A novel acylative ring cleavage of benzothieno[3,2-b]pyran-4-ols: Application to the synthesis of dibenzothiophenes and fused-ring derivatives

Article abstract of DOI:10.1039/a900730j

The benzothienopyranols 3, readily available from the ketone 1, are transformed to the carbamates 5 on treatment with N,N-dimethylcarbamoyl chloride, subsequent thermal electrocyclisation provides access to dibenzothiophene derivatives 6 and 11-13.

Full text of DOI:10.1039/a900730j

A novel acylative ring cleavage of benzothieno[3,2-b]pyran-4-ols: application to
the synthesis of dibenzothiophenes and fused-ring derivatives
Christopher D. Gabbutt,* John D. Hepworth, B. Mark Heron and Jean-Luc Thomas
Department of Chemistry, University of Hull, Hull, UK HU6 7RX. E-mail: c.d.gabbutt@chem.hull.ac.uk
Received (in Liverpool, UK) 26th January 1999, Accepted 11th February 1999
The benzothienopyranols 3, readily available from the
ketone 1, are transformed to the carbamates 5 on treatment
with N,N-dimethylcarbamoyl chloride, subsequent thermal
electrocyclisation provides access to dibenzothiophene de-
rivatives 6 and 11–13.
NMR spectra of these compounds indicated trans stereo-
chemistry of the alkene moiety.‡
We suggest that the benzothiophenes 5 are formed via initial
O-acylation of 3 followed by elimination to give the pyran 4§
which undergoes electrocyclic ring opening to the dienone 4A.
Subsequent deprotonation followed by O-acylation generates 5.
In accord with this proposal, it has recently been demonstrated
that in solution (CDCl3) 5,5-dimethyl-5H-thieno[3,2-b]pyran is
in equilibrium with its dienone valence tautomer.13
Interestingly this elimination–acylation reaction not only
affords carbamates 5 stereospecifically, but regiospecifically
also. Thus 3f gave 5f (mp 116–118 °C, 85%) exclusively. None
of the terminal alkene 7, arising by deprotonation of the methyl
Dibenzothiophene and its congeners are not only of intrinsic
interest but find applications as intermediates for the synthesis
of dyes, pharmaceuticals, organic conductors and novel hetero-
helicenes1,2 and hydrocarbons.3 Dibenzothiophene and, espe-
cially, its benzologues are also of environmental concern
because of their presence in fossil fuels and their combustion
products.4a,b
The most frequently employed ring syntheses of dibenzothio-
phenes employ Friedel–Crafts related chemistry.5 Routes
involving the benzologation of benzo[b]thiophene by alter-
native means are less common. Thus, cycloadditions to
benzo[b]thiophene-2,3-quinodimethanes6 and Diels–Alder re-
actions of benzothienopyran-2- and 3- ones7 have been
investigated. The photodehydrocyclisation of 1-aryl-
