A convergent, flexible synthesis of 1,3-dienes

Article abstract of DOI:10.1039/b203975c

1,3-Dienes were prepared from 1,4-ketoxanthates, obtained by the radical addition reaction of an S-(2-oxoalkyl) xanthate to a terminal olefin, through the DBU induced thermal elimination of sulfur dioxide from the derived 2-sulfolenes.

Full text of DOI:10.1039/b203975c

A convergent, flexible synthesis of 1,3-dienes
Marie Lusinchi, Trevor V. Stanbury and Samir Z. Zard*
Laboratoire de Synthèse Organique Associé au CNRS, Ecole Polytechnique, Palaiseau, France
Received (in Cambridge, UK) 25th April 2002, Accepted 27th May 2002
First published as an Advance Article on the web 14th June 2002
Table 2 Transformation of xanthates 3 into 2-sulfolenes 4
1,3-Dienes were prepared from 1,4-ketoxanthates, obtained
by the radical addition reaction of an S-(2-oxoalkyl)
xanthate to a terminal olefin, through the DBU induced
thermal elimination of sulfur dioxide from the derived
2-sulfolenes.
The synthesis of 1,3-dienes from substituted 2,5-dihydrothio-
phene-1,1-dioxides (3-sulfolenes) by thermal or photochemical
elimination of sulfur dioxide has been extensively studied.1 The
isomeric 4,5-dihydrothiophene-1,1-dioxides (2-sulfolenes) are
reported to be in equilibrium with 3-sulfolenes under basic
conditions.2 The in situ isomerisation of 2-sulfolenes to
3-sulfolenes followed by thermal extrusion of sulfur dioxide has
been noted but not fully exploited in synthesis because of a lack
of convenient routes to the precursors.3 In this communication
we report a new protocol for the synthesis of substituted
1,3-dienes from 1,4-ketoxanthates by a base induced thermal
elimination of sulfur dioxide from the key intermediate
2-sulfolenes.
Entry
R1, R2 and R3
Isolated yield
1
2
3
4
R1 = Ph; R2 = H; R3 = C6H13
79%
70%
62%
77%
R1 = Ph; R2 = H; R3 = CH2SiMe3
R1 = 2-MeC6H4; R2 = H; R3 = C6H13
R1 = 4-MeOC6H4; R2 = H; R3 = C6H13
5
R1 = 4-MeOC6H4; R2 = H; R3
=
60%
6
7
R1 = 4-BrC6H4; R2 = H; R3 = C6H13
81%
72%
t
R1 = Bu; R2 = H; R3 = (CH2)9OAc
8
R1, R2
=
R3 = C6H13
48%
We have previously reported that various xanthates undergo
a radical addition to olefinic traps with transfer of the xanthate
group.4 In the case of S-(2-oxoalkyl) xanthates 1, the radical
addition to alkenes 2 initiated by a small amount of lauroyl
peroxide in refluxing cyclohexane produces 1,4-ketoxanthates 3
as shown in Table 1. These adducts are in fact ideal
intermediates for the synthesis of 2-sulfolenes: the xanthate
functionality is readily cleaved by the action of ethylenediamine
to give the corresponding thiol which, following a rapid work
up and exposure to trifluoroacetic acid, ring-closes to the
4,5-dihydrothiophene.5 In situ oxidation with m-CPBA (2.05
eq.) finally gives the required 2-sulfolene intermediates 4
(Table 2).
Initially, potassium carbonate, a potassium carbonate/imidazole
mixture, and DBU, using toluene as the solvent, were
investigated as possible bases. Only DBU gave any of the
desired diene 5a. In order to determine whether the base was
essential for the transformation or whether the reaction was
merely a thermal elimination, a control reaction in toluene was
performed (see Table 3 entry 7). The starting material was
recovered unchanged, indicating that DBU is essential for the
thermal extrusion of sulfur dioxide under these reaction
conditions. Of the solvents examined, cyclohexane was found to
give the highest yields. It is interesting to note that DBU was
reported to fail in an attempted isomerisation of a 2-sulfolene
into a 3-sulfolene.3b
With a good access to 2-sulfolenes in hand, we searched for
suitable experimental conditions enabling their direct conver-
sion into the corresponding 1,3-dienes. The conditions we
explored using sulfolene 4a are summarised in Table 3.
A variety of 2-sulfolenes 4 were subjected to DBU
(1.2–1.3eq) in cyclohexane (ca 0.5 M) at reflux until the
