Synthesis and structural characterization of cis- and trans-fused 4a,5,6,7,8,8a-hexahydro-2H,4H-1,3-benzodithiines and their 2-methyl and 2,2-dimethyl derivatives

Article abstract of DOI:10.1021/jo011021u

Both cis- and trans-fused 4a,5,6,7,8,8a-hexahydro-2H,4H-1,3-benzodithiine together with their 2-methyl and 2,2-dimethyl derivatives were prepared as racemates from the appropriate dithiols obtained via multistep syntheses. The products were characterized

Full text of DOI:10.1021/jo011021u

1910
J . Org. Chem. 2002, 67, 1910-1917
Syn th esis a n d Str u ctu r a l Ch a r a cter iza tion of Cis- a n d
Tr a n s-F u sed 4a ,5,6,7,8,8a -Hexa h yd r o-2H,4H-1,3-ben zod ith iin es a n d
Th eir 2-Meth yl a n d 2,2-Dim eth yl Der iva tives
Kalevi Pihlaja,*,† Karel D. Klika,† J ari Sinkkonen,† Vladimir V. Ovcharenko,†
Olga Maloshitskaya,† Reijo Sillanpa¨a¨,‡ and J o´zsef Czombos§
Structural Chemistry Group, Department of Chemistry, University of Turku, FIN-20014 Turku, Finland,
Department of Chemistry, University of J yva¨skyla¨, FIN-40500 J yva¨skyla¨, Finland, and Department of
Organic Chemistry, University of Szeged, HUN-6720 Szeged, Hungary
kpihlaja@utu.fi
Received October 22, 2001
Both cis- and trans-fused 4a,5,6,7,8,8a-hexahydro-2H,4H-1,3-benzodithiine together with their
2-methyl and 2,2-dimethyl derivatives were prepared as racemates from the appropriate dithiols
obtained via multistep syntheses. The products were characterized by 1H and 13C NMR, mass
1
spectrometry, and for two of the cis-fused compounds by X-ray diffraction. H,1H vicinal coupling
constants indicated that all compounds attain chair-chair conformations as their predominant
conformations. All three trans-fused isomers exist in totally biased chair-chair conformations and
are essentially conformationally locked, whereas the cis-fused compounds are conformationally
mobile and can potentially attain either the S-in or the S-out conformation. The interconversion of
the conformers is fast on the NMR time-scale at ambient temperatures, but at 213 K 4ar,5,6,7,8,-
8ac-hexahydro-1,3-benzodithiine freezes out into a 83:17 mixture of the S-in and S-out forms,
respectively. Both 2c-methyl-4ar,5,6,7,8,8ac-hexahydro-1,3-dithiine and the dimethyl derivative
adopt almost exclusively the S-in conformer at ambient temperature whereas 2t-methyl-4ar,5,6,7,8,-
8ac-hexahydro-1,3-dithiine is a 5:1 mixture of the S-out and S-in conformers.
In tr od u ction
behavior of even monocyclic systems12 is far from com-
plete, bicyclic decalin systems continue to attract con-
siderable interest with regard to their interesting con-
formational behavior.13 In this vein, we report here a
study on the conformational behavior of cis- and trans-
fused 4a,5,6,7,8,8a-hexahydro-2H,4H-1,3-benzodithiines
and their 2-methyl and 2,2-dimethyl derivatives. Al-
though some substituted derivatives of trans-2-mercap-
tomethyl cyclohexanethiol have been synthesized ear-
lier,14,15 none of the aforementioned compounds have been
previously reported. Starting appropriately either from
diol 1 which is not commercially available but which was
readily prepared applying literature methodology,16 or
compound 2 which was also prepared using specific
literature methods17,18 (see Scheme 1), the polysulfides
The syntheses and spectroscopic analyses (NMR, MS,
and X-ray) of various carbocyclane-fused five- and six-
membered heterocycles have been the subject of intense
and active study over the years and continues to this day
unabated.1,2 For example, cyclohexane-fused 1,3-diox-
anes, first described with regard to their NMR spectros-
copy sometime ago,3 have received recent attention as
part of a fresh study4 on the spectroscopy of (bi)cyclic 1,3-
dioxa compounds. Extending our previous studies of these
and related systems to the 1,3-dithia analogues is a
natural course, and these compounds in their own right
have received considerable attention with regard to
structure,5 conformational analysis,6 thermodynamics,7
and spectroscopy,6,8,9 complementing work on related
compounds such as the 1-thia-10 and 1,4-dithiadecalins.11
Although the full understanding of the conformational
(8) Eliel, E. L.; Bailey, W. F.; Kopp, L. D.; Willer, R. L.; Grant, D.
M.; Bertrand, R.; Christensen, K. A.; Dalling, D. K.; Duch, M. W.;
Wenkert, E.; Schell, F. M.; Cochran, D. W. J . Am. Chem. Soc. 1975,
97, 322.
* Correspondence to Prof. Kalevi Pihlaja, Department of Chemistry,
University of Turku, Vatselankatu 2, FIN-20014 Turku, Finland.
Phone: 358-(2)-3336767. Fax: 358-(2)-3336750.
† University of Turku.
(9) Eliel, E. L.; Rao, V. S.; Riddell, F. G. J . Am. Chem. Soc. 1976,
98, 3583.
(10) Vierhapper, F. W.; Willer, R. L. J . Org. Chem. 1977, 42, 4024.
(11) Rooney, R. P.; Evans, J r., S. A. J . Org. Chem. 1980, 45, 180.
(12) Abraham, R. J .; Ribeiro D. S. J . Chem. Soc., Perkin Trans. 2
2001, 302.
‡ University of J yva¨skyla¨.
§ University of Szeged.
(1) Fu¨lo¨p, F.; Berna´th, G.; Pihlaja K. Adv. Heterocycl. Chem. 1998,
69, 349.
(2) Pihlaja, K.; Kleinpeter, E. In Carbon-13 NMR Chemical Shifts
in Structural and Stereochemical Analysis; Wiley: New York, 1994.
(3) Mattinen, J .; Pihlaja, K.; Czombos, J .; Bartok, M. Tetrahedron
1987, 43, 2761.
(13) Koert, U.; Krauss, R.; Weinig, H.-G.; Heumann, C.; Ziemer, B.;
Mu¨gge, C.; Seydack, M.; Bendig, J . Eur. J . Org. Chem. 2001, 575.
(14) Tschierske, C.; Ko¨hler, H.; Zaschke, H.; Kleinpeter, E. Tetra-
hedron 1989, 45, 6987.
