Michael additions of oxygen and sulfur nucleophiles to 3,4-Di-t-butyl-1-[(p-tolyl)sulfonylimino]-1,1-dihydrothiophene. A comparison study with 3,4-Di-t-butylthiophene 1-oxide and 1,1-dioxide

Article abstract of DOI:10.1246/cl.2000.744

The reactions of 3,4-di-t-butyl-1-[(p-tolyl)sulfonylimino]-1,1-dihydrothiophene with RONa and RSNa furnished 2-alkoxy-and 2-alkylthio-substituted thiophenes, respectively, through Michael adduct formation. The reaction of 3,4-di-t-butylthiophene 1-oxide with RSNa gave 1,6-Michael adducts, whereas the corresponding reaction of 3,4-di-t-butylthiophene 1,1-dioxide produced a mixture of 1,4-and 1,6-adducts.

Full text of DOI:10.1246/cl.2000.744

744
Chemistry Letters 2000
Michael Additions of Oxygen and Sulfur Nucleophiles to
3,4-Di-t-butyl-1-[(p-tolyl)sulfonylimino]-1,1-dihydrothiophene.
A Comparison Study with 3,4-Di-t-butylthiophene 1-Oxide and 1,1-Dioxide
Takashi Otani, Yoshiaki Sugihara, Akihiko Ishii, and Juzo Nakayama*
Department of Chemistry, Faculty of Science, Saitama University, Urawa, Saitama 338-8570
(Received April 14, 2000; CL-000355)
The reactions of 3,4-di-t-butyl-1-[(p-tolyl)sulfonylimino]-
thiophenes (5a) (74%) and (5b) (49%), respectively. In the case
of the latter nucleophile, the configurationally pure 1,3-diene (7),
containing two phenylthio groups, was also isolated in 20%
yield.9,10 Assignment of the stereochemistry of the dienes 6a and
7 is based on the mechanistic grounds as discussed later.
Although it is known that alkaline treatment of sulfilimines
produces the corresponding sulfoxides,11 such hydrolysis of 2,
which leads to the 1-oxide 8, was never observed throughout this
study.
1,1-dihydrothiophene with RONa and RSNa furnished 2-
alkoxy- and 2-alkylthio-substituted thiophenes, respectively,
through Michael adduct formation. The reaction of 3,4-di-t-
butylthiophene 1-oxide with RSNa gave 1,6-Michael adducts,
whereas the corresponding reaction of 3,4-di-t-butylthiophene
1,1-dioxide produced a mixture of 1,4- and 1,6-adducts.
The chemistry of thiophene 1-oxides is a matter of recent
keen interest,1 whereas that of thiophene 1,1-dioxides has been
documented in full detail.2 On the other hand, the chemistry of
1-imino and 1,1-diimino derivatives of thiophenes has been
scarcely studied. Thus, the 1-imino derivatives of tetrachloro-
thiophene had been the sole example of monocyclic thiophene
derivatives,3 until, quite recently, we have reported the prepara-
tion of 3,4-di-t-butyl-1-[(p-tolyl)sulfonylimino]-1,1-dihydrothio-
phene (2) and 3,4-di-t-butyl-1,1-bis[(p-tolyl)sulfonylimino]-1,1-
dihydrothiophene (3) by reaction of sterically congested 3,4-di-t-
butylthiophene (1) with N-(p-tolylsulfonylimino)phenyliodinane
(TsN=IPh).4 As the extension of this study, we have examined
detosylation of 2 to obtain the corresponding parent 1-imino
derivative. Interestingly, however, the attempted alkaline
hydrolysis of 2 in refluxing aqueous MeOH5 provided 3,4-di-t-
butyl-2-methoxythiophene (4a) as the major product, which
corresponds formally to the Pummerer reaction product.
Attempted detosylation of 2 by a conventional method, treat-
ment with concentrated H2SO4,6 produced a complex mixture
containing 1 and some other products. The above unexpected
results, which have never been observed in the chemistry of
thiophene 1-oxides and thiophene 1,1-dioxides, have led us to a
comparison study of nucleophilic reactivities of 2, 3,4-di-t-
butylthiophene 1-oxide (8)7 and 1,1-dioxide (9).8
Next, reactions of the 1-oxide 8 and 1,1-dioxide 9 with
nucleophiles were investigated for comparison. Either 8 or 9
failed to react with MeONa; both 8 and 9 were recovered quan-
titatively when heated with MeONa in refluxing MeOH for 48
h. Meanwhile, sulfur nucleophiles, MeSNa and PhSNa, reacted
with 8 in MeOH at room temperature to give the 1,6-Michael
adducts (10a) (90%) and (10b) (79%), respectively.9,12 It is
noteworthy that these reactions provides a facile synthesis of
cyclic alkenes 10 in which two bulky t-butyl groups are placed
in cis-orientation. When the reaction of 8 with MeSNa was car-
ried out under the forcing conditions (reflux, MeOH, 72 h), 5a
was formed at the sacrifice of 10a though in a low yield (11%),
thus suggesting that 1,6-adducts are the probable intermediates
for the formation of 4 and 5 from 2.
