non-Kekule´ biradicals 7a-d were intercepted as the 1:1 adducts 8-12 in good to excellent yields. The pyrolysis of sultines and sulfolenes with different concentrations of dienophiles revealed that either a preequilibrium between starting reagents and biradical species or Diels-Alder and retro-Diels-Alder reaction mechanisms may be involved; however, more work is necessary to establish the proposed mechanisms. Reaction of sultine 5b with nBuLi was found to undergo a nucleophilic ring-opening reaction to give sulfinyl alcohol 17 after H2O workup. When sultine 5a was heated in
benzene in a sealed tube in the presence of methanol, methanol-d4, or 2-mercaptoethanol, the
respective 1:1 trapping adducts 19-21 as well as the rearranged sulfolene 6a were isolated in similar amounts. The isolation of adducts 19-21 may be explained by the involvement of either biradical or ionic intermediates during the pyrolysis.
Introduction
The study of heterocyclic fused o-quinodimethane (o-QDM, 1) has received considerable current interest,1and
many methods have been developed for the generation of o-QDM; for example, azo compounds, sulfolenes,
ben-zocyclobutenes, and dihalides are popular precursors. Although azo compounds are popular for the generation of o-QDMs because of their clean thermal and photo-chemical reactions, they are notorious for their thermal instability in thieno- and pyrrolo-fused diazenes.2b,c On
the contrary, sulfolenes are so stable that harsh reaction conditions, such as flash vacuum pyrolysis or high-temperature pyrolysis, are usually required.1c,d,g
Benzo-cyclobutenes are also useful precursors, but they often come from other precursors;1h,itherefore, an extra step
in synthesis is usually required. Dihalides are useful in thermal reactions; however, they usually require the addition of other catalysts1a,e,ito enhance the reactivity.
We choose sultines3-5as precursors for o-QDM because
they are usually stable above room temperature and yet react thermally at milder conditions than sulfolenes.
Pioneering studies on benzosultine and derivatives as o-QDM precursors had been explored by Durst et. al in the last two decades,4but further development of other
sultines was hampered by their tedious synthesis. The successful application of Rongalite in the conversion of
(1) For reviews of o-quinodimethanes, benzocyclobutenes, and re-lated chemistry, see: (a) Segura, J. L.; Martı´n, N. Chem. Rev. 1999, 99, 3199. (b) Collier, S. J.; Storr, R. C. In Progress in Heterocyclic Chemistry; Gribble, G. W., Gilchrist, T. L., Eds.; Pergamon: New York, 1998; Vol. 10, pp 25-48. (c) Ando, K.; Kankake, M.; Suzuki, T.; Takayama, H. Tetrahedron 1995, 51, 129. (d) Chou, T.-S. Rev. Heteroatom Chem. 1993, 8, 65. (e) Martı´n, N.; Seoane, C.; Hanack, M. Org. Prep. Proced. Int. 1991, 23, 237. (f) Charlton, J. L.; Alauddin, M. M. Tetrahedron 1987, 43, 2873. (g) Funk, R. L.; Vollhardt, K. P. C. Chem. Soc. Rev. 1980, 9, 41. (h) Kametani, T. Pure Appl. Chem. 1979, 51, 747. (i) Oppolzer, W. Synthesis 1978, 793; Heterocycles 1980, 14, 1615.
(2) (a) Berson, J. A. Acc. Chem. Res. 1997, 30, 238. (b) In a study by Lu et al. the thiophene diazene was unstable below -10 °C: Lu, H. S. M.; Berson, J. A. J. Am. Chem. Soc. 1996, 118, 265. (c) The azo precursor was reported to be stable only below -20 °C by Bush et al.: Bush, L. C.; Heath, R. B.; Berson, J. A. J. Am. Chem. Soc. 1993, 115, 9830.
