To a blue suspension of lithium powder
(0.125 g, 18.0 g atoms) and a catalytic amount of 4,4′-di-tert-
butylbiphenyl (0.027 g, 0.10 mmol) in THF (8 mL) at -78 °C
was added thiophthalan (1; 1 mmol) under argon, and the
mixture was stirred for 30 min at the same temperature. The
corresponding electrophile (1.5 mmol) was added. The mixture
was stirred at the same temperature for 15 min, and it was
warmed to 20 °C. The mixture was stirred at 20 °C for 1 h, and
then it was cooled again at -78 °C and a second electrophile
(0.5 mL in the case of H2O or D2O) was added. The mixture
was hydrolyzed with water at the same temperature. The
resulting mixture was extracted with ethyl acetate. The organic
layer was dried over anhyd Na2SO4 and evaporated (15 mmHg).
The residue was then purified by column chromatography (silica
gel; hexane/ethyl acetate) to yield pure products 5a ,b. Com-
pounds 5a and 5b were characterized by comparison of their
spectroscopic data with those described in the literature.8g
P r ep a r a tion of Com p ou n d s 6 a n d 7. Gen er a l P r oce-
d u r e. To a solution of the corresponding mercapto alcohol 3c-h
(1 mmol) in toluene (5 mL) was added 85% phosphoric acid (0.4
mL). The reaction mixture was heated at 120 °C for 1 h, and
then toluene was removed by distillation and the resulting
residue was hydrolyzed with water and extracted with ethyl
acetate. The organic layer was dried over anhyd Na2SO4 and
evaporated (15 mmHg). The resulting residue was purified by
column chromatography (silica gel; hexane/ethyl acetate) and/
or recrystallized to yield pure products 6c, 6e-h , 6′d , and 7c.
Yields and Rf values are included in Table 2; analytical and
spectroscopic data as well as literature references follow.
3,4-Dih yd r o-3-isop r op yl-1H-2-th ia n a p h th a len e (6c): IR
(film) 3020, 3000, 730 cm-1; 1H NMR δ 1.05 (d, J ) 6.7 Hz, 6H),
1.75-1.86 (m, 1H), 2.72-3.02 (m, 3H), 3.73 (s, 2H), 7.14-7.17
(m, 4H); 13C NMR δ 18.8, 20.2, 29.8, 33.4, 34.5, 49.1, 126.2, 126.7,
126.8, 129.1, 136.0, 137.6; MS m/ z 192 (M+, 30%), 149 (100);
HRMS calcd for C12H16S 192.0973, found 192.1020.
1
2-Meth ylben zylm er ca p ta n (3a ):13 IR (film) 2560 cm-1; H
NMR δ 1.62 (t, J ) 7.3 Hz, 1H), 2.37 (s, 3H), 3.69 (d, J ) 7.3
Hz, 2H), 7.13-7.21 (m, 4H); 13C NMR δ 18.9, 26.8, 126.3, 127.3,
128.5, 130.5, 135.7, 139.0; MS m/ z 138 (M+, 2%), 45 (100).
2-(Deu ter iom eth yl)ben zylm er ca p ta n (3b): IR (film) 2540
cm-1 1H NMR δ 1.64 (t, J ) 7.0 Hz, 1H), 2.36-2.38 (m, 2H),
;
3.73 (d, J ) 7.0 Hz, 2H), 7.15-7.24 (m, 4H); 13C NMR δ 18.7 (t,
J CD ) 19.5 Hz), 26.8, 126.4, 127.3, 128.6, 130.6, 135.7, 139.1;
MS m/ z 139 (M+, 47%), 106 (100); HRMS calcd for C8H9DS
139.0566, found 139.0570.
1-[2-(Mer ca p tom eth yl)p h en yl]-3-m eth yl-2-bu ta n ol (3c):
14
1
IR (film) 3700-3100, 2520 cm-1; H NMR δ 1.02 (d, J ) 6.7
Hz, 6H), 1.69-1.85 (m, 3H), 2.69 (dd, J ) 14.0, 10.1 Hz, 1H),
2.90 (dd, J ) 14.0, 3.0 Hz, 1H), 3.36-3.84 (m, 3H), 7.16-7.27
(m, 4H); 13C NMR δ 17.5, 18.7, 26.2, 33.7, 36.9, 77.2, 126.9, 127.4,
129.4, 130.6, 137.0, 139.7; MS m/ z 176 (M+ - H2S, 1%), 104
(100).