Finally, the reaction of 9 with MeSNa produced a mixture
of 1,6- and 1,4-adducts (11 and 12) in the ratio 56:44 in 94%
combined yield.9,12,13
Thus, the reaction of 2 with NaOH in refluxing aqueous
MeOH for 48 h gave 4a9,10 (75%) and p-toluenesulfonamide
(TsNH2) (79%), whereas 2 was inert to heating with NaOH in
aqueous dioxane at 80 °C for 24 h. Heating 2 with EtONa in
EtOH at 70 °C for 2 h also gave the 2-ethoxythiophene (4b)
(68%) and TsNH2 (69%), in addition to the further unexpected
product, configurationally pure 1,3-diene (6a), in 17% yield.9,10
Sulfur nucleophiles, MeSNa and PhSNa, reacted with 2
much more easily at room temperature in MeOH for 48 h to give
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
745
and E. L. Clennan, Tetrahedron Lett., 31, 4473 (1990).
T. Yoshimura, T. Omata, N. Furukawa, and S. Oae, J. Org.
Chem., 41, 1728 (1976).
J. Nakayama, T. Yu, Y. Sugihara, and A. Ishii, Chem. Lett., 1997,
499.
Although the reactivities of N-p-tolylsulfonylsulfilimines
toward nucleophiles have been examined extensively,11,14 the
aforementioned reactions on 2 are unprecedented. Reportedly,
the alkaline hydrolysis of cyclic N-p-tolylsulfonylsulfilimines
in MeOH gave Pummerer reaction products, α-methoxy-substi-
tuted sulfides, as main products,14a but the mechanism proposed
therein14a–b would not be true of the present case. Thus, the
reaction would be best explained as follows. The Michael addi-
tion of Nu– to the less hindered 2-position of 2 produces 2,5-
dihydrothiophenes (13) initially, which is followed by hydrogen
migration that leads to ylide intermediates (14). The Stevens-
like [1,2]-rearrangement of 14 then affords 2,5-dihydrothio-
phenes (15). Finally, base-catalyzed elimination of TsNH2
from 15 results in the formation of 2-substituted thiophenes 4
and 5. Meanwhile, the ring-opening of ylides 14 would provide
dienes 6. This type of ring-opening was reported on a series of
the sulfur ylides (16);15 the ring-opening process can be pre-
sumed as an electrocyclic process of 6π-electron system, which
takes place in a concerted disrotatory manner.16 Finally, the sub-
stitution reaction of 6b by excessive PhSNa explains the forma-
tion of 7. In addition, the formation of 6 (7) provides supporting
evidences for the intermediacy of the Michael adducts 13.
6
7
8
9
J. Nakayama, R. Hasemi, K. Yoshimura, Y. Sugihara, and S.
Yamaoka, J. Org. Chem., 63, 4912 (1998).
Satisfactory elemental analyses were obtained for all new com-
pounds.