2-(thienyl)ethylenes has proved to be of value for construction
of polycyclic condensed thiophenes.4a,5,8 In contrast, benzannu-
lation of thiophenes, in particular, benzo[b]thiophene, by
thermal electrocyclisations has been much less studied.5
3-Substituted dibenzothiophene-1-carbonitriles are accessible
from a tandem thermal cyclisation–elimination reaction of
2-(3-benzothienyl)-5-(dimethylamino)penta-2,4-dienonitriles.9
More recently, 1-acetoxydibenzothiophenes have been obtained
by thermolysis of 4-(2-benzothienyl)-2,3-disubstituted cyclo-
but-2-enones.10
R1
R2
R1
R2
O
OH
O
i–iii
iv
S
S
S
O
O
OH
1
2
3
R1
R2
O
NMe2
H
O
Cl
:B
O
R1
S
R2
S
4
We now report a novel thermal electrocyclisation–elimina-
tion protocol for the synthesis of dibenzothiophenes in which
the key step involves formation of the carbamates 5 by an
unprecedented acylative ring cleavage of benzothieno[3,2-
b]pyran-4-ols 3 with Me2NCOCl. The pyranols are readily
prepared as shown in Scheme 1.†
4A
NMe2
O
NMe2
R1
O
H
R2
O
O
vi
R1
2-Acetyl-3-hydroxybenzo[b]thiophene 1, accessible in a
single step from thiosalicylic acid,11 was treated with 2 equiv. of
LDA in THF at 240 °C to give a deep red solution of the
dianion. Addition of the appropriate ketone (1 equiv.) followed
by aqueous work-up provided the corresponding b-hydroxy
ketone that was cyclised with methanolic-HCl to the benzothie-
nopyranones 2a–g (62–70%). Subsequent reduction gave 3a–g
in high yield.
Attempts to dehydrate 3a to 4a which, we envisaged, would
function as a Diels–Alder diene, with TsOH in toluene, or with
TsCl or MsCl in pyridine, failed to give a tractable product. The
Chugaev-type elimination via in situ formation of the thiocarbo-
nate from PhOCSCl was also unsuccessful. A mechanistically
related, though little used, route to alkenes from alcohols
involves the formation of carbamates, (from R2NCOCl–
pyridine), the elimination step being accomplished separately
by flow pyrolysis at ca. 300–500 °C.12 When 3a was heated
with Me2NCOCl in pyridine (ca. 5 h) the anticipated O-acyl
derivative was not obtained, the only isolable product was,
remarkably, 5a (mp 134–135 °C). Yields were optimised (74%)
when 2 equiv. of Me2NCOCl were used. Under the same
conditions 3b–f gave 5b–f in excellent yields (70–90%). The 1H
R2
S
S
5
a
b
c
d
e
f
R1–R2 = (CH2)3
R1–R2 = (CH2)4
R1–R2 = (CH2)5
R1–R2 = (CH2)6
R1–R2 = (CH2)10
R1 = R2 = Me
R1
R2
S
R
1 = H, R2 = Me
6
g
O
NMe2
O
O
S
Me
Me
Et
S
7
8
Scheme 1 Reagents and conditions: i, LDA, THF, 240 °C; ii, R1CH2COR2,
dil. HCl; iii, MeOH–HCl; iv, NaBH4, EtOH; v, Me2NCOCl (2 equiv.),
pyridine, reflux; vi, triethylene glycol, reflux.
Chem. Commun., 1999, 541–542
541

