Dialkoxy disulfides from cubycarbinols

Article abstract of DOI:10.1016/S0040-4039(02)02091-9

Two dialkoxy disulfides 2 and 3 have been synthesized in respectable yields. The behaviour of 2 and 3 under thermal and photolytic conditions has been examined and we report the first examples of S₂ liberation from aliphatic dialkoxy disulfides.

Full text of DOI:10.1016/S0040-4039(02)02091-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8781–8784
Dialkoxy disulfides from cubycarbinols
Ronny Priefer, Patrick G. Farrell and David N. Harpp*
Department of Chemistry, McGill University, Montreal, Quebec, Canada H3A 2K6
Received 20 August 2002; accepted 16 September 2002
Abstract—Two dialkoxy disulfides 2 and 3 have been synthesized in respectable yields. The behaviour of 2 and 3 under thermal
and photolytic conditions has been examined and we report the first examples of S2 liberation from aliphatic dialkoxy disulfides.
© 2002 Elsevier Science Ltd. All rights reserved.
Alkoxy disulfides 1 have been known for over a
century1 but only recently have attracted significant
attention2 in spite of a seminal paper by Thompson in
1965.3 Of particular interest is the unusually short SꢀS
ate (4) was hydrolyzed to 4-methoxycarbonyl cubane
carboxylic acid (5)6 and then converted to the 4-iodo-
cubanecarboxylic acid (6) via a Moriarty reaction fol-
lowed by hydrolysis.7 Reduction of 6 with borane
afforded 1-iodo-4-(hydroxymethyl)cubane (7)5b,7 and
with LAH gave cubylcarbinol (8)7 (Scheme 2). Alcohols
7 and 8 were each reacted with 0.5 equiv. of sulfur
monochloride in the presence of Et3N to yield the
corresponding dialkoxy disulfides 2 and 3 (85% and
89% yield.)
,
bond (ca. 1.95 A) in these compounds that raises the
SꢀS bond rotational barrier to ca. 18 kcal/mol2c,d from
the usual barrier of ca. 6–10 kcal/mol in the corre-
sponding disulfides.3,4 In addition, benzylic dialkoxy
disulfides 1 (R=4-X-C6H4) have been shown to decom-
pose smoothly under moderate heat to deliver a
diatomic sulfur fragment that can be trapped by
dienes2f (Scheme 1).
The barrier of rotation for compound 3 was determined
to be 18.7 kcal/mol from the coalescence of the proton
AB quartet at 98°C (aldehyde and alcohol were
detected starting at 90°C.) An accurate value for the
barrier of rotation of 2 could not be obtained due to
the overlap of the AB quartet with the cubyl signal in
Recently we described the successful introduction of a
sulfur atom onto the cubyl framework;4a as part of a
study of the sulfurꢀsulfur bond in dicubyl disulfide and
related structures, we have investigated dialkoxy
disulfides 2 and 3.
1
the H NMR in high boiling solvents.
For nearly 4 decades, Eaton and co-workers have
reported numerous syntheses of variably substituted
cubane derivatives.5 Following these, we have readily
synthesized the two precursor alcohols (7 and 8)6,7 of
the corresponding dialkoxy disulfides in excellent yield.
Commercially available dimethyl 1,4-cubane dicarboxyl-
The crystal structure of bis-(4-iodocubylmethyl)-
dialkoxy disulfide 3 (Fig. 1) revealed no unusual fea-
tures. The OꢀSꢀSꢀO dihedral bond angle is 87.6° and
,
the SꢀS bond length is 1.97 A, which are comparable to
values in other dialkoxy disulfides.8
Scheme 1. Intramolecular fragmentation of dialkoxy disulfides.
* Corresponding author. Tel.: 514-398-6685; fax: 514-398-3797; e-mail: david.harpp@mcgill.ca
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02091-9