(15) Koehler, H.; Tschierske, C.; Zaschke, H.; Kleinpeter, E. Tetra-
hedron 1990, 46, 4241.
(4) Pihlaja, K.; Nummelin, H.; Klika, K. D.; Czombos, J . Magn.
Reson. Chem. 2001, 39, 657.
(5) Baumeister, U. Acta Crystallogr. C 1990, 46, 1903.
(6) Pihlaja, K.; Bjo¨rkqvist, B. Org. Magn. Reson. 1977, 9, 533.
(7) Da´valos, J . Z.; Flores, H.; J ime´nez, P.; Notario, R.; Roux, M. V.;
J uaristi, E.; Hosmane, R. S.; Liebman, J . F. J . Org. Chem. 1999, 64,
9328.
(16) Fra´ter, Gy. Helv. Chim. Acta 1980, 63, 1383.
(17) (a) Smissman, E. E.; Mode, R. A. J . Am. Chem. Soc. 1957, 79,
3447. (b) Bailey, W. F.; Rivera, A. D.; Zarcone, I. M. J . Synth. Commun.
1987, 17, 1769.
(18) (a) Kova´cs, O¨ .; Schneider, Gy.; Lang, L. K.; Apjok, J . Tetrahe-
dron 1967, 23, 4181. (b) Fodor, G.; Kovacs, O.; To¨mo¨sko¨zi, I.; Szilanyi,
J . Bull. Soc. Chim. Fr. 1957, 357.
10.1021/jo011021u CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/22/2002

4a,5,6,7,8,8a-Hexahydro-2H,4H-1,3-benzodithiines
J . Org. Chem., Vol. 67, No. 6, 2002 1911
Sch em e 1. Th e Rea ction Sch em e Lea d in g to th e Com p ou n d s 9-15 Exa m in ed in Th is Stu d y. Th e
Nu m ber in g System in Use Is Also In d ica ted
3-6 were produced which were subsequently reduced to
the dithiols 7 and 8. From 7 and 8, the dithiines of
interest, 9-15, were readily prepared for this study using
standard acetalization and transacetalization procedures.
The conformations adopted by the compounds were
primarily determined by 1H NMR spectroscopy and were
further examined by 13C NMR, mass spectrometry, and
for comparison in the solid state by single-crystal X-ray
diffraction (for compounds 12 and 13).
by transacetalization from diethyl acetal by treatment
with the dithiol 7. As anticipated, the C-2 epimer of 10
with relative configuration (2c,4ar,8at) was not observed
at all in the reaction products since an axially oriented
methyl group would render it unstable2,19 by ca. 8 kJ
mol-1 relative to 10 leading to a population of less than
5% under equilibrium conditions. Furthermore, kinetic
control appears to favor the formation of the more stable
epimer and equilibration appears to require rather
drastic conditions (cf. 13 and 14, vide infra). All three
trans-fused compounds, 9-11, were produced as race-
mates.
Resu lts a n d Discu ssion
Syn th esis of Tr a n s-F u sed (4a r ,8a t)-Hexa h yd r o-
1,3-d ith iin es (9-11). Starting from commercially avail-
able ethyl cyclohexanone-2-carboxylate (see Scheme 1),
reduction of this racemic ketone using bakers’ yeast16
provided the 1-hydroxyl ester diastereoselectively in good
yield which upon treatment with LiAlH4 provided cis-2-
hydroxymethyl cyclohexanol (1). Ditosylation of this diol
followed by treatment with sodium sulfide and sulfur to
displace the oxygens with sulfur provided a mixture of
two novel bicyclic polysulfides, 3 and 5, the reaction
proceeding with inversion of configuration at C-1. Polysul-
fides 3 and 5 were readily separable by column chroma-
tography and have been characterized by 1H and 13C
NMR and MS. Reduction of either a mixture of the two
or separately provided the trans-2-mercaptomethyl cy-
clohexanethiol (7). The unsubstituted parent trans-fused
hexahydro-1,3-benzodithiine (9) and its 2,2-dimethyl-
substituted derivative (11) were then prepared by stan-
dard acetalization of this trans-dithiol 7 using paraform-
aldehyde or acetone, respectively, under acid-catalyzed
conditions. The 2-methyl derivative (10) with relative
configuration of (2t,4ar,8at) was alternatively obtained
Syn th esis of Cis-F u sed (4a r ,8a t)-Hexa h yd r o-1,3-
d ith iin es (12-15). trans-2-(Hydroxymethyl)cyclohexanol
(2) (prepared using literature methodology17,18) was di-
tosylated followed by treatment with sodium sulfide and
sulfur similarly to 1 to provide a mixture of two cis-fused,
bicyclic polysulfides, 4 and 6 (see Scheme 1). Reduction
of the mixture of the two polysulfides 4 and 6 provided
cis-2-mercaptomethyl cyclohexanethiol (8). The three
compounds 12, 13, and 15 were all readily prepared by
transacetalization from either diethyl formal, diethyl
acetal, or acetone dimethylacetal, respectively, by treat-
ment with the dithiol 8 under acid-catalyzed conditions.
Somewhat surprisingly, the C-2 epimer of 13 with
relative configuration (2t,4ar,8ac) (14) was not isolated
from the reaction of 8 with diethyl acetal and, based on
the significant presence of both the S-in and S-out
conformations for compound 12 (vide infra), it was
expected that 13 and 14 should be of comparable stability
and that 14 should therefore be present to a significant
(19) (a) Pihlaja, K. J . Chem. Soc., Perkin Trans. 2 1974, 890. (b)
Pihlaja, K.; Nikander, H. Acta Chem. Scand. 1977, B31, 265.

1912 J . Org. Chem., Vol. 67, No. 6, 2002
Ta ble 1. 1H Ch em ica l Sh ifts (p p m ) for Com p ou n d s 9-15 a t 298 K
Pihlaja et al.
compound
2ax
2eq
Me-ax
Me-eq
4ax
4eq
4a
5ax
5eq
6ax
6eq
7ax
7eq
8ax
8eq
8a
9
10
11
4.14
4.20
-
4.13
4.22
4.11
4.16
4.19
-
3.41
-
-
3.55
3.20
-
-
-
-
-
-
-
2.55
2.61
2.80
3.16
3.36
3.13
3.43
3.19
3.31
2.53
2.60
2.49
2.70
2.34
2.70
2.42
2.53
2.58
1.69
1.53
1.51
1.95
2.40
1.83
n.d.d
2.19
1.84
1.06
1.04
1.09
2.46
1.69
2.44
n.d.
n.d.