1-[2-(Mer ca p t om et h yl)p h en yl]-3,3-d im et h yl-2-b u t a n ol
(3d ):14 IR (film) 3620-3240, 2540 cm-1; 1H NMR δ 1.02 (s, 9H),
1.64 (br s, 1H), 1.77 (t, J ) 7.0 Hz, 1H), 2.63 (dd, J ) 13.8, 10.7
Hz, 1H), 2.95 (dd, J ) 13.8, 2.1 Hz, 1H), 3.45 (dd, J ) 10.7, 2.1
Hz, 1H), 3.74 (dd, J ) 13.1, 7.0 Hz, 1H), 3.81 (dd, J ) 13.1, 7.0
Hz, 1H), 7.13-7.28 (m, 4H); 13C NMR δ 25.7, 26.3, 34.5, 35.1,
80.3, 126.9, 127.4, 129.4, 130.7, 137.6, 139.8; MS m/ z 224 (M+,
0.2%), 104 (100).
2-[2-(Mer ca p tom eth yl)p h en yl]-1-p h en yleth a n ol (3e):14
IR (film) 3700-3100, 2540 cm-1; 1H NMR δ 1.72 (t, J ) 7.0 Hz,
1H), 2.21 (br s, 1H), 3.05 (dd, J ) 14.3, 5.5 Hz, 1H), 3.11 (dd, J
) 14.0, 7.9 Hz, 1H), 3.63-3.77 (m, 2H), 4.94 (dd, J ) 7.9, 5.5
Hz, 1H), 7.13-7.34 (m, 9H); 13C NMR δ 26.2, 42.3, 75.0, 125.7,
127.2, 127.4, 127.6, 128.4, 129.4, 130.9, 135.8, 139.8, 144.0; MS
m/ z 226 (M+ - H2O, 0.5%), 104 (100).
3,4-Dih yd r o-3-p h en yl-1H-2-th ia n a p h th a len e (6e):16 IR
(film) 3040, 3020, 1590, 1570, 1490, 750, 740, 690 cm-1; 1H NMR
δ 3.22 -3.25 (m, 2H), 3.88 (d, J ) 15.1 Hz, 1H), 3.97 (d, J )
15.1 Hz, 1H), 4.21 (dd, J ) 8.6, 5.8 Hz, 1H), 7.11-7.38 (m, 9H);
13C NMR δ 30.9, 38.8, 45.2, 126.4, 126.8, 127.3, 127.4, 127.5,
128.5, 129.4, 134.7, 136.9, 142.7; MS m/ z 226 (M+, 32%), 104
(100).
3,4-Dih yd r o-3,3-d im eth yl-1H-2-th ia n a p h th a len e (6f): IR
(film) 3040, 3000, 1570, 1490, 740, cm-1; 1H NMR δ 1.34 (s, 6H),
2.83 (s, 2H), 3.81 (s, 2H), 7.09-7.22 (m, 4H); 13C NMR δ 29.3,
30.8, 41.7, 45.8, 126.3, 126.5, 127.1, 129.9, 134.1, 136.6; MS m/ z
178 (M+, 42%), 59 (100).
Sp ir o[cyclop en t a n e-3-(3,4-d ih yd r o-1H -2-t h ia n a p h t h a -
1-[2-(Mer ca p tom eth yl)p h en yl]-2-m eth yl-2-p r op a n ol (3f):
1
len e)] (6g): IR (film) 3020, 1560, 730 cm-1; H NMR δ 1.67-
14
IR (film) 3600-3100, 2540 cm-1; 1H NMR δ 1.26 (s, 6H), 1.53
1.82 (m, 8H), 2.93 (s, 2H), 3.83 (s, 2H), 7.06-7.17 (m, 4H); 13C
NMR δ 24.1, 29.6, 40.5, 43.6, 51.7, 126.1, 126.4, 127.4, 129.9,
134.2, 136.9; MS m/ z 205 (M+ + 1, 15%), 204 (M+, 100); HRMS
calcd for C13H16S 204.0973, found 204.0988.
(br s, 1H), 1.71 (t, J ) 7.0 Hz, 1H), 2.89 (s, 2H), 3.87 (d, J )
7.0 Hz, 2H), 7.17-7.33 (m, 4H); 13C NMR δ 26.7, 29.7, 45.0,
71.2, 126.8, 127.1, 129.6, 132.1, 135.2, 140.5; MS m/ z 147 (M+
- H2S-CH3, 1%), 43 (100).