(3) (a) Wu, A.-T.; Liu, W.-D.; Chung, W.-S. J. Chin. Chem. Soc. 2002, 49, 77. (b) Liu, J.-H.; Wu, A.-T.; Huang, M.-H.; Wu, C.-W.; Chung, W.-S. J. Org. Chem. 2000, 65, 3395. (c) Chung, W.-W.-S.; Liu, J.-H. Chem. Commun. 1997, 205. (d) Chung, W.-S.; Lin, W.-J.; Liu, W.-D.; Chen, L.-G. J. Chem. Soc., Chem. Commun. 1995, 2537.
(4) For some earlier works on sultines, see: (a) King, J. F.; Rathore, R. Tetrahedron Lett. 1989, 30, 2763. (b) Durst, T.; Charlton, J. L.; Mount, D. B. Can. J. Chem. 1986, 64, 246. (c) Charlton, J. L.; Durst, T. Tetrahedron Lett. 1984, 25, 5287. (d) Jung, F.; Molin, M.; Van Den Elzen, R.; Durst, T. J. Am. Chem. Soc. 1974, 96, 935. (e) Connolly, T. J.; Durst, T. Tetrahedron Lett. 1997, 38, 1337. (f) Sharma, N. K.; De Reinach-Hirtzbach, F.; Durst, T. Can. J. Chem. 1976, 54, 3012. (g) Roversi, E.; Monnat, F.; Schenk, K.; Vogel, P.; Bran˜ a, P.; Sordo, J. A. Chem.sEur. J. 2000, 6, 1858 and earlier references therein. (h) Megevand, S.; Moore, J.; Schenk, K.; Vogel, P. Tetrahedron Lett. 2001, 42, 673.
(5) For a review of sultines, see: Dittmer, D. C.; Hoey, M. D. The Chemistry of Sulphinic Acids, Esters, and Their Derivatives; Wiley: Chichester, U.K., 1990; pp 239-273.
dihalides to sultines by Hoey and Dittmer5,6makes it a
convenient precursor for o-QDM. Although the applica-tion of sulfolenes and sultines as o-QDM precursors has been popular, important questions remain to be answered concerning their differences in reactivity and reaction mechanisms. In their pyrolysis studies of sulfolenes with alkenes, Takayama et al. reported1c,7that Diels-Alder
reaction occurred first on the aromatic moiety, followed by SO2extrusion, then a second Diels-Alder reaction to
give 1:2 cycloadducts, and finally a retro-Diels-Alder reaction to give the 1:1 fused adducts (vide infra).
We have been interested in the application of hetero-cyclic fused o-QDM in Diels-Alder reactions,3and in this
work R,R′-disubstituted thienosultines are synthesized to find out whether sultines react through the mechanism proposed by Takayama for sulfolenes or through a biradical mechanism similar to those of diazenes.2On one
hand, the bulky R,R′-disubstituents on thienosultines may have two functions: (1) they hinder the direct addition of dienophiles to R-positions of thiophene, and (2) the phenyl group(s) may stabilize the thus formed non-Kekule´ biradicals. Therefore, if the 1:1 fused adducts are still formed with the bulky substituents, the biradical mechanism may be involved. Furthermore, concentra-tion-dependent trapping studies on the pyrolysis of sulfolenes and sultines are carried out in the hope to differentiate their reaction mechanisms on the basis of whether their rate-determining steps are unimolecular or bimolecular reactions. We herein report our explora-tion of the scope of thienosultine derivatives and their thermal reaction with various dienophiles and nucleo-philes.