reaction was deemed to be complete by TLC. The results are
compiled in Table 4.
Table 1 Radical transfer reaction of xanthates 1 with olefins 2
Entry
Xanthate R1, R2
Alkene R3
Isolated yield
Table 3 Investigation of conditions for 1,3-diene 5 formation
1
2
3
4
Ph, H
Ph, H
2-CH3C6H4
4-MeOC6H4, H
C6H13
CH2SiMe3
C6H13
84%
72%
68%
92%
Yield
(%)
Entry
Base
Eq.
5.6
1.3
1.2
Time
Solvent
C6H13
1
2
K2CO3
K2CO
Imidazole
DBU
DBU
DBU
3
19
CH3Ph/H2Oa
CH3Pha
0d
0d
5
4-MeOC6H4, H
80%
6
7
4-BrC6H4, H
tBu, H
C6H13
(CH2)9OAc
84%a
74%
3
4
5
6
7
41
1.5
1.5
3
4
5
noneb
23
55
78
52
0d
6.2
1.2
1.0
CH3Phc
Cyclohexanea
EtOHa
8
C6H13
43%
DBU
DBU
—
CH3Pha
a We thank Dr Peter Boutillier for performing this experiment.
a Reflux. b Rt to 90 °C. c 90 °C d Recovered starting material unchanged.
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Table 4 DBU induced thermal elimination of SO2
partners in the initial radical addition step. This intermolecular
addition process brings together the ketone and thiol moieties
necessary for the construction of the desired 2-sulfolene
precursors. We have exploited their base induced isomerisation
to generate dienes, but it is also worth underlining that
2-sulfolenes are in fact vinylic sulfones with a remarkably rich
chemistry of their own.6
Entry
R1, R2 and R3
Isolated yield
1
2
3
4
R1 = Ph; R2 = H; R3 = C6H13
61%
69%
85%
78%
R1 = Ph; R2 = H; R3 = CH2SiMe3
R1 = 2-MeC6H4; R2 = H; R3 = C6H13
R1 = 4-MeOC6H4; R2 = H; R3 = C6H13
Notes and references
1 W. L. Mock, J. Am. Chem. Soc., 1975, 97, 3666; R. M. Kellogg and W.
L. Prins, J. Org. Chem., 1974, 39, 2366; S. D. Macgregor and D. M.
Lemal, J. Am. Chem. Soc., 1966, 88, 2858; W. L. Mock, J. Am. Chem.
Soc., 1966, 88, 2857. For reviews, see: J. Leonard, A. B. Hague and J. A.
Knight, in Organosulfur Chemistry, Synthetic and Stereochemical
Aspects, ed. P. Page, Academic Press, London, 1997; T. S. Chou and H.
H. Tso, Org. Prep. Proc. Int., 1989, 21, 257.
5
R1 = 4-MeOC6H4; R2 = H, R3
=
45%
6
7
R1 = 4-BrC6H4; R2 = H; R3 = C6H13
63%
0%a
t
R1 = Bu; R2 = H; R3 = (CH2)9OAc
R1, R2
=
R3 = C6H13
64%
2 T.-S. Chou and S.-Y. Chang, J. Org. Chem., 1992, 57, 5015; C. D
Broaddus, J. Am. Chem. Soc., 1966, 88, 3863.
8
a The desired product was obtained in a 42% yield by heating in DBU (2.4
eq.), as the solvent, at 160 °C for 5 h.
3 (a) T.-K. Yang, H.-Y. Chu, D.-S. Lee, Y.-Z. Jiang and T.-S. Chou,
Tetrahedron Lett., 1996, 37, 4537and references there cited; S.-S. P.
Chou and M.-H. Chao, Tetrahedron Lett., 1995, 36, 8825; (c) H. H. Tso,
N.-C. Yang and Y.-M. Chang, J. Chem. Soc., Chem. Commun., 1995,
1349; (d) H. H. Tso, T;-S. Chou and S. C. Hung, J. Chem. Soc., Chem.
Commun., 1987, 1552; (e) S. Sengupta and S. Bhattacharayya, Synth.
Commun., 1996, 26, 231.
4 For reviews, see: S. Z. Zard, in Radicals in Organic Synthesis, ed. P.
Renaud and M. Sibi, Wiley YCH, Weinheim, 2001, p. 90–108S. Z. Zard,
Angew. Chem., Int. Ed. Engl., 1997, 36, 672; B. Quiclet-Sire and S. Z.
Zard, Phosphorus, Sulfur, Silicon, 1999, 153–154, 137.
The thermal elimination of sulfur dioxide from 2,5-dihy-
drothiophenes-1,1-dioxides (3-sulfolenes) is known to occur in
a suprafacial (cis elimination) manner with complete ster-
eoselectivity.1 The literature precedence1 and the preliminary
characterisation of the 1,3 dienes 5 obtained from the general
procedure, indicate that a single isomer, the trans, trans-diene,
is formed following the elimination.
In summary, we have succeeded in implementing a flexible,
convergent route to dienes. Synthetically useful functionality
may be introduced on either or both of the xanthate and olefinic
5 For the synthesis of a dihydrothiophene using xanthate chemistry, see: J.
Boivin, L. Ramos and and S. Z. Zard, Tetrahedron Lett., 1998, 39,
6877.
6 P. L. Fuchs and T. F. Braish, Chem. Rev., 1986, 86, 903.
CHEM. COMMUN., 2002, 1532–1533
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