A new synthetic route to 3,4-bridged 1,6,6aλ4-trithiapentalenes

Article abstract of DOI:10.1055/s-2001-15160

A new synthetic route to 3,4-bridged 1,6,6aλ⁴-trithiapentalenes is developed based on reactions of cyclic ketones with Bredereck's reagent followed by thiolation of keto dienamines with phosphorus pentasulfide or Lawesson's reagent.

Full text of DOI:10.1055/s-2001-15160

LETTER
1129
4
A New Synthetic Route to 3,4-Bridged 1,6,6a -Trithiapentalenes
a
Wei Zhang,* Yewande Henry
Lead Discovery, DuPont Crop Protection, Stine-Haskell Research Center, Newark, DE 19714, USAa
a
Current address: Fluorous Technologies, Inc. 970 William Pitt Way, Pittsburgh, PA 15238, USA
Fax 1-412-826-3053; E-mail: w.zhang@fluorous.com
Received 5 April 2001
Table 1
Abstract: A new synthetic route to 3,4-bridged 1,6,6a 4-trithiapen-
talenes is developed based on reactions of cyclic ketones with Bred-
ereck’s reagent followed by thiolation of keto dienamines with
phosphorus pentasulfide or Lawesson’s reagent.
Key words: 1,6,6a 4-Trithiapentalenes, Bredereck’s reagent, phos-
phorus pentasulfide, Lawesson’s reagent
4
1
,6,6a -Trithiapentalenes 1 possess a unique trisulfur-
containing bicyclic ring system. These compounds may
exist as a mixture of degenerate valency tautomers that
rapidly interconvert between the symmetrical formula 1
1
and 1,2-dithiol-3-ylidene thiones 2. The average length
4
of the S-S bond (2.34 Å) found in 1,6,6a -trithiapen-
talenes is distinctly longer than that of a single covalent S-
1
a
S bond (2.08 Å). Between late 1950’s and early 1980’s,
4
the structure and chemical property of 1,6,6a -trithiapen-
talenes were the subject of many studies and discussion.
4
There are several synthetic pathways to 1,6,6a -trithiap-
2
entalenes 1 in the literature. However, the synthetic scope
for 3,4-bridged derivatives 1a is limited, only a few car-
bon bridged compounds have been made by thiolating
3
1
,3,5-triketones or dithiolium salts. In a research project
related to the evaluation of biological activities of 3,4-
bridged trithiapentalenes, we explored other synthetic op-
portunities and discovered a new chemistry as shown in
Scheme 2. Various commercially available cyclic ketones
can be converted to the corresponding trithiapentalenes
within two steps by this reaction process.
The new method is very straightforward. Thus, heating of
a cyclic ketone with 3 to 4 equivs. of bis-dimethylamino-
t-butoxymethane (Bredereck’s Reagent) at 80-110 °C for
4
2
-4 hours gives the keto dienamine 3 in 90-95% yield. At
the key step of thiolation, refluxing of 3 with 1 1.5
equivs. of Lawesson’s reagent leads to the formation of
4
the 3,4-bridged-1,6,6a -trithiapentalene 4. After flash
column chromatgraphy purification of the final product,
the yield for this two-step reaction ranges from 22% to
5
4
9% (Table 1). Similar yields have been obtained by us-
ing P S as the alternative thiolating reagent.
2
5
Scheme 1
Scheme 2
Synlett 2001, No. 7, 1129–1130 ISSN 0936-5214 © Thieme Stuttgart · New York