3,4-Dih yd r o-3-m et h yl-3-p h en yl-1H -2-t h ia n a p h t h a len e
1-{[2-(Mer ca p t om et h yl)p h en yl]m et h yl}cyclop en t a n ol
(6h ): IR (film) 3040, 3000, 1590, 1570, 1490, 750, 730, 690 cm-1
;
(3g):14 IR (film) 3600-3120, 2540 cm-1 1H NMR δ 1.60-1.82
;
1H NMR δ 1.66 (s, 3H), 3.23 (d, J ) 16.2 Hz, 1H), 3.50 (m, 3H),
7.02-7.53 (m, 9H); 13C NMR δ 29.9, 31.2, 43.9, 46.7, 126.1, 126.5,
126.6, 126.7, 127.6, 128.1, 129.9, 133.5, 136.1, 145.9; MS m/ z
240 (M+, 44%), 104 (100); HRMS calcd for C16H16S 240.0973,
found 240.0974.
(m, 10H), 3.01 (s, 2H), 3.88 (d, J ) 7.0 Hz, 2H), 7.15-7.31 (m,
4H); 13C NMR δ 23.2, 26.7, 39.6, 42.5, 82.7, 127.0, 127.1, 129.5,
131.6, 135.9, 140.4; MS m/ z 204 (M+ - H2O, 2%), 104 (100).
1-[2-(Mer ca p tom eth yl)p h en yl]-2-ph en yl-2-p r op a n ol (3h ):
14
1
IR (film) 3700-3140, 2540 cm-1; H NMR δ 1.24 (t, J ) 7.0
3,4-Dih yd r o-3-isop r op yl-3-m e t h yl-1H -2-t h ia n a p h t h a -
Hz, 1H), 1.62 (s, 3H), 1.92 (br s, 1H), 3.16 (d, J ) 3.3 Hz, 2H),
3.61 (d, J ) 7.0 Hz, 2H), 6.93-7.38 (m, 9H); 13C NMR δ 26.4,
29.7, 46.2, 74.8, 124.8, 126.7, 126.8, 127.3, 128.1, 129.4, 132.1,
134.3, 140.9, 147.7; MS m/ z 240 (M+ - H2O, 0.2%), 43 (100).
len e (6′d ): IR (film) 3040, 3000, 1490, 740 cm-1 1H NMR δ
;
0.98, 1.05 (2d, J ) 6.7 Hz, 6H), 1.14 (s, 3H), 1.78 (heptet, J )
6.7 Hz, 1H), 2.68 (d, J ) 14.5 Hz, 1H), 2.93 (d, J ) 14.5 Hz, 1H),
3.67 (d, J ) 14.7 Hz, 1H), 3.73 (d, J ) 14.7 Hz, 1H), 7.09-7.23
(m, 4H); 13C NMR δ 17.7, 18.3, 24.4, 29.4, 37.8, 42.0, 51.0, 126.4,
126.5, 126.6, 129.7, 135.8, 137.0; MS m/ z 206 (M+, 18%), 163
(100); HRMS calcd for C13H18S 206.1129, found 206.1134.
3,3-Dim eth yl-1,3,4,5-tetr a h yd r o-2-ben zoth iep in (7c): mp
82-83 °C (pentane/CH2Cl2); IR (KBr) 3000, 730 cm-1; 1H NMR
δ 1.40 (s, 6H), 1.80-1.84 (m, 2H), 2.84-2.87 (m, 2H), 3.72 (s,
2H), 7.10-7.13 (m, 4H); 13C NMR δ 29.6, 30.9, 32.3, 42.5, 44.3,
126.5, 126.9, 127.4, 129.8, 141.7, 142.3; MS m/ z 193 (M+ + 1,
1,4-Dih yd r o-3H-2-th ia ben zop yr a n -3-on e (3i):15 mp 71-72
°C (pentane/CH2Cl2); IR (KBr) 1670 cm-1 1H NMR δ 3.77 (s,
;
2H), 4.20 (s, 2H), 7.17-7.33 (m, 4H); 13C NMR δ 34.1, 49.1, 126.5,
127.3, 128.0, 128.6, 133.6, 134.2, 202.8; MS m/ z 164 (M+, 4%),
45 (100).