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group in 4Af, was observed.¶ The E,E stereochemistry of 5f was
established from its 1H NMR spectrum and a NOESY
experiment which confirmed the cis disposition of the methyl
groups.
Notes and references
† All new compounds were characterised by 1H and 13C NMR, HRMS and
elemental analysis.
‡ The vicinal alkene protons appeared as doublets at ca. d 6.5 and 6.7, J
16 Hz, (CDCl3) for 5a,b,e and f. However, in 5c,d the signals were
coincidental (d 6.59, 2H, s for both) and trans stereochemistry was assumed
for these compounds by analogy with the other examples.
§ We are unaware of any examples in which carbamoylation with
Me2NCOCl is accompanied by in situ elimination. The nature of the
elimination step (3 to 4) is a matter of conjecture but a pericyclic (syn)
process cannot be excluded. Examples of such non-pyrolytic carbamate
eliminations are rare, but the thermolysis of 1,1,3,4-tetramethyl-3-(phenyl-
carbamoyloxy)-2,3-dihydrosilole (CCl4, D, 10 h) to 1,1,3,4-tetramethylsi-
lole, is illustrative; A Laporterie, H. Iloughmane and J. Dubac, Tetrahedron
Lett., 1983, 3521.
¶ Existing models that account for the stereoselectivity of ketone and enone
deprotonations are not easily extrapolated to explain the outcome from 4Af.
For a review see; J.O. Williams and M. J. Kelly, in Comprehensive Organic
Functional Group Transformations, ed. A. R. Katritzky, O. Meth-Cohn and
C. W. Rees, Pergamon, Oxford, 1995, vol. 1, p. 843.
∑ Stereochemistry assigned by analogy with (E)- and (Z)-3-isobutenylidene-
thiophen-2(3H)-ones (ref. 13). Compound 8: d (CDCl3) 7.78 (1H, d, J 12.2,
NCHCHCMe2).
Support for the intermediacy of 4A was provided by the
behaviour of 3g, which gave the yellow (Z)-dienone 8 (mp
118–120 °C, 50%),∑ via isomerisation of 4Ag, as the only
identifiable product. Attempts to convert 8 into 5g by further
reaction with Me2NCOCl–pyridine were unsuccessful. Forma-
tion of the least substituted alkene is, apparently, disfavoured.
The carbamates 5 possess a contiguous triene system and
have the potential to cyclise with extrusion of Me2NCO2H to
give dibenzothiophenes. After much experimentation, it was
found that when 5a–f were heated in triethylene glycol (bp
285 °C) for 6 h formation of a new, non-polar compound was
complete (TLC). Aqueous work-up followed by flash chroma-
tography gave the novel fused systems 6a–e (30–42%). The
preparation of 6f (28%) represents an improved route to this
compound.14 Thermal isomerisation of the trans alkene moiety
in 5 precedes disrotatory ring closure and a concomitant Ei
reaction generates 6.
The dianion of 1 and 3-oxotetrahydrothiophene gave,
ultimately, 9 and 10 (38 and 25% from the pyranol), which were
1 R. K. Russell and J. B. Press, in Comprehensive Heterocyclic Chemistry
II, ed. A. R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon,
Oxford, 1996, vol. 2, p. 679.
NMe2
NMe2
O
O
2 J. Larsen and K. Bechgaard, Acta Chem. Scand., 1996, 50, 71, 77.
3 C. Bianchini and A. Meli, Synlett, 1997, 643.
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O
O
S
S
S
S
9
10
S
S
6 S. J. Collier and R. C. Storr, Prog. Heterocycl. Chem., 1998, 10, 25.
7 K. Buggle, Ú. N. Ghógaín, M. Nangle and P. MacManus, J. Chem. Soc.,
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S
S
S
11
12
13
8 Y. Tominaga and R. N. Castle, J. Heterocycl. Chem., 1996, 33, 523 and
references cited therein.
readily separated by flash chromatography. Thermal cyclisation
provided the tetracycles 11 (mp 84–85.5 °C, 44%) and 12 (mp
79–80.5 °C, 35%) respectively. In like manner the pentacycle
13 (mp 108–109 °C, 28%) was obtained via 2-tetralone.
Although the yields are modest this method offers a facile
entry to polycyclic thiophenes which is complementary to the
current protocols. Existing procedures would not permit ready
access to tetracycles 6a–e nor to the isobenzothiophene 12.
Applications to the synthesis of more complex polycycles will
be forthcoming.
9 J. C. Jutz, Top. Curr. Chem., 1979, 73, 125; C. Jutz, R.-M. Wagner and
H.-G. Löbering, Angew. Chem., Int. Ed. Engl.,1974, 13, 737.
10 L. S. Liebeskind and J. Wang, J. Org. Chem., 1993, 58, 3550.
11 S. Smiles and E. W. McClelland, J. Chem. Soc., 1921, 119, 1810.
12 For a review see, H. McNab, in Comprehensive Organic Functional
Group Transformations, ed. A. R. Katritzky, O. Meth-Cohn and C. W.
Rees, Pergamon, Oxford, 1995, vol. 1, p. 771.
13 I. J. Turchi, J. B. Press, J. J. McNally, M. P. Bonner and K. L. Sorgi,
J. Org. Chem., 1993, 58, 4629.
14 M. L. Tedjamulia, Y. Tominaga R. N. Castle and M. L. Lee,
J. Heterocycl. Chem., 1983, 20, 1485.
We thank the EPSRC for provision of the mass spectrometry
service at the University of Wales, Swansea, and James
Robinson Ltd. for financial support to J.-L. T.
Communication 9/00730J
542
Chem. Commun., 1999, 541–542