2.38
1.63
1.71
1.72
1.36
1.68
1.26
n.d.
n.d.
1.22
1.40
1.40
1.40
1.36
1.43
1.34
n.d.
n.d.
1.33
1.76
1.79
1.79
1.85
1.46
1.82
n.d.
n.d.
1.79
1.34
1.34
1.36
1.52
1.39
1.54
n.d.
n.d.
1.54
1.76
1.77
1.78
1.46
1.86
1.44
n.d.
n.d.
1.42
1.34
1.34
1.30
1.78
2.15
1.81
2.08
n.d.
1.84
1.75
1.78
1.69
1.78
1.85
1.78
n.d.
n.d.
1.74
2.63
2.64
2.81
3.41
2.87
3.39
2.93
2.99
3.51
1.46
1.55
-
1.82
-
-
-
1.455
-
1.78
12 (S-in)a
12 (S-out)a
13
-
1.49
-
1.46
1.60
14 (S-out)b
14c
15
a
At 213 K. b At 208 K for the 77:23 mixture of epimers 13 and 14. c At 333 K for the 77:23 mixture of epimers 13 and 14, conformationally
d
averaged spectrum of the S-out (78 (2%) and S-in forms (22%). n.d., not detected.
Ta ble 2. 13C Ch em ica l Sh ifts (p p m ) for Com p ou n d s 9-15 a t 298 K
compound
C2
C4
4a
C5
C6
C7
C8
C8a
CH3
9
10
11
32.67
43.02
47.04
36.24
37.59
33.80
43.09
41.83
42.25
34.07
33.52
33.42
26.36
26.44
26.52
26.43
26.31
26.39
32.58
32.0.49
32.15
47.81
48.46
44.29
-
20.54 (eq)
30.51 (eq)
31.45 (ax)
-
12 (S-in)a
12 (S-out)a
13
33.04
24.97
43.91
43.99
43.83
36.10
(35.74)
35.08
37.93
47.10
37.19
27.27
38.45
38.59
38.06
30.17
(30.10)
28.94
34.00
34.35
33.71
35.47
32.94
33.36
32.09
34.96
(34.82)
34.37
36.34
32.79
23.83
34.78
24.05
24.36
23.59
32.22
(31.88)
33.83
25.34
23.94
26.03
19.59
26.37
26.55
25.91
21.56
(21.12)
19.60
26.20
26.07
20.61
27.05
20.91
21.09
20.60
26.19
(26.25)
27.15
23.24
20.98
32.55
27.56
32.60
32.82
32.09
29.92
(29.45)
28.40
32.95
32.08
43.72
40.82
45.27
45.50
44.98
42.19
(42.23)
42.81
40.27
40.62
-
20.91 (eq)
20.94 (eq)
20.93 (eq)
21.13
13b
13 (S-in)c
14b,d,e
(21.34)
14 (S-out)c
14 (S-in)c
15
20.29 (eq)
24.84 (ax)
31.19 (eq)
30.92 (ax)
a
b
At 213 K. At 348 K for the 77:23 mixture of epimers 13 and 14. c At 208 K for the 77:23 mixture of epimers 13 and 14.
Conformationally averaged spectrum of the S-out (77%) and S-in forms (23%). e In parentheses are given the population-weighted average
d
shift values of the S-in and S-out forms of 14 at 208 K based on the conformer ratio of 77:23 at 348 K.
extent at equilibrium. As has been demonstrated earlier,
the equilibration of 1,3-dithianes can be achieved using
either CF3COOH19 or boron trifluoride etherate15,19 at
relatively high temperatures; thus, an NMR sample of
13 treated with a catalytic amount of CF3COOH in CDCl3
at elevated temperatures (200 °C) for an extended period
of time (overnight) yielded an equilibrium mixture con-
sisting of ca. 77 ( 2% 13 and 23 ( 2% 14. Therefore,
equilibrium had not been attained in the synthetic
preparation, and furthermore, kinetic control must have
also been in effect to account for this result. Compound
14 was not isolated but was analyzed from the mixed
solution by 1H and 13C NMR. All four cis-fused com-
pounds, 12-15, were produced as racemates.
ally locked in chair-chair conformations and dynamic
processes were not in effect (see Figure 1). In compound
9, irradiation of the proton resonating at 4.14 ppm
resulted in an enhancement of the H-4ax and H-8a
protons, which indicates that these protons are all axially
orientated. Long-range w-coupling was also observed
between the H-2eq and H-4eq protons of 9, indicating
their stereochemical dispositions and the chair conforma-
tion of the heteroring. In compound 11, irradiation of the
overlapping H-4ax and H-8a protons resulted in an
enhancement of the methyl signal resonating at 1.82
ppm, indicating that this C-2 methyl group is axially
orientated.
Cis-F u sed (4a r ,8a c)-Hexa h yd r o-1,3-d ith iin es. The
unsubstituted parent dithiine 12 provided only broad
Con for m a tion a l An a lysis. Chemical shift assign-
ments were based on the standard application of DQF-
COSY, CHSHF, NOE difference, and HSQC-TOCSY
experiments. In addition, 13C EXSY experiments facili-
tated the ready assignment of the 13C resonances of the
minor conformer of 12 after the assignments of the major
1
signals for both H and 13C NMR at ambient temperature.
At 213 K, coalescence had been traversed and both
conformations gave rise to separate subspectra (see
Tables 1 and 2). Based on the values of the vicinal 1H,1H
coupling constants (Table 3) at this temperature, in
particular the vicinal couplings to the H-4a and H-8a
protons, it was clear that the major conformer (83%) is
the chair-chair S-in conformer and the minor form (17%)
is the chair-chair S-out conformer (see Figure 1). The
increased stability of the latter conformer in comparison
to the corresponding conformers in analogous com-
pounds1 composed of oxygen and/or nitrogen instead of
sulfur is due to the much longer C-S bond which reduces
the diaxial interactions between CH2-4 and H-6ax, and
between CH2-2 and H-8ax (Figure 1). For example, in the
1,3-dioxa analogue no conformational equilibrium was
observed and the O-in conformer predominated3 exclu-
sively as the diaxial interactions are too severe and
1
1
conformer had been made. H chemical shifts and H,1H
coupling constants were extracted using PERCH20 NMR
software. The H and 13C chemical shifts are presented
1
in Tables 1 and 2, respectively. Stereochemical conclu-
1
sions were based on H,1H vicinal coupling constants (see
Table 3) which indicate that all compounds are domi-
nated by chair-chair conformations. The results of NOE
difference experiments supported these conclusions.
