[A005]
Cycloaddition of Thiophene S-oxides to Allenes and to Benzyne
Hideki Fujii,a
Daisuke Ohira,a Shuntaro Matakab and Thies Thiemannb*
aInterdisciplinary Graduate School of
Engineering Sciences and bInstitute of Advanced Material Study,
Kyushu University, 6-1, Kasuga-koh-en, Kasuga-shi, Fukuoka 816-8580, Japan.
E-mail: [email protected]
Introduction
Until
recently, thiophene S-oxides[1] have been quite elusive molecules.
Nevertheless, two main routes towards the synthesis of these compounds have
been established: a.) by oxidation of the corresponding thiophenes;[2]
b.) by the reaction of alkynes with zirconocene dichloride via the
corresponding substituted zirconacyclopentadienes, which with sulfur dioxide or
thionylchloride are transformed to the thiophene S-oxides [3] Substituted thiophene S-oxides may be viewed as reactive dienes and can be utilized as
the 4p-component in Diels-Alder type
reactions.[4] Thus, thiophene S-oxides
have been reacted with both alkenes to give 7-thiabicyclo[2.2.1]heptene S-oxides and with alkynes to give
substituted arenes. In these reactions it could be seen that both electronic
factors as well as steric factors play an important role in the outcome of the
reaction, epecially in whether the cycloaddition proceeds at all. Limiting
factors peculiar to thiophene S-oxides
are the ease of self dimerisation, shared with some other cyclic dienes, and
the deoygenation reaction of thiophene S-oxides,
especially in the presence of easily oxidizable dienophiles such as
methylenecyclopropanes. In this contribution, the authors have focussed on the
cycloaddition behaviour of thiophene S-oxides
to allenes and to benzyne.
Results and Discussion
Two
differently substituted thiophene S-oxides,
tetraphenylthiophene S-oxide (3) and tetramethylthiophene S-oxide (7), have been used in this study. 3 is a sterically congested compound with substituents of slightly
withdrawing nature. 7 is sterically
a less exacting molecule with electron donating substituents. 3 and 7 were reacted with allenes 10,
12, and 15, where these differ in the electronic and steric properties of
their substituents.
3 was prepared by the reaction of diphenylethyne (tolane) (1) with zirconocene dichloride[3],
while 7 was obtained from the
oxidation of tetramethylthiophene (6)
with m-CPBA in the presence of BF3.Et2O
as a Lewis acid catalyst.[2b,4a] (Scheme 1)
Allenes 10, 12, and 15 were prepared
by known methods.[5] Phenylallene [phenylpropadiene] (10) was synthesized in a two step
procedure via Skattebøl rearrangement of 1,1-dibromo-2-phenylcyclopropane (9) (MeLi, ether).[5a] 9 itself was prepared by dibromocarbene
addition to styrene (8), where the
reaction was run as a two-phase reaction under PTC-conditions (bromoform,
triethylbenzylammonium bromide, 50% aq. NaOH, styrene)[5b] Allenes 12a/12b were prepared by Wittig olefination of acyl chlorides 11. Octyloxyallene (15) was obtained in a two step
procedure from propargylic bromide by etherification with n-octanol (13) and
subsequent base induced alkyne-allene isomerisation in 14 (all Scheme 2).
Reactions
of thiophene S-oxides such as 16 with alkylidenecyclopropanes such as
with 17 (Scheme 3) had already been
carried out by the authors[4c] and cycloadducts had been obtained as
a single diastereoisomer in relatively good yield. Due to the oxidazibility of
the strained olefin, some thiophene S-oxide
was lost at the time due to deoxygenation. Taking the reaction one step
further, from ethyl acrylate via ethyl cyclopropylideneacetate, the authors
decided to look at the reactivity of the thiophene S-oxides towards allenes,
such as towards ethyl propadienoate. When comparing 12a and 17, it is
evident that the olefinic moiety in 12a
possesses less strain energy than that of 17,
nevertheless, the mono-substituted 12a
is sterically less exacting.
On the
other hand, cycloaddition of 12a to
thiophene S-oxides would give bridged
thiabicyclo[2.2.1]heptene S-oxides
such as 20, which additionally
possess an exo-methylene function.