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R. Priefer et al. / Tetrahedron Letters 43 (2002) 8781–8784
Scheme 2. Synthetic routes to dialkoxy disulfides from cubylcarbinols. (a) i. 1 equiv. NaOH/MeOH/THF, ii. HCl; (b) i. IBDA,
I2/C6H6, reflux 6 h, ii. NaOH/MeOH, iii. HCl; (c) i. 50 equiv. LAH, THF, reflux 5 days, ii. HCl; (d) i. BH3·SMe2/THF, 0°C, ii.
HCl; (e) S2Cl2, Et3N/CH2Cl2, 0°C.
Figure 1. X-ray structures of bis-(4-iodocubylmethyl)dialkoxy disulfide 3 and bis-cubylmethylsulfite 9.
To date, only benzylic dialkoxy disulfides have been
reported to liberate trappable diatomic sulfur fragments
upon heating. If this decomposition occurs as proposed
in Scheme 1, then it is possible that the relative ease of
abstraction of the benzylic proton accounts for this
moderate-temperature intramolecular rearrangement.
Because of the relatively high s-character of the external
bonds of cubanes,4a,9 we considered it possible that
compounds 2 and 3 might similarly liberate S2 on
thermolysis. Since 2 has a much lower melting point
than 3 (49–51°C compared with 119–121°C), we
expected that it would decompose more rapidly than 3
at a given temperature. This however was not the case
as in refluxing toluene compound 2 is stable for at least
4 days, whereas 3 decomposes completely within 24 h.
Table 1 shows the data obtained for S2 trapping from 2
and 3 with both 2,3-dimethyl and 2,3-diphenyl-1,3-
butadienes.
In general agreement with previous reports,2f,8b a larger
amount of cyclic tetrasulfide than cyclic disulfide was
obtained on heating 2 or 3 with excess 2,3-dimethyl-1,3-
butadiene. However, proportionally more cyclic
disulfide was obtained using excess 2,3-diphenyl-1,3-
butadiene with dialkoxy disulfide 2, in contrast to the
results obtained with 3. In view of the thermal stabili-
ties of the two products obtained from 2,3-diphenyl-

R. Priefer et al. / Tetrahedron Letters 43 (2002) 8781–8784
8783
Table 1. S2 trapping by dienes
1,3-butadiene, no interconversion between them is
probable10 and we have no explanation for the differing
product ratios obtained.
Upon attempted recrystallization of bis-cubylmethyl-
dialkoxy disulfide 211, bis-cubylmethyl-sulfite 9 was
formed (Fig. 1). This was confirmed by X-ray crystal-
lography, followed by independent synthesis.12 It was
also observed that on standing, 2 was eventually com-
pletely converted to 8; thus it was suspected that it
might be light sensitive. Lunazzi and Placucci2e sug-
gested that under photolytic conditions, dialkoxy
’
disulfides undergo homolytic cleavage to give ROS
’
that is quickly oxidized to ROS ꢁO; this species was
then trapped with t-BuNO. When the photolysis was
carried out at −100°C in the absence of a good oxidiz-
ing agent (possibly t-BuNO), sulfite and sulfoxylate
(ROSOR) were detected.2e
We therefore performed two photolysis experiments
with compound 2: one under nitrogen and the other
open to air. After 24 h of irradiation with a sun lamp
(GE-ultraviolet), the sample in the oxygen free environ-
ment contained dialkoxy disulfide, 2, and cubyl-
carbinol, 8 (ꢀ1:1 ratio), whereas the sample that was
open to the atmosphere showed no trace of 2 but
revealed both the sulfite 9 and the alcohol 8 (ꢀ2:3
ratio). The sample that had been under nitrogen was
photolyzed for an additional 24 h after which time it
was completely converted to alcohol 8, as was observed
with the photolyzed sample that was open to the atmo-
sphere for the full 48 h. What this may suggest is that
the dialkoxy disulfide initially becomes oxidized to give
10, followed by SꢀS bond cleavage, affording both
Scheme 3. Proposed photolytic fragmentation of dialkoxy
disulfide, 2.
’
Lunazzi and Placucci have suggested that ROS radi-
cals can lose sulfur easily at temperatures above −100°C
(our reactions were performed at 50°C). Thus, 12 would
likely yield the alkoxy radical (13), that can react with
the more stable sulfinate radical (11) to afford the
sulfite 9; this would eventually be completely converted
to alcohol.
’
’
ROS ꢁO (11) and ROS (12) (Scheme 3).