Tr an s-Fu sed (4a r ,8at)-Hexah ydr o-1,3-dith iin es. As
expected, these three compounds are each conformation-
(20) see for example, Laatikainen, R.; Niemitz, M.; Weber, U.;
Sundelin, J .; Hassinen, T.; Vepsa¨la¨inen, J . J . Magn. Reson., Ser. A
1996, 120, 1, or the program website at http://www.uku.fi/perch.html.

4a,5,6,7,8,8a-Hexahydro-2H,4H-1,3-benzodithiines
J . Org. Chem., Vol. 67, No. 6, 2002 1913
Ta ble 3. 1H,1H-Cou p lin g Con sta n ts (Hz) for Com p ou n d s 9-15 a t 298 K
compound
2ax,2eq
2eq,4eq
4ax,4eq
4a,4ax
4a,4eq
4a,5eq
4a,5ax
5ax,5eq
5ax,6eq
9
10
11
-13.9
7.0a
-
-13.9
-14.1
7.0a
6.8a
6.9a
-
1.9
-
-13.8
-14.0
-14.4
-14.0
-14.1
-14.1
-13.9
-14.3
-14.4
10.8
10.7
11.4
3.0
12.3
3.2
12.7
10.8
3.3
2.9
3.2
2.9
3.6
3.1
3.6
3.1
3.3
3.8
3.9
3.6
4.0
3.4
2.6
3.2
n.d.f
2.8
3.2
11.9
11.9
11.9
12.0
5.1
12.0
n.d.
5.4
-13.3
-13.3
-13.3
-13.3
-14.9
-13.3
n.d.
3.6
3.4
3.9
3.8
6.9
3.9
n.d.
n.d.
3.9
-
12 (S-in)b
12 (S-out)b
13
2.3
-
-
14 (S-out)c
-
14d
-
n.d.
-13.3
15
-
11.7
5eq,6eq
5ax,6ax
5eq,6ax
6ax,6eq
6ax,7eq
6ax,7ax
6eq,7eq
6eq,7ax
7ax,7eq
9
10
11
2.0
1.5
2.0
3.0
4.8
3.0
n.d.
n.d.
2.5
13.3
13.1
13.0
13.4
12.4
13.2
n.d.
3.2
2.9
3.6
3.8
3.4
-13.1
-13.5
-13.1
-12.7
-15.1e
-13.3
n.d.
4.0
4.4
4.1
3.7
3.9
3.9
n.d.
n.d.
3.8
12.9
12.5
13.1
13.4
11.7
13.2
n.d.
n.d.
13.1
3.2
2.1
2.7
2.2
4.1
2.8
n.d.
n.d.
4.1
3.7
5.1
3.9
4.0
4.6
3.8
n.d.
n.d.
4.0
-14.2
-14.7
-13.7
-14.2
-14.5
-13.6
n.d.
12 (S-in)b
12 (S-out)b
13
4.0
14 (S-out)c
14d
n.d.
n.d.
4.05
n.d.
13.05
n.d.
-13.3
n.d.
-13.5
15
7ax,8eq
7ax,8ax
7eq,8eq
7eq,8ax
8ax,8eq
8a,8ax
8a,8eq
4a,8a
9
10
11
3.7
3.5
3.5
2.4
2.9
3.9
n.d.
n.d.
4.0
13.1
11.7
13.0
14.8
12.7
13.8
12.8
n.d.
13.6
2.3
2.2
2.0
3.5
2.4
3.35
n.d.
n.d.
2.7
4.4
4.2
3.8
2.8
3.4
4.2
3.4
n.d.
4.1
-13.1
-12.6
-13.1
-14.0
-13.9
-14.15
-13.6
-14.0
-14.6
12.1
12.2
12.1
4.7
13.1
4.2
13.1
10.6
4.5
3.6
3.5
3.6
2.0
3.7
2.4
3.5
4.0
2.7
10.1
10.1
10.4
2.3
3.0
3.0
3.5
3.9
3.2
12 (S-in)b
12 (S-out)b
13
14 (S-out)c
14d
15
a
b
d
2ax,2CH3. At 213 K. c At 208 K for the 77:23 mixture of epimers 13 and 14. At 333 K for the 77:23 mixture of epimers 13 and 14,
conformationally averaged spectrum of the S-out (78 (2%) and S-in forms (22%). e Standard deviation (0.4 Hz. f n.d., not detected.
F igu r e 1. The chair-chair conformation adopted by the trans compounds (9-11) and the S-in and S-out conformations adopted
by the cis compounds (12-15) with the axial-axial interactions responsible for the conformational preference and resulting shift
in equilibrium indicated.
completely disfavor the O-out conformer. Based on the
83:17 conformational equilibrium of 12 at 213 K, the S-in
conformer is 2.8 kJ mol-1 more stable than the S-out
conformer.
The synthetic procedure provided only one 2-monom-
ethyl epimer, 13. This molecule also clearly adopts a
biased S-in conformation as indicated by the 1H,1H
coupling constants at ambient temperature, and in this
conformation the 2-methyl substituent is equatorially
orientated. In comparison to 12, the S-in conformation
should be even more favored over the S-out conformation
as the methyl group would change from an equatorial
position in the former to an axial position in the latter.
Upon going down in temperature though, the presence
of another conformer was clearly evident from the
broadening and then resharpening of the signals in both
the 1H and 13C NMR spectra. However, the minor
conformer was not observable at lower temperatures due
to its low concentration which is reduced drastically with
decreasing temperatures. Lacking direct observation of
the minor conformer precludes its explicit identification
since it can be either the S-out conformer (where there
is a large syn-axial interaction between the 2ax-Me and
CH2-8) or the 3,8a-twist form, which for monocyclic 1,3-
dithiane19 is disfavored enthalpy-wise by ca. 16.7 kJ
mol-1 in comparison to the chair form. Using the isomeric

1914 J . Org. Chem., Vol. 67, No. 6, 2002
Pihlaja et al.
2-tert-butyl-2,4-dimethyl-1,3-dithianes (of which one is
completely in the twist form and the other has an axial
2-methyl19) as model compounds whereby ∆HCT ) 20.2
kJ mol-1 and ∆SCT ) 14.3 J K-1 mol-1, it is possible to
estimate that the contribution of the S-in form to 13 at
298 K is ca. 98%, approximating to a 9.6 kJ mol-1
difference in free energy between the two conformers.