Whereas the cycloaddition of methylenecyclopropanes such as 17 results in the formation of a
spirocyclopropane unit, which is quite stable under the conditions of its
formation and suppresses the extrusion of the SO-bridge and the concurrent
aromatisation of the molecules, as partly seen in the reaction of thiophene S-oxides with 1,2-disubstituted alkenes,
some aromatisation was expected to occur in the case of the reaction of 7 with ethyl propandienoate (12a) via isomerisation of the exo-olefin to an endo-olefin, which, as a thiabicyclo[2.2.1]heptadiene S-oxide, would spontaneously extrude the
SO-bridge and would form a functionalized arene. Surprisingly, when 7 was heated with 12a in chloroform at 60C for 12h only the cycloadduct 20 could be observed. The yield is very
close to that found for the same reaction of a thiophene S-oxide with ethyl cyclopropylidene acetate (17).[4c] Pertinent 13C NMR data[7]
of the compound 20 (Figure 1) are
the chemical shifts, dC = 69/75 ppm, of the two quaternary carbons,
which are indicative for the bridge head carbons of the sulfoxy bridge; also
informative are the absorptions of the carbons of the exo-methylene functionality with the methylene carbon at dC = 111 ppm and the quaternary carbon at dC = 147 ppm. 20 is formed as one isomer only with endo-stereochemistry and the lone pair of the electron pair on
sulfur pointing towards the newly formed double bond within the carbocyclic
framework.[8] Interestingly, in the reaction of the
tetraphenylthiophene S-oxide (3) and
allene 12a only the aromatized
products 21a and 21b could be isolated. This seems to
indicate that the steric factor is important for the non-selectivity of the
attack, ie. both olefinic moities of
the allene react equally; while one is favored electronically, the other is
favored sterically. Also the aromatisation of the primary cycloadduct decreases
some steric congestion.
As the
appended phenyl substituents are not in full conjugation to the aromatic core,
due to out of plane rotation, stabilisation through conjugation with the phenyl
substituents may not necessarily play an important role in the release of the
sulfoxy bridge, when one compares the situation with that of 20.
Reaction of
tetramethylthiophene S-oxide (7) and phenylallene (10) again leads to two products, 19a and 19b, stemming from comparative reactivity of the two olefinic
moities of the allene. Here, the phenyl substituted olefinic moiety is not as
favored electronically as in 12a and
thus a greater reactivity balance is found between the sterically less
exacting, non-substituted olefinic moiety and the phenyl substituted moiety. No
aromatized products have been isolated from this reaction. With the donor
substituent allene 15,
tetramethylthiophene S-oxide (7) and tetraphenylthiophene S-oxide (3) show comparative reactivity. Both react at the non-substituted
side. In both cases similar yields are found and similar amounts of aromatized
product are observed. The initially formed enol ethers are hydrolysed during
work up to the corresponding aldehydes 22a/b
and 23a/b.
In their
study of the reactivity of substituted thiophene S-oxides as diene components in Diels-Alder type reactions, the
authors have also recently employed benzyne (29) as the ene-component. While there are a number of methods[8]
towards the preparation of benzyne, in this case it was important to use a
procedure under mild, non-reductive and not too basic conditions. This is
offered by the method of T. Kitamura et al.[9] from o-(trimethylsilyl)phenyl(phenyl)iodonium
triflate (25), which can be prepared
from o-dichlorobenzene in two steps.
When tetrabutylammonium fluoride is added to 25[10] in THF, benzyne is formed in situ. It can be reacted with thiophene S-oxides. When 1:1 mixture of thiophene S-oxide 27[11]
and 25 (ie., 29) were reacted
accordingly, the cycloadduct 28 was obtained
in 55% yield (Scheme 5). The reaction of 5 eq. of tetraphenylthiophene S-oxide with 25 at rt gave the respective cycloadduct in quantitative yield, as
calculated on 25. A very good
indication that from their chemical behavior, dibenzothiophene S-oxides, such as 24, should not be viewed as annelated thiophene S-oxides but rather as sulfoxy-bridged
diaryls can be obtained from the fact that dibenzothiophene S-oxide 24 is totally unreactive towards benzyne (29) under the conditions described above (Scheme 5).
In
conclusion, thiophene S-oxides react
as diene component with allenes in a [4+2]-cycloaddition reaction.
Tetra-substituted thiophene S-oxides
are very sensitive towards steric prerequisites. Thiophene S-oxides also react with benzyne, formed in situ.