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R. Priefer et al. / Tetrahedron Letters 43 (2002) 8781–8784
When the photolysis was performed in an inert atmo-
sphere, slower homolytic SꢀS bond cleavage should
take place to form 12, which could lose sulfur to form
the alkoxy radical 13. This might explain why the only
product that we observed in this experiment was cubyl-
carbinol (8). Currently, mechanistic studies are under
way on this class of compounds to deduce their precise
mode of fragmentation.
Tardif, S. L.; Williams, C. R.; Harpp, D. N. J. Am.
Chem. Soc. 1995, 117, 9067.
3. Thompson, Q. E.; Crutchfield, M. M.; Dietrich, M. W.;
Pierron, E. J. Org. Chem. 1965, 30, 2692.
4. (a) Priefer, R.; Lee, Y. J.; Barrios, F.; Wosnick, J. H.;
Lebuis, A.-M.; Farrell, P. G.; Harpp, D. N.; Sun, A.;
Wu, S.; Snyder, J. P. J. Am. Chem. Soc. 2002, 124, 5626;
(b) Fraser, R. R.; Boussard, G.; Saunders, J. K.; Lam-
bert, J. B. J. Am. Chem. Soc. 1971, 93, 3822; (c) Kessler,
H.; Rundel, W. Chem. Ber. 1968, 101, 3350.
5. (a) Emrick, T. S. Ph. D. Dissertation, University of
Chicago, 1997; (b) Eaton, P. E.; Galoppini, E.; Gilardi,
R. J. Am. Chem. Soc. 1994, 116, 7588; (c) Tsanaktsidis,
J.; Eaton, P. E. Tetrahedron Lett. 1989, 30, 6967; (d)
Eaton, P. E.; Yip, Y. C. J. Am. Chem. Soc. 1991, 113,
7692.
In summary, we have prepared the two dialkoxy
disulfides 2 and 3 in good yield. These compounds
represent the first examples of non-benzylic dialkoxy
disulfide that liberate S2 upon heating. In addition, we
have shown that in the presence of oxygen, photolysis
of dialkoxy disulfide 2 yields the precursor alcohol 8,
via sulfite 9.
6. Eaton, P. E.; Nordari, N.; Tsanaktsidis, J.; Upadhyaya,
S. P. Synthesis 1995, 5, 501.
7. Priefer, R.; Farrell, P. G.; Harpp, D. N. Synthesis 2002,
in press.
Acknowledgements
,
8. (a) 85.4° and 1.96 A for (4-NO2-C6H4-CH2-O-S)2 in Ref.
,
2d; (b) 76.8° and 1.93 A for (4-Cl-C6H4-CH2-O-S)2 in
D.N.H. thanks Dr. P. Eaton for helpful discussions,
Drs. A.-M. Lebuis and F. Belanger-Gariepy for X-ray
crystallography data, and NSERC (CDN) for financial
support.
Tardif, S. L. Ph. D. Dissertation, McGill University,
1997.
9. (a) Della, E. E.; Hine, P. T.; Patney, H. K. J. Org. Chem.
1977, 42, 2940; (b) Eaton, P. E.; Cole, T. W., Jr. J. Am.
Chem. Soc. 1964, 86, 3157.
10. Rys, A. Z.; Harpp, D. N. Tetrahedron Lett. 1997, 38,
4931.
References
11. Recrystallization was performed with hexanes and the
dissolved sample was allowed to stand on the bench for 2
days.
1. Legfeld, F. Chem. Ber. 1895, 28, 449.
2. (a) Tardif, S. L.; Harpp, D. N. J. Org. Chem. 2000, 65,
4791; (b) Cerioni, G.; Plumitallo, A. Magnet. Reson.
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12. Cubylcarbinol (8), SO2Cl2, pyridine, CH2Cl2, −10°C, 1 h.
1
mp 94–96°C. H NMR (500 MHz, CDCl3): l 4.05, 4.16
(ABq, J=11.0 Hz, 2H), 4.01 (m, 1H), 3.91 (m, 6H). 13C
NMR (126 MHz, CDCl3): l 62.8, 55.6, 48.5, 47.2, 44.5
ppm. Anal. calcd for C18H18O3S: C, 68.77; H, 5.77;
found: C, 68.58; H, 5.79.