This is also borne out by the vicinal 1H,1H coupling
constants (see Table 3) which also provide a value of 98%
for the S-in conformer based on J values taken from 12
for the S-out and S-in conformers. An equilibrium
composed of the S-in and S-out chair-chair forms would
therefore imply that the syn-axial interaction between
the 2-axial methyl and CH2-8 in the latter would be 9.6-
3.2 ) 6.4 kJ mol-1, which in fact is virtually equal to that
between the axial 2-methyl and the axial H-4 and H-8a
hydrogens of the S-in conformer of 14 (vide infra).
Compound 14 at ambient temperature is clearly in a
dynamic equilibrium as evidenced by the breadth of the
difference between the S-out and S-in forms of these
bicyclic 1,3-dithia derivatives and/or small contributions
from twist-boat conformations which are known to be
relatively low energy and also clearly favored by entropy
(vide supra).19 An estimate of the population for the S-in
form of 14 is approximately 12% at 208 K, thus preclud-
1
ing total solution of its H spectrum (in the equilibrium
mixture of the epimers the amount of 14 in total was ca.
23%, i.e., less than 3% of the material weight of the
sample is in the S-in form at 208 K).
By comparison to the previous arguments for 13, the
2,2-dimethyl derivative, 15, should also have its S-out
conformer raised in energy by 9.6 kJ mol-1. In this case,
however, the twist form is excluded since it cannot be
attained without having a pseudoaxial methyl group at
C-2.2 Indeed, the conformational equilibrium is practi-
cally as biased as it is for 13. At ambient temperature
the molecule is almost exclusively in the S-in conforma-
tion as evidenced by the pertinent coupling constants,
but the presence of another conformer was clearly in
evidence upon going down in temperature as the signals
1
signals in the H and 13C NMR. At 208 K, coalescence
had been traversed and both conformations gave rise to
separate subspectra (see Tables 1 and 2). Because the
sample was analyzed as a mixture of compounds (13 and
14) it was difficult to discern the signals of the minor
1
in both the H and 13C NMR spectra first broadened and
then sharpened. However the presence of the minor
conformer was again indiscernible at these lower tem-
peratures as its concentration was again too low for it to
be observed directly. The O-out conformer of the dimethyl
1,3-dioxa analogue was, similarly to the parent 1,3-dioxa
analogue, also severely energetically disfavored.3 How-
ever, the fact that the S-out conformer appears to be
present in this case (15) as the minor conformer in the
dynamic equilibrium supports the conformational equi-
librium existing mainly between the S-in and S-out
chair-chair forms for 13 as well with twist conformations
being of only minor importance in both cases.
1
conformer of 14, particularly in the H NMR spectrum.
Based on the values of the vicinal 1H,1H coupling
constants (Table 3) at this temperature, in particular the
vicinal couplings of the H-4a and H-8a protons, it was
clear that the major conformer is the chair-chair S-out
conformer (cf. 12) which enables an equatorial orientation
of the 2-methyl group and therefore the minor form is
the S-in chair-chair conformation (see Figure 1). Since
the conformational energy of an axial 2-methyl in 1,3-
dithianes2,19 is usually considered to be ca. 8 kJ mol-1
,
Th e 13C NMR ch em ica l sh ifts of com p ou n d s 9-15
are listed in Table 2, and the assignments are based on
the standard application of 2-D experiments. The distinct
13C chemical shifts of the S-in and S-out forms of 12 (an
83:17 mixture at this temperature, respectively) were
obtained below coalescence at 213 K. The chemical shifts
of 13 having the biased S-in conformation with the
equatorial 2-methyl were determined at three tempera-
tures (348, 298, and 208 K). The shift differences between
348 and 208 K vary from less than 0.2 up to 1.3 ppm,
indicating a clear temperature effect. It was possible to
assign the 13C shifts for both the major S-out form with
an equatorial 2-methyl and the minor S-in form with an
axial 2-methyl of 14 at 208 K although several impurity
signals of similar intensity complicated this task in the
case of the latter conformer. The task was made easier
by the fact that the population-weighted average shifts
for the 77:23 mixture of the S-out and S-in forms of 14
at 348 K were also measured (see Table 2). These were
also estimated based on the 13C shifts for the separate
forms at 208 K, and the agreement between the found
and calculated (Table 2) average shifts for 14 at 348 K is
surprisingly good in consideration of the temperature
effects mentioned above.
the S-in conformer of 14 was also expected to be observ-
able to some degree based on an energy difference of 2.8
kJ mol-1 between the two conformers of 12 as this would
place the S-in conformer 5.2 kJ mol-1 in energy above
that of the S-out conformer. However, the interaction of
the axial 2-methyl in the S-in conformation of 14 is not
necessarily equal to that in 1,3-dithianes as there can
exist a palpable entropy difference between the more
stable S-out and the less stable S-in conformer of 14. A
sufficient number of 1H chemical shifts (see Table 1) and
vicinal coupling constants (see Table 3) for the S-out form
of 14 at 208 K were solved and for the conformationally
averaged spectrum at 333 K. Two vicinal coupling
constants at 333 K allow evaluation of the conformational
equilibrium between the S-out and S-in forms, namely
3
3J 4a,4ax ) 10.8 Hz and J 8a,8ax ) 10.6 Hz, both of which
are clearly smaller than the limiting values for the S-out
form of 14 (12.7 and 13.1 Hz, respectively) indicating that
some of the S-in conformer must be present (the respec-
tive model couplings J 4a,4eq and J 8a,8eq from 12 (S-in) are
3.6 and 2.4 Hz). From these values the proportion of the
S-out conformer for 14 at 333 K is calculated to be 78 (
2% and therefore the S-out conformer of 14 is 3.5 kJ
mol-1 more stable than the S-in form at 333 K. Taking
into account that for the unsubstituted cis-fused com-
pound 12 the ratio of the S-in and S-out conformers at
213 K was 83:17 (which corresponds to a free energy
difference of 2.8 kJ mol-1) and assuming that there is no
significant entropy term, the conformational energy of
It was also insightful to compare the 13C chemical shifts
of C-2, C-4, C-4a, and C-8a of 10 and 11 with those
obtained using substituent effects derived for monocyclic
dithianes2 and the parent shifts for 9. For compounds
13-15, the parent shifts are those of the S-in and S-out
forms of 12. In the main, a good or at least satisfactory
agreement was generally forthcoming although in some
cases the ring fusion exhibits, especially for the S-in
an axial 2-methyl in the S-in conformer is 6.3 kJ mol-1
.