10 4a: colorless crystals; mp 50–51 °C, 1H NMR (400 MHz, CDCl3)
δ = 1.43 (s, 9H), 1.50 (s, 9H), 3.86 (s, 3H), 6.46 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ = 33.0, 33.3, 35.4, 35.7, 61.0, 106.8,
1
129.6, 149.3, 162.1. 4b: colorless crystals; mp 46 °C; H NMR
(400 MHz, CDCl3) δ = 1.42 (t, J = 7.1 Hz, 3H), 1.43 (s, 9H), 1.51
(s, 9H), 4.05 (q, J = 7.1 Hz, 2H), 6.43 (s, 1H); 13C NMR (100
MHz, CDCl3) δ = 15.1, 33.1, 33.3, 35.3, 35.6, 70.0, 106.0, 129.5,
149.2, 161.0. 5a: colorless crystals; mp 29–30 °C; 1H NMR (400
MHz, CDCl3) δ = 1.46 (s, 9H), 1.66 (s, 9H), 2.49 (s, 3H), 7.13 (s,
1H); 13C NMR (100 MHz, CDCl3) δ = 23.3, 33.8, 33.9, 35.7,
36.8, 122.5, 133.3, 150.3, 152.0. 5b: colorless crystals; mp 58–59
1
°C; H NMR (400 MHz, CDCl3) δ = 1.51 (s, 9H), 1.64 (s, 9H),
7.02–7.05 (m, 2H), 7.08–7.12 (m, 1H), 7.21–7.25 (m, 2H) 7.33
(s, 1H); 13C NMR (100 MHz, CDCl3) δ = 33.9, 34.0, 36.0, 37.2,
125.1, 125.9, 126.5, 128.8, 140.8, 152.3, 154.8. 6a: colorless
crystals; mp 88–89 °C; 1H NMR (400 MHz, CDCl3) δ = 0.97 (s,
9H), 1.12 (s, 9H), 1.21 (t, J = 7.0 Hz, 3H), 2.43 (s, 3H),
3.65–3.75 (m, 2H, OCH2), 5.70 (bs, 1H, NH), 5.75 (s, 1H), 6.00
(s, 1H), 7.31 (d, J = 8.2 Hz, 2H), 7.82 (d, J = 8.2 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ = 15.4 (CH3), 21.5 (CH3), 30.9
(CH3), 32.3 (CH3), 33.0 (C), 36.3 (C), 67.6 (CH2), 124.0 (C),
125.9 (CH), 128.0 (CH), 129.6 (CH), 136.5 (C), 144.0 (C), 144.2
1
(CH), 146.8 (C). 7: colorless crystals; mp 60–60.5 °C; H NMR
(400 MHz, CDCl3) δ = 1.23 (s, 9H), 1.24 (s, 9H), 6.25 (s, 1H),
6.37 (s, 1H), 7.17–7.35 (m, 8H), 7.51–7.54 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ = 31.6, 31.8, 37.0, 37.1, 124.2, 126.2,
126.9, 128.2, 128.8, 128.9, 128.9, 129.0, 137.3, 137.7, 149.3,
149.6.
11 J. Day and D. J. Cram, J. Am. Chem. Soc., 87, 4398 (1965); D. R.
Rayner, D. M. von Scritz, J. Day, and D. J. Cram, J. Am. Chem.
Soc., 90, 2721 (1968); D. J. Cram, J. Day, D. R. Rayner, D. M.
von Scritz, D. J. Duchamp, and D. C. Garwood, J. Am. Chem.
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1
12 10a: colorless crystals; mp 118–119 °C; H NMR (400 MHz,
CDCl3) δ = 1.31 (s, 9H), 1.41 (s, 9H), 2.25 (s, 3H), 3.50 (d, J =
17.4 Hz, 1H), 4.20 (d, J = 17.4 Hz, 1H), 4.71 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ = 16.7 (CH3), 31.5 (CH3), 32.4 (CH3), 34.0
(C), 35.3 (C), 61.4 (CH2), 79.5 (CH), 138.4, (C), 140.1 (C); IR
1
(KBr) 1038 cm–1. 10b: colorless crystals; mp 105–109 °C; H
NMR (400 MHz, CDCl3) δ = 1.34 (s, 9H), 1.48 (s, 9H), 3.50 (dd,
J = 1.1, 17.7 Hz, 1H), 4.21 (d, J = 17.7 Hz, 1H), 5.12 (s, 1H),
7.32–7.37 (m, 3H), 7.49–7.53 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ = 31.5, 32.6, 34.2, 35.5, 61.0, 80.1, 128.3, 129.4, 132.0,
133.2, 137.7, 141.7. 11: 1H NMR (400 MHz, CDCl3) δ = 1.28 (s,
9H), 1.40 (s, 9H), 2.33 (s, 3H), 3.63 (dd, J = 0.8, 16.4 Hz, 1H),
4.12 (d, J = 16.4 Hz, 1H), 4.43 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ = 15.1, 31.1, 32.4, 35.0, 36.4, 56.0, 71.4, 140.5, 142.1.
In conclusion, 2, 8, and 9 all serve as Michael acceptors
toward thiolates, whereas only 2 is reactive to alkoxides. In
addition, the Michael adducts of 2 undergo a Stevens-like [1.2]-
rearrangement to furnish the formal Pummerer reaction prod-
ucts.
1
12: H NMR (400 MHz, CDCl3) δ = 1.28 (s, 9H), 1.46 (s, 9H),
References and Notes
2.02 (s, 3H), 3.49 (d, J = 15.5 Hz, 1H), 3.96 (d, J = 15.5 Hz, 1H),
6.66 (s, 1H); 13C NMR (100 MHz, CDCl3) δ = 13.1, 28.9, 33.4,
37.9, 40.9, 61.2, 69.9, 133.0, 164.5.
1
For reviews, see, for example, J. Nakayama and Y. Sugihara,
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13 A less bulky nucleophile HOO– adds exclusively to the more hin-
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2
3
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16 R. B. Woodward and R. H. Hoffman, “The Conservation of
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4
5
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