Experimental
Example
1,4-Dimethyl-2,3-bis(p-methoxyphenyl)naphthalene (28) - Reaction of a Thiophene S-oxide with Benzyne, formed in situ:
At 0C and
within 10 min, a solution of n-tetrabutylammonium
fluoride (TBAF) (78 mg, 0.3 mmol) in THF (0.5 mL) was slowly added to a mixture
of 27 (68 mg, 0.2 mmol) and 25 (100 mg, 0.2 mmol) in CH2Cl2
(1 mL). The resulting solution was stirred for 1h at rt. Then, water (5 mL) was
added and the reaction mixture was extracted with CH2Cl2
(3 X 5 mL). The organic phase was dried over anhydrous MgSO4 and
concentrated in vacuo. The residue
was subjected to column chromatography on silica gel to give 28 (40 mg, 55%) as colorless needles:
IR (KBr) n 3064, 2992, 2920, 1610, 1513, 1286,
1035, 759 cm-1; 1H NMR (270 MHz, CDCl3) d 2.43 (s, 6H, 2 CH3), 3.75 (s, 6H, 2
OCH3), 6.70 (d, 2H, 3J
8.7 Hz), 6.87 (d, 2H, 3J
8.7 Hz), 7.56 (m, 2H), 8.12 (m, 2H); 13C NMR (67.8 MHz, CDCl3,
DEPT 90, DEPT 135)* d 16.87 (2C, 2 CH3), 55.07
(2C, 2 OCH3), 125.01 (2C, CH), 125.62 (2C, CH), 129.77 (2C, Cquat),
131.37 (4C, CH), 132.02 (2C, Cquat), 134.30 (2C, Cquat),
139.44 (2C, Cquat), 157.52 (2C, Cquat); MS (70 eV) m/z (%) 368 (M+, 100). HRMS
Found: 368.1779. Calcd. for C26H24O2:
368.1776. (M+)
References
and Footnotes:
[1]
For a
recent review on thiophene S-oxides,
see: T. Thiemann, K. Gopal Dongol, J.
Chem. Res. (S) 2002, 303.
[2]
[2a]P. Pouzet, I. Erdelmeier, D.
Ginderow, J.-P. Mornon, P. Dansette, D. Mansuy, J. Chem. Soc., Chem. Commun.
1995, 473; [2b]Y. Q. Li,
M. Matsuda, T. Thiemann, T. Sawada, S. Mataka, M. Tashiro, Synlett 1996, 461; [2c]J.
Nakayama, T. Yu, Y. Sugihara, A. Ishii, Chem.
Lett. 1997, 499; [2d]N.
Furukawa, S. Zhang, S. Sato, M. Higaki, Heterocycles
1997, 44, 61.
[3]
[3a]P. J. Fagan, W. A. Nugent, J. Am. Chem. Soc. 1988, 110, 2310; [3b]F.
Meier-Brocks, E. Weiss, J. Organomet.
Chem. 1993, 453, 33; [3c]P. J. Fagan, W. A. Nugent, J. C. Calabrese,
J. Am. Chem. Soc. 1994, 116, 1880; [3d]B. T. Jiang, T. D. Tilley, J. Am. Chem. Soc. 1999, 121, 9744; [3e]M.
C. Suh, B. T. Jiang, Angew. Chem. 2000, 112, 2992; Angew. Chem. Int.
Ed. Engl. 2000, 39, 2870.
[4]
[4a]Y. Q. Li, T. Thiemann, T. Sawada, S.
Mataka, M. Tashiro, J. Org. Chem. 1997, 62, 7926; [4b]Y. Q. Li, T. Thiemann, K. Mimura, T.
Sawada, S. Mataka, M. Tashiro, Eur. J.
Org. Chem. 1998, 1841; [4c]T.
Thiemann, D. Ohira, Y. Q. Li, T. Sawada, S. Mataka, K. Rauch, M. Noltemeyer, A.
de Meijere, J. Chem. Soc., Perkin Trans. 1 2000, 2968; [4d]N. Furukawa, S.-Z. Zhang, E. Horn, O.
Takahashi, S. Sato, M. Yokoyama, K. Yamaguchi, Heterocycles 1998, 47, 793.
[5]
[5a]T. R. Chen, M. R. Anderson, S.
Grossman, D. G. Peters, J. Org. Chem.
1987, 52, 1231; [5b]V. D. Novokreshchennykh, S. S. Mochalov,
Yu. S. Shabarov, Zh. Org. Khim. 1979, 15, 485 (Russ.); J. Org.