This value is somewhat smaller than that for monocyclic
1,3-dithiane and this could be attributed to some entropy

4a,5,6,7,8,8a-Hexahydro-2H,4H-1,3-benzodithiines
J . Org. Chem., Vol. 67, No. 6, 2002 1915
forms, small shift effects which are obviously not present
in the monocyclic alkyl-substituted 1,3-dithianes.2
Ma ss Sp ectr a of Com p ou n d s 9-15. The fragmenta-
tion patterns of compounds 9-13 and 15 under electron
impact were in accord with earlier studies on the
behavior of 2-alkyl- and 2-aryl-1,3-dithianes,21 i.e., frag-
mentation is dominated by the heterocyclic part and not
by any means by the fused carbocycle. The molecular ion
is very strong and often the base peak of the spectrum
(see Table S1, Supporting Information). Very little loss
of H• occurs from 9 and 12 whereas all of the other
compounds yielded strong [M - CH3]+ fragments. The
ion C7H11S2+ is an interesting one; in each case it results
from loss of the C-2 unit of the dithiane ring following a
hydrogen transfer (R1R2C + H, i.e., CH3 from 9 and 12,
C2H5 from 10 and 13, and C3H7 from 11 and 15) and is
consistent with the observations on the monocyclic
dithianes.21c Other common fragments observed were the
[M - HS]+, [M - CH3S]+, and [M - R1R2CS]+• ions. The
loss of HS from the latter ion gave in all cases the
F igu r e 2. The X-ray crystallographic structure of 13. The
adopted conformation in the solid state is the same as the
major conformer adopted in solution (S-in). The cif file of this
structure is available as Supporting Information.
+
abundant ion C7H11 at m/z 95.21
To distinguish cis- and trans-fused isomers a priori
based on their mass spectra is certainly not a trivial
problem, but it can be accomplished.22,23 For 13 and 15
+
the C7H11 ion is the most abundant ion, but for 10 and
11 the relative abundance of this ion was only 66 and
53, respectively. For 9 and 12 the abundances of the [M
- CH3S]+ ion are clearly different, namely 10 vs 43%,
respectively. Thus, there is some indication that a basis
for determining the fusion site stereochemistry exists.
X-r a y Cr ysta l Str u ctu r e Deter m in a tion of 12 a n d
13. 1,3-Dithiane structures do not appear to have been
rigorously examined by X-ray analysis, and there is only
one study5 in the literature that actually reports a
structure which is closely related to the structures
examined here (12 and 13). The solid-state structure of
(2t,4ar,8at)-2-(p-chlorophenyl)-hexahydro-1,3-dithiine (a
phenyl-substituted analogue of compound 10) is unex-
ceptional, and both rings are in near idealized chair
conformations.5 Thus, it provides a reference basis set
for the internal structure of the compounds examined in
this work in terms of bond lengths and bond angles.
Although the compound crystallized in the monoclinic
P21/n space group in comparison to the triclinic P1h space
group for both 12 and 13, the packing of the molecules
indicated little or no intermolecular interactions apart
from van der Waals forces, and this result is translatable
to the two compounds examined here. The primary
interest for these studies was the solid-state conforma-
tional preference of compound 12, and for comparative
purposes the structure of compound 13 was also deter-
mined, which is depicted in Figure 2. Suitable crystals
of 13 amenable for X-ray analysis were obtained without
difficulty from methanol solution by slow evaporation,
and the compound crystallized out in the triclinic P1h
space group. Needless to say the enantiomeric molecule
depicted in Figure 2 comprises half the unit cell with the
other enantiomer constituting the other half of the unit
cell. There was a regular arrangement of similarly
F igu r e 3. The unbiased refinement of the X-ray analysis of
12. The overlaid structures result from irregular stacking of
the molecules with two parallel orientations possible. The
enantiomers crystallized separately but within the one unit
cell (P1h space group).
orientated molecules in the crystal lattice and refinement
was obtained uneventfully. Both six-membered rings
each conform to an almost ideal chair conformation, and
the preferred conformation is the same as the predomi-
nant conformer adopted in solution, namely S-in. The
bonding parametersslengths and anglessare unexcep-
tional and are otherwise normal in comparison to (2t,-
4ar,8at)-2-(p-chlorophenyl)-hexahydro-1,3-dithiine.5
Compound 12 was, by comparison, quite problematic
in that suitable crystals were difficult to obtain despite
the variety of solvents (polar, nonpolar, aromatic, etc.),
and even sublimation, that were used to effect crystal-
lization. The propensity of the compound was to form
thin, needlelike crystals emanating from the one central
point and to “twin” excessively, although acceptable
crystals were finally obtained by slow evaporation from
acetonitrile solution. These crystals were similar to the
needlelike crystals grown by sublimation, and X-ray
analysis indicated both to have the same unit cell.
Randomness was also evident at the packing level as the
compound crystallized out in a random manner with
respect to the orientation of the idealized ring planes
about a C2v axis orthogonal to this same plane. By solving
the structure without any prior bias the refinement
yielded the result depicted in Figure 3, and this was the
only acceptable result that could be obtained. The
(21) (a) Bowie, J . H.; White, P. Y. Org. Mass Spectrom. 1972, 5, 317.
(b) Ibid. 2, 1969, 611. (c) Kuosmanen, P. M. Sc. thesis, University of
Turku, 1977.
(22) Pihlaja, K.; Himottu, M.; Ovcharenko, V.; Go¨ndo¨s, G.; Gera,
L.; Berna´th, G. Rapid Commun. Mass Spectrom. 1996, 10, 214.
(23) In Applications of Mass Spectrometry to Organic Stereochem-
istry; Splitter, J . S.; Tureek, F.; VCH: New York, 1994.

1916 J . Org. Chem., Vol. 67, No. 6, 2002
Pihlaja et al.
were acquired with similar conditions as for the 1-D carbon
spectra but with a postacquisition delay time of 3 s.
1
2-D CHSHF (1H-{13C}, optimized on 145 Hz for J HC), HMBC
n
(1H-{13C}, optimized on 8 Hz for J HC), and EXSY spectra (13C
nucleus; 500 ms mixing time) were all acquired in magnitude
mode. DQF-COSY and HSQC-TOCSY (optimized on 145 Hz
1
for J HC; spin lock times, 15-60 ms; proton field strength
attenuated to 8.3 kHz) experiments were both acquired in
phase-sensitive mode. For all 2-D spectra, the spectral widths
and resolution were appropriately optimized from the 1-D
spectra.