(13) Cagniant, P.; Cagniant, P. Mme. Bull. Soc. Chim. Fr. 1961,
2225.
(14) For products 3c-h , 9fb, 9ja -jb was not possible to obtain the
corresponding HRMS due to the low intensity of the M+ signal.
(15) Lemaire, C.; Luxen, A.; Christiaens, L.; Guillaume, M. J .
Heterocycl. Chem. 1983, 20, 811.
(16) Farrington, J . J ., J r., Ph. D. Ann Arbor Univ., 1973; Chem.
Abstr. 1974, 81, 135886m.

1862 J . Org. Chem., Vol. 61, No. 5, 1996
Notes
10%), 192 (M+, 76), 143 (100). Anal. Calcd for C12H16S: C,
74.94; H, 8.39; S, 16.67. Found: C, 74.51; H, 8.72; S, 16.80.
P r ep a r a tion of Com p ou n d s 9. Gen er a l P r oced u r e. To
a blue suspension of lithium powder (0.125 g, 18.0 g atoms) and
a catalytic amount of 4,4′-di-tert-butylbiphenyl (0.027 g, 0.10
mmol) in THF (8 mL) at -78 °C was added the corresponding
thioisochroman (6; 1 mmol) under argon, and the mixture was
stirred for 30 min at the same temperature. The corresponding
electrophile (1.5 mmol; 0.5 mL in the case of H2O or D2O; CO2
was bubbled for 1 h) was added. The mixture was stirred at
the same temperature for 15 min and was hydrolyzed with water
at -78 °C. The resulting mixture was extracted with ethyl
acetate. The organic layer was dried over anhyd Na2SO4 and
evaporated (15 mmHg). The residue was then purified by
column chromatography (silica gel; hexane/ethyl acetate) to yield
pure products 9fa -fb and 9ja -jb. When the electrophile was
CO2, after having hydrolyzed the mixture with water at -78 °C
it was basified with 2.5 M NaOH and extracted with ethyl
acetate. The aqueous layer was then acidified with 3 M HCl
and extracted with ethyl acetate. The organic layer was dried
over anhyd Na2SO4 and evaporated (15 mmHg). The resulting
residue was dissolved in benzene (50 mL), a catalytic amount
of p-toluenesulfonic acid (0.001 g) was added, the mixture was
heated in a 120 °C oil bath temperature (Dean-Stark) for 15 h,
the benzene was removed by distillation, and the resulting
residue was hydrolyzed with a saturated aqueous solution of Na2-
CO3 and extracted with ethyl acetate. The organic layer was
dried over anhyd Na2SO4 and evaporated (15 mmHg). The
residue was then purified by column chromatography (silica gel;
hexane/ethyl acetate) to yield the titled compound 9fc. Yields
and Rf values are included in Table 3; analytical and spectro-
scopic data follow.
1-[2-(2-Mer ca p t oet h yl)p h en yl]-3,3-d im et h yl-2-b u t a n ol
(9ja ):14 IR (film) 3700-3240, 2540 cm-1 ; 1H NMR δ 1.02 (s, 9H),
1.40 (t, J ) 7.8 Hz, 1H), 1.49 (br s, 1H), 2.54 (dd, J ) 13.7, 10.7
Hz, 1H), 2.72-2.99 (m, 5H), 3.41 (dd, J ) 10.7, 1.9 Hz, 1H),
7.17-7.21 (m, 4H); 13C NMR δ 25.4, 25.8, 34.6, 35.0, 37.1, 80.1,
126.6, 126.7, 129.7, 130.5, 137.8, 138.6; MS m/ z 220 (M+ - H2O,
0.2%), 105 (100).
1-{[2-(2-Mer ca p t oet h yl)p h en yl]m et h yl}cyclop en t a n ol
1
(9jb):14 IR (film) 3640-3100, 2540 cm-1; H NMR δ 1.31 (br s,
1H), 1.41 (t, J ) 7.6 Hz, 1H), 1.59-1.80 (m, 8H), 2.74 (q, J )
7.6 Hz, 2H), 2.95 (s, 2H), 3.05 (t, J ) 7.6 Hz, 2H), 7.15-7.26 (m,
4H); 13C NMR δ 23.1, 25.6, 37.3, 39.4, 42.4, 82.8, 126.3, 126.7,
129.5, 131.4, 136.4, 139.2; MS m/ z 204 (M+ - H2O, 0.5%), 105
(100).