Results and Discussion
The syntheses of 2,5-disubstituted thienosultines 5a-d are shown in Schemes 1 and 2. 2,5-Dimethylthiophene (3a) and 2,5-dichlorothiophene (3b) are commercially
available. Butyllithium treatment of 2-phenylthiophene (2)8afollowed by methylation led to
2-methyl-5-phenyl-thiophene (3c) in 97% yield. 2,5-Diphenyl2-methyl-5-phenyl-thiophene (3d) was prepared by a known method using a palladium catalyst.8b 2,5-Disubstituted
3,4-bis(chloromethyl)-thiophenes 4a-d were prepared by chloromethylation of the corresponding 2,5-disubstituted thiophenes 3a-d adapted according to the procedures developed by Wyn-berg et al. in the synthesis of the corresponding sulfones 6.9a,bThe key step in the synthesis of sultines 5a-d is
the use of Rongalite (sodium formaldehyde sulfoxylate) with the corresponding dichlorides 4a-d. Unfortunately, the yields for the preparation of these sultines are relatively poor compared to that of ca. 70% for the preparation of benzosultine,5,6 and there is room for
further improvement of the thienosultine synthesis. The1H NMR spectra of sultines 5a-d deserve some
comments because they show two characteristic AB quartets of the 1,4-hydrogens near oxathiin-3-oxide func-tional groups. It has been reported that hydrogens on the carbon R to the oxygen of an oxathiin-3-oxide (sultine) have chemical shifts of 4.9-5.6 ppm, whereas hydrogens on the carbon R to the sulfinyl of an oxathiin-3-oxide have chemical shifts of 3.5-4.7 ppm.3-4,11bThe four
R-hydro-gens of sulfolenes 6a-d have chemical shifts in the range of 4.1-4.4 ppm and appear as singlets (except those for 6c, for which two singlets were observed) due to sym-metry and lack of a nearby chiral center. In the five thienosultines we have studied, the chemical shifts of hydrogens in sultines 5a-d fell into two regions, 3.6-4.4 and 4.9-5.5 ppm (see the Experimental Section), which are in good agreement with the above description. The magnitude of the geminal coupling constant of the hydrogens R to the oxygen, Jcd, is usually smaller than
that of hydrogens R to the sulfinyl group of a sultine (i.e., Jab). The former are in the range of 13.6-14.9 Hz,
whereas the latter are in the range of 15.3-16.0 Hz (see Table 1). The assignments of thienosultine 1H NMR
chemical shifts are based on previous assignments by Pirkle on benzosultines11band the known propensity of
(6) (a) Hoey, M. D.; Dittmer, D. C. J. Org. Chem. 1991, 56, 1947. (b) Jarvis, W. F.; Hoey, M. D.; Finocchio, A. L.; Dittmer, D. C. J. Org. Chem. 1988, 53, 5750.
(7) (a) Ando, K.; Aakadegawa, N.; Takayama, H. J. Chem. Soc., Chem. Commun. 1991, 1765. (b) Ando, K.; Kankake, M.; Suzuki, T.; Takayama, H. Synlett 1994, 741. (c) Konno, K.; Kawakami, Y.; Hayashi, T.; Takayama, H. J. Chem. Soc., Perkin Trans. 1 1994, 1371. (d) Chou, T.-S.; Tseng, H.-J. Tetrahedron Lett. 1995, 36, 7105. (e) Chou, S.-S. P.; Lee, C.-S.; Cheng, M.-C.; Tai, H.-P. J. Org. Chem. 1994, 59, 2010.
(8) (a) Rossi, R.; Carpita, A.; Ciafalo, M.; Lippolis, V. Tetrahedron 1991, 47, 8443. (b) Campaigne, E.; Foye, W. J. Org. Chem. 1952, 17, 1405.
(9) (a) Wynberg, H.; Zwanenburg, D. J. J. Org. Chem. 1964, 29, 1919. (b) Zwanenburg, D. J.; Wynberg, H. J. Org. Chem. 1969, 34, 333. (c) Winn, M.; Bordwell, F. G. J. Org. Chem. 1967, 32, 1610.