Ma ss sp ectr a were acquired on a VG ZabSpec mass
spectrometer operating in the EI+ mode (direct insert probe,
70 eV). Fragmentation routes were confirmed by metastable
ion analysis.
X-r a y structures for compounds 12 and 13 were determined
using essentially the same methodology as described in ref 24
and according to the principles outlined in the references
therein (refs 29-33). Single-crystal data collections were
performed at ambient temperature on
a Rigaku AFC5S
F igu r e 4. The X-ray crystallographic structure of 12. The
adopted conformation in the solid state is the same as the
major conformer adopted in solution (S-in). The cif file of this
structure is available as Supporting Information.
diffractometer using graphite monochromatized Mo KR radia-
tion (λ ) 0.71069 Å). The unit cell parameters were determined
by least-squares refinement of 25 carefully centered reflections.
Data reduction and subsequent calculations were performed
using teXsan for Windows.25 The structures were solved by
direct methods using the SIR92 program26 and full-matrix
least-squares refinements on F2 were performed using the
SHELXL-97 program.27 For compound 12, heavy atoms were
refined anisotropically while hydrogen atoms were included
at fixed distances with fixed displacement parameters from
their host atoms. For compound 13, heavy atoms were refined
with anisotropic displacement parameters while hydrogen
atoms were refined isotropically. Figures were drawn using
Ortep-3 for Windows.28 The crystal data for compounds 12 and
13 are summarized in the Supporting Information together
with the cif files.
Syn th esis. tr a n s-2-(Mer ca p tom eth yl)cycloh exa n eth iol
(7).14,15 Commercially available ethyl cyclohexanone-2-car-
boxylate (Fluka) was stereoselectively reduced using bakers’
yeast16 to the cis-1-hydroxy ester followed by reduction with
LiAlH4 affording cis-2-(hydroxymethyl)cyclohexanol,17,18 1.
Compound 1 was then ditosylated using standard methodol-
ogy,14,15,29 and a solution of this ditosylate (4.04 g, 9.2 mmol
in 10 mL DMF) was added to a stirred suspension of 3.31 g
Na2S‚9H2O (10.2 mmol; freshly recrystallized from 90% aq
ethanol) and 450 mg (10.2 mmol) of sulfur in 15 mL of DMF.
The mixture was heated to 75 °C and stirred for 34 h, poured
into ice-water, extracted with hexane, dried over Na2SO4, and
concentrated.
contributions of each of the two overlaid structures is
approximately equal. Obviously two molecules cannot
occupy the same space, and the solution is a result of
random stacking. If the molecules can stack with only
minimal intermolecular forces in effect, this could lend
itself either to a random disposition of molecules on top
of one another (a systematic or regular stacking arrange-
ment would otherwise lend itself to refinement) but with
only two possible orientations related by a 2-fold axis, or
to a regular stacking in the column that with additional
molecules becomes increasingly lopsided which is cor-
rected at irregular intervals by a reversal of orientation
of an incoming molecule. Both possible explanations
imply a minimal level of intermolecular interaction not
only between adjacent stacked molecules, but also be-
tween columns of molecules. Depicted in Figure 4 is the
crystal structure of one molecule of 12. The depiction is
enantiomeric, and this moiety comprises one-half of the
unit cell with the other enantiomer comprising the other
half (triclinic P1h space group). This is also true for the
overlaid refinements, i.e., both enantiomers do not appear
to cocrystallize in the one column. Again both six-
membered rings each conform to an almost ideal chair
conformation, and the preferred conformation is the same
as the predominant conformer adopted in solution,
namely S-in. Similarly too, the bonding parameterss
lengths and anglessare unexceptional and are otherwise
normal in comparison to both 13 and (2t,4ar,8at)-2-(p-
chlorophenyl)-hexahydro-1,3-dithiine.5
Column chromatography (silica gel, gradient elution with
hexane/hexane-ether 10:1) afforded the novel bicyclic disul-
fide trans-1,2-dithiahydrindane, 3 (420 mg, 28% yield), as a
yellow oil. HRMS: M+•, 160.0377; calcd for C7H12S2, 160.0380.
1H NMR (CDCl3) δ ppm: 3.34 (dd, 1H, J ) 9.6, J ) 7.1, Heq
-
CHS), 2.89 (ddd, 1H, J ) 11.8, J ) 10.8, J ) 3.7, Hax-CS),
2.75 (dd, 1H, J ) 10.7, J ) 9.6, Hax-CHS), 2.21-2.09 (m, 2H),
1.95-1.10 (m, 7H). MS (EI, 70 eV): 160 (M+•, 35), 95 (100), 67
(23), 55 (8), 41 (11). The novel bicyclic trisulfide trans-1,2,3-
trithiadecalin, 5 (290 mg, 15% yield), was obtained as a white
solid. Mp 66 °C. HRMS: M+•, 192.0101; calcd for C7H12S3,
192.0101. 1H NMR (CDCl3) δ ppm: 3.13-3.05 (m, 1H, CH-
S), 3.08 (dd, 1H, J ) 14.0, J ) 11.1, Hax-CHS), 2.72 (dd, 1H, J
) 14.0, J ) 2.6, Heq-CHS), 1.90-1.74 (m, 4H), 1.57-1.51 (m,
Exp er im en ta l Section
NMR sp ectr a were acquired on either a J EOL Alpha 500
or J EOL Lambda 400 NMR spectrometer equipped with either
a 5 mm normal configuration tunable probe or a 5 mm inverse
probe operating at 500.16 MHz (or 399.78 MHz) for 1H and
125.78 MHz (or 100.54 MHz) for 13C. Spectra were recorded
at 298 K in CDCl3, or where warranted by dynamic effects,
using variable temperature NMR (208-348 K). Both 1H and
13C spectra were referenced internally to tetramethylsilane (0
ppm for both). For 1-D proton spectra, spin analysis was
performed using PERCH software20 for the extraction of 1H
(24) Liimatainen, J .; Lehtonen, A.; Sillanpa¨a¨ R. Polyhedron 2000,
19, 1133.
(25) TeXsan for Windows. Structure Analysis Software. Molecular
Structure Corporation, TX 77381, 1997.
(26) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Gualiardi, A.;
Burla, M. C.; Polidori, G.; Camalli, M. J . App. Crystallogr. 1994, 27,
435.
(27) Sheldrick, G. M. SHELXL-97. Program for Crystal Structure
Refinement. University of Go¨ttingen, Germany, 1997.