Chem. USSR 1979, 430 (Engl.) and
ref. cited; [5c]R. W. Lang, H.-J. Hansen, Helv. Chim. Acta 1980, 63, 438; [5d]A. Hausherr, B.
Orschel, S. Scherer, H.-U. Reissig, Synthesis
2001, 1377 and ref. cited.
[6]
R.
Gaertner, R. G. Tonkyn, J. Am. Chem. Soc.
1951, 73, 5872.
[7]
Typical
spectral data: (19a): IR (KBr) n 3056, 3030, 2970, 2924, 1642, 1598, 1492,
1449, 1376, 1090, 1063, 913, 768, 705 cm-1; 1H NMR (270
MHz, CDCl3) d 1.30 (s, 3H, CH3), 1.37
(s, 3H, CH3), 1.59 (s, 3H, CH3), 1.81 (s, 3H, CH3),
4.12 (m, 1H)**, 5.05 (d, 1H, 2J
2.3 Hz), 5.18 (d, 1H, 2J,
2.3 Hz), 6.98 - 7.02 (m, 2H, phenyl-H), 7.23 - 7.27 (m, 3H, phenyl-H); 13C
NMR (67.8 MHz, DEPT 90, DEPT 135) d 10.57 (+, CH3), 10.98
(+, CH3), 12.29 (+, CH3), 12.64 (+, CH3),
53.53 (+, CH), 70.91 (Cquat), 75.54 (Cquat), 111.57 (-),
127.06 (+, CH), 128.12 (+, CH), 129.42 (+, CH), 130.69 (Cquat),
131.68 (Cquat), 139.23 (Cquat), 152.24 (Cquat);
(19b): 1H NMR (270 MHz,
CDCl3) d 1.52 (s, 3H, CH3), 1.63
(s, 3H, CH3), 1.70 (s, 3H, CH3), 1.74 (s, 3H, CH3),
2.61 (dd, 1H, 2J 16.2 Hz, 4J 2.0 Hz), 3.09 (dd, 1H, 2J 16.2 Hz, 4J 1.8 Hz), 6.31 (dd, 4J 2.0 Hz, 4J 1.8 Hz), 7.20 - 7.42 (m, 5H); 13C
NMR (67.8 MHz, CDCl3, DEPT 90, DEPT 135) d 11.00 (+,
CH3), 11.50 (+, CH3), 13.64 (+, CH3), 15.24
(+, CH3), 37.38 (-), 67.64 (Cquat), 77.70 (Cquat),
124.60 (+, CH), 126.92 (+, CH), 128.24 (+, CH), 129.45 (+, CH), 131.50 (Cquat),
132.60 (Cquat), 137.34 (Cquat), 141.04 (Cquat).
*The assignment of the C-signals has been aided by DEPT experiments (DEPT =
Distortionless Enhancement of Polarisation Transfer), where (+) denotes primary
and tertiary carbons, (-) secondary carbons and (Cquat) quaternary
carbons.**1H-1H COSY experiment shows that in 19a there is a long-range coupling
between the methylidene proton on the carbocycle adjacent to the phenyl
substituent and both exo-methylene
protons; from the 270 MHz 1H NMR spectrum it has not been possible
to obtain the coupling constants for either of the couplings.
[8]
For
preparation and use of benzyne as dienophile, see: [8a]R. W.
Hoffmann, 'Dehydrobenzenes and Cycloalkynes',
Academic Press, New York 1967, pp. 200. For further use of benzyne prepared in
situ, see: [8b]M. R. Bryce, J. M. Vernon Adv. Heterocycl. Chem. 1981,
28, 183.
[9]
T.
Kitamura, M. Yamane, K. Inoue, M. Todaka, N. Fukatsu, Z. Meng, Y. Fujiwara, J. Am. Chem. Soc. 1999, 121, 11674.
[10]
The
authors thank Prof. T. Kitamura, Saga University (formerly Kyushu University,
Japan) for a generous donation of (phenyl)[o-trimethylsilyl]phenyl]iodonium
triflate.
[11] The thiophene S-oxide was prepared from the corresponding thiophene by oxidation with m-CPBA in presence of BF3.Et2O, see ref. 4c. Likewise dibenzothiophene S-oxide has been prepared by oxidation with m-CPBA, see also: T. Thiemann, K. Arima, K. Kumazoe, S. Mataka, Rep. Inst. Adv. Mat. Study Kyushu Univ. 2000, 14(2), 139; Chem. Abstr. 2001, 134, 326 318a.