P r ep a r a tion of Com p ou n d s 10. Gen er a l P r oced u r e.
The same procedure described above for compounds 6 was used
in this case but starting from products 9fb or 9jb. Yields are
shown under structures 10fb and 10jb; Rf, analytical and
spectroscopic data follow.
1,2,4,5-Tet r a h yd r o-2,2,4,4-t et r a m et h yl-3-b en zot h iep in
(10fb): Rf ) 0.28 (hexane); IR (film) 3040, 3000, 1480, 730 cm-1
;
1H NMR δ 1.27 (s, 12H), 3.16 (s, 4H), 7.03-7.25 (m, 4H); 13C
NMR δ 32.0, 44.3, 51.0, 126.4, 131.0, 138.7; MS m/ z 220 (M+,
43%), 131 (100); HRMS calcd for C14H20S 220.1286, found
220.1289.
S p ir o [c y c lo p e n t a n e -2-(1,3,4,5-t e t r a h y d r o -3-b e n zo -
th iep in )] (10jb): Rf ) 0.13 (hexane); IR (film) 3060, 3020, 1490,
750, 730 cm-1 1H NMR δ 1.51-1.74 (m, 8H), 2.60 (t, J ) 5.3
;
Hz, 2H), 3.15 (t, J ) 5.3 Hz, 2H), 3.17 (s, 2H), 6.94-7.06 (m,
4H); 13C NMR δ 24.1, 28.3, 39.7, 40.0, 51.6, 51.7, 126.0, 126.4,
129.5, 131.2, 138.8, 141.5; MS m/ z 218 (M+, 53%), 118 (100);
HRMS calcd for C14H18S requires M, 218.1129, found 218.1130.
1-[2-(D e u t e r io m e t h y l)p h e n y l]-2-m e t h y l-2-p r o p a n e -
1
th iol (9fa ): IR (film) 2540 cm-1; H NMR δ 1.42 (s, 6H), 1.75
(s, 1H), 2.37 (s, 2H), 2.96 (s, 2H), 7.11-7.24 (m, 4H); 13C NMR
δ 20.4 (t, J CD ) 19.2 Hz), 32.7, 46.0, 47.9, 125.2, 126.6, 130.6,
131.7, 136.3, 137.3; MS m/ z 181 (M+, 19%), 41 (100); HRMS
calcd for C11H15DS 181.1036, found 181.1027.
Ack n ow led gm en t. This work was supported by
DGICYT (nos. PB91-0751 and PB94-1514). J .A. thanks
the Ministerio de Educacio´n y Ciencia of Spain for a
fellowship.
1-[2-(2-Met h yl-2-m er ca p t op r op yl)p h en yl]-2-m et h yl-2-
1
p r op a n ol (9fb):14 IR (film) 3600-3140, 2540 cm-1; H NMR δ
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H (300
MHz) and 13C (75 MHz) NMR spectra of new compounds
lacking microanalyses (3b, 3c, 3d , 3e, 3f, 3g, 3h , 6c, 6f, 6g,
6h , 6′d , 9fa , 9fb, 9fc, 9ja , 9jb, 10fb, 10jb) (38 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
1.20 (s, 6H), 1.38 (s, 6H), 1.59 (br s, 1H), 1.67 (s, 1H), 2.96, 3.07
(2s, 4H), 7.16-7.28 (m, 4H); 13C NMR δ 29.4, 32.7, 45.7, 45.9,
47.6, 71.3, 125.8, 126.3, 131.6, 131.9, 136.9, 137.1; MS m/ z 180
(M+ - C3H6O, 20%), 75 (100).
4,5-Dih yd r o-4,4-d im e t h yl-3-b e n zot h ie p in -2(1H )-on e
(9fc): IR (film) 1650 cm-1; 1H NMR δ 1.46 (s, 6H), 3.23 (s, 2H),
4.05 (s, 2H), 7.00-7.31 (m, 4H); 13C NMR δ 32.5, 46.6, 51.6, 52.9,
127.6, 127.7, 129.6, 130.7, 132.6, 136.5, 197.6; MS m/ z 206 (M+,
13%), 131 (100); HRMS calcd for C12H14OS 206.0765, found
206.0768.
J O951773M