(28) Farrugia, L. J . J . App. Crystallogr. 1997, 30, 565.
(29) Eliel, E. L.; Rao, V. S.; Smith, S.; Hutchins, R. O. J . Org. Chem.
1975, 40, 524.
1
chemical shifts and H,1H coupling constants. NOE difference
measurements were acquired at lower resolution using satura-
tion times of 6-8 s. DEPT 135° and selective INEPT (9 ms
n
soft rectangular pulse; optimized on 5-7 Hz for J HC) spectra

4a,5,6,7,8,8a-Hexahydro-2H,4H-1,3-benzodithiines
J . Org. Chem., Vol. 67, No. 6, 2002 1917
5H). 13C NMR (CDCl3) δ ppm: 26.43, 26.94, 32.49, 34.93, 41.11,
42.81, 53.28. MS (EI, 70 eV): 192 (M+•, 79), 127 (21), 95 (100),
94 (13), 93 (30), 81 (19), 79 (10), 67 (24), 55 (9). The polysulfides
3 and 5 were then reduced with LiAlH4 to afford the dithiol 7
in 60% yield (bp 84-86 °C/2 mmHg; liter.14 114-116 °C/10
mmHg) which was then subsequently used without purifica-
tion for the syntheses of compounds 9-11.
(2t,4ar ,8at)-2-Meth yl-h exah ydr o-1,3-ben zodith iin e (10):
yield 60%; mp 60-61 °C (hexane); HRMS, M+•, 188.0705; calcd
for C9H16S2, 188.0693. NMR and MS results in Tables 1-3 and
4, respectively.
(4a r ,8a c)-Hexa h yd r o-1,3-ben zod ith iin e (12): yield: 60%;
bp 104-110 °C/2 mmHg; mp 81-82 °C (hexane); HRMS, M+•
,
174.0543; calcd for C8H14S2, 174.0537. NMR and MS results
cis-2-(Mer ca p tom eth yl)cycloh exa n eth iol (8). trans-2-
(Hydroxymethyl)cyclohexanol17,18 was first ditosylated to pro-
vide an oily product (yield 70%) which was then further
converted to the cis-dithia analogue using sodium disulfide in
DMF (80 °C, 3 days). Reduction with LiAlH4 in ether provided
the dithiol 7 in 60% yield (based on the ditosylate). Bp 82-84
°C/2 mmHg; purity 99% by GC.
(4a r ,8a t)-Hexa h yd r o-1,3-ben zod ith iin e (9). A mixture of
dithiol 7 (250 mg, 1.5 mmol), paraformaldehyde (270 mg, 9
mmol), and p-toluenesulfonic acid (25 mg, 0.15 mmol) in 5 mL
of toluene was refluxed under nitrogen for 30 min, diluted with
hexane, and then washed consecutively with 2 M NaOH and
water. The organic layer was dried over Na2SO4, concentrated,
and purified by column chromatography (silica gel, gradient
elution with hexane/hexane-CH2Cl2 10:1) to yield 160 mg
(60%) of 9 as white crystals, mp 119 °C. HRMS: M+•, 174.0536;
calcd for C8H14S2, 174.0537. NMR and MS results in Tables
1-3 and 4, respectively.
2,2-Dim et h yl-(4a r ,8a t)-h exa h yd r o-1,3-b en zod it h iin e
(11). A solution of dithiol 7 (180 mg, 1.1 mmol) and p-
toluenesulfonic acid (17 mg, 0.1 mmol) in 5 mL of acetone was
refluxed for 8 h under nitrogen, concentrated, and purified by
column chromatography (silica gel, gradient elution with
hexane/hexane-CH2Cl2 10:1) to yield 140 mg (60%) of 11 as a
clear liquid. HRMS: M+•, 202.0835; calcd for C10H18S2, 202.0850.
NMR and MS results in Tables 1-3 and 4, respectively.
Gen er a l Tr a n sa ceta liza tion P r oced u r e for th e P r ep a -
r a tion of Hexa h yd r o-1,3-ben zod ith iin es 10, 12, 13, a n d
15. 10 mmol of 7 or 8 and 20 mmol of diethyl acetal (or diethyl
formal or acetone dimethylacetal) were dissolved in 30 mL of
benzene followed by a catalytic amount of p-toluenesulfonic
acid. The alcohol that formed was removed slowly by azeotropic
distillation. After the reaction was complete, the residue was
taken up in ether, washed with NaHCO3 solution, and dried
over MgSO4. The crude products were purified by vacuum
distillation followed by recrystallization from hexane.
in Tables 1-3 and 4, respectively.
(2c,4ar ,8ac)-2-Meth yl-h exah ydr o-1,3-ben zodith iin e (13):
yield: 65%; bp 95-96 °C/2 mmHg; mp 65-66 °C (hexane);
purity 95% by GC; HRMS, M+•, 188.0697; calcd for C9H16S2,
188.0693. NMR and MS results in Tables 1-3 and 4, respec-
tively.
(2t,4ar ,8ac)-2-Meth yl-h exah ydr o-1,3-ben zodith iin e (14).
To ca. 15 mg of 13 in ca. 0.8 mL of CDCl3 were added
increasing portions (final amount ca. 2 µL) of CF3CO2H, and
1
the reaction was monitored by H NMR with respect to time
and elevated temperatures. Overnight heating at approxi-
mately 200 °C was found to be necessary to force the reaction
along, resulting in an equilibrium mixture of 13 and 14 (77:
23) being obtained. 14 was not isolated from this mixture, and
the sample was used directly for the NMR measurements, the
results of which are summarized in Tables 1-3.
2,2-Dim et h yl-(4a r ,8a c)-h exa h yd r o-1,3-b en zod it h iin e
(15): yield: 58%; bp 103-105 °C/2 mmHg; mp 43-44 °C
(hexane); HRMS: M+•, 202.0861; calcd for C10H18S2, 202.0850.
NMR and MS results in Tables 1-3 and 4, respectively.
Ackn owledgm en t. Financial support from the Acad-
emy of Finland, grant no. 4284 (K.P.), the National
Committee for Technological Development (OMFB,
Hungary, J .C.), and the Centre for International Mobil-
ity (CIMO, Finland, J .C.) are gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Detailed NMR ex-
perimental conditions, mass spectral data (Table S1), and
X-ray crystallographic data (including the cif files) for com-
pounds 12 and 13 is available free of charge via the Internet
at http://pubs.acs.org.
J O011021U