1
130
W. Zhang, Y. Henry
LETTER
4
Many 3,4-bridged 1,6,6a -trithiapentalenes have been To a solution of 0.85 g (3.0 mmol) of this keto dienamine in 10 mL
of dry benzene was added 1.20 g (3.0 mmol) of Lawesson’s reagent.
The mixture was heated to reflux for 1.5 h. The cooled reaction mix-
prepared by this protocol. The scope of this reaction is
demonstrated by using a broad range of substituted cyclic
ture was filtered. The filtrate was extracted with ethyl acetate. The
or heterocyclic ketones as starting material. The bridged
combined organic layers were washed with 5% NaOH (aq) and
ring size can be varied from five to seven. In addition to
alkyl and aryl groups, substituents such as ester, ketal, and
brine, dried over MgSO , and concentrated in vacuo. The crude
4
product was purified by column chromatography on silica gel (elu-
cyano groups are tolerated. This method is also applied to tion with 20:1, hexanes:ethyl acetate) to give 340 mg (41%) of 10
1
the synthesis of bistrithiapentalene 21. Further extension as a brown solid, mp 106.9-108.4 °C. H NMR (CDCl
)
3.05-3.35
3
1
3
4
(m, 5H), 7.23-7.40 (m, 5H), 8.85 (s, 2H). C NMR (CDCl3) 35.6
to acyclic ketones in the preparation of 1,6,6a -trithiap-
(
2
t, 2C), 38.1 (d), 125.4 (d), 125.5 (d, 2C), 127.3 (d, 2C), 138.1 (s,
entalenes 22-24 is also achieved. The structure of com-
pound 10 is confirmed by an X-ray diffraction study
-
1
C), 142.4 (s), 156.4 (d, 2C), 169.5 (s). IR (neat) 1406 (s) cm . MS
+
m/e (rel. intensity) 277 (M +1, 100).
(
Figure 1). It is noteworthy to mention that compound 10
1
13
is found to be symmetrical by H and C NMR analysis
at room temperature. However, X-ray structure of this In summary, we have developed a general synthetic pro-
compound indicated that the two S-S bonds in compound tacol which provides easy access to various 3,4-bridged-
4
1
0 are not of equal length; one S-S bond distance is 2.409 1,6,6a -trithiapentalenes. The synthetic utility of phos-
Å, while the other one is 2.264 Å.
phorus pentasulfide and Lawesson’s reagent has been ex-
tended.
Acknowledgement
The authors thank William Marshall for providing the X-ray struc-
tural analysis of compound 10.
References and Notes
(
1) For an excellent review, see a) Lozac’h, N. Comprehensive
Heterocyclic Chemistry; Potts, K. T. Ed.; Pergamon: Oxford,
1984, Vol. 6, p1049. See also b) Akiba, K.; Inamoto, N.
Kagaku no Ryoiki, Zokan 1980, 124, 93. c) Beer, R. J. S. Org.
Compd. Sulphur, Selenium, Tellurium 1977, 4, 300. d) Gleiter,
R.; Gygax, R. Top. Curr. Chem. 1976, 63, 49. e) Clark, D. T.
Int. J. Sulfur Chem., Part C 1972, 7, 11.
(
(
2) a) Pogorzelec, P. J.; Reid D. H. J. Chem. Soc. Chem. Commun.
1983, 289. b) Pedersen, C. Th.; Lohse, C. J. Chem. Soc. Perkin
Trans 1 1977, 994.
3) a) Arcoleo, A.; Abbate, G.; Gottuso, M.; Fontana, G.
Heterocycles 1988, 27, 2141. b) Christie, R. M.; Ingram, A.
S.; Reid, D. H.; Webster, R. G. J. Chem. Soc. Perkin Trans 1
1974, 722. c) Dingwall, J. G.; Ingram, A. S.; Reid, D. H.;
Symon, J. D. J. Chem. Soc., Perkin Trans. 1 1973, 2351.
4) a) Abdulla, R. F.; Fuhr, K. H.; Gajewski, R. P.; Suhr, R. G.;
Taylor, H. M.; Unger, P. L. J. Org. Chem. 1980, 45, 1725.
b) Schuda, P. F.; Ebner, C. B.; Morgan, T. M. Tetrahedron
Lett. 1986, 27, 2567.
(
Figure 1 X-Ray Structure of Compound 10
(
5) Keto dienamine 3 can be consumed by reacting with 1-1.5
equivs. of Lawesson’s reagent. Low isolation yield is
probably related to the photoinstability of the product during
flash column chromatography, see ref. 2b.
General procedure for the synthesis of 3,4-bridged 1,6,6a 4-trithia-
pentalenes. Preparation of 10: A mixture of 1.74 g (10 mmol) of
4
-phenylcyclohexanone and 8 mL (38 mmol, 3.8 equivs) of bis-
dimethylamino-t-butoxymethane (Bredereck’s Reagent) was heat-
ed neat at 110 °C for 4 h. The reaction mixture was cooled to room
temperature and water was added. After extraction with ethyl ace-
Article Identifier:
1437-2096,E;2001,0,07,1129,1130,ftx,en;S03601ST.pdf
tate, the combined organic layers were washed with NaHCO (aq.)
3
and brine, dried over MgSO , and concentrated in vacuo. The result-
4
ing crude product was triturated with n-BuCl/hexanes to give 2.70
g (95%) of keto dienamine as a brown solid (mp 158.1-158.7 °C).
Synlett 2001, No. 7, 1129–1130 ISSN 0936-5214 © Thieme Stuttgart · New York