SCHEME1a
aReagents and conditions: (a) nBuLi, THF, 0 °C, 3 h; ZnCl 2, rt, 2 h; (b) PhBr, Pd(PPh3)4, THF, 55 °C, 24 h; (c) nBuLi, THF, 0 °C, 3 h; CH3I, 0 °C f rt, 24 h.
protons cis to a sulfinyl oxygen to be deshielded; there-fore, Hbis downfield shifted from Haand Hdis downfield
shifted from Hc.11d
Sealed tube reaction of sultines 5a-d in benzene alone gave the corresponding sulfolenes 6a-d in excellent yields (83-94%). The Diels-Alder reactions of sultines 5a-d and sulfolenes 6a-d with typical electron-poor dienophiles are presented in Scheme 3 and Table 2. For example, when heated in benzene (sealed tube, 180 °C, 24 h) in the presence of 3 equiv of N-phenylmaleimide, dimethyl fumarate, fumaronitrile, dimethyl acetylene-dicarboxylate, or diethyl fumarate, the sultines 5a-d all underwent extrusion of SO2, and the resulting
non-Kekule´ biradicals 7a-d were intercepted as the 1:1 fused adducts 8-12 in 37-91% yields (entries 1-3, 5-7, 9-12, and 14-17 of Table 2). In each case, small to substantial amounts of sulfolenes 6a-d were also formed depending on the power of the dienophiles; that is, stronger dieno-philes led to higher yields of fused adducts and less sulfolenes. It is important to note that sulfolenes 6a-d did not react with any of these dienophiles under the same reaction conditions (entries 4, 8, 13, and 18 of Table 2). The low reactivity of sulfolenes 6a-d is in sharp contrast with the high reactivity of sultines 5a-d but is
consistent with those reported by Takayama,1c,7a-cChou,7d,e
and Wynberg9 in their early attempts. Furthermore, it
is interesting to observe the great similarity of our results with sultines and those with diazenes reported by Berson et al.2,10 For example, in the trapping experiments of
thiophene biradical 7e (X ) Y ) H) derived from a diazene precursor,10the sole adducts formed (85-100%)
had the fused structure (such as 8) but not the bridged structure 13 (see Scheme 4).
The pyrolysis results of these sultines may be ex-plained by at least three possible reaction mechanisms. The most likely pathway is the formation of non-Kekule´ biradicals 7a-d, followed by the Diels-Alder reaction with a dienophile to form either bridged adducts 13 or fused adducts 8-12 (pathway A, Scheme 3). This mech-anism resembles those proposed for thieno- or furano-(10) (a) Haider, K. W.; Clites, J. A.; Berson, J. A. Tetrahedron Lett. 1991, 32, 5305. (b) Stone, K. J.; Greenberg, M. M.; Blackstock, S. C.; Berson, J. A. J. Am. Chem. Soc. 1989, 111, 3659. (c) Greenberg, M. M.; Blackstock, S. C.; Berson, J. A. Tetrahedron Lett. 1987, 28, 4263. (d) Reynolds, J. H.; Berson, J. A.; Kumashiro, K. K.; Duchamp, J. C.; Zilm, K. W.; Scaiano, J. C.; Berinstain, A. B.; Rubello, A.; Vogel, P. J. Am. Chem. Soc. 1993, 115, 8073. (e) Greenberg, M. M.; Blackstock, S. C.; Berson, J. A. J. Am. Chem. Soc. 1989, 111, 3671. (f) Cichra, D.; Platz, M. S.; Berson, J. A. J. Am. Chem. Soc. 1977, 99, 8507. aEstimated accuracy for coupling constants is ca. (0.2 Hz. All measurements were done in CDCl
diazenes.2,10Alternatively, sultines may undergo a
one-bond (carbon-oxygen one-bond) cleavage to form alkyl sulfinyl biradicals of the type 7′a-d. The biradicals 7′a-d may then undergo either an intramolecular rearrangement to form sulfolenes 6a-d or an intermolecular trapping by olefins to form after losing SO2 the 1:1 fused adducts
(pathway B, Scheme 3). The third possible reaction mechanism of thienosultines 5a-d is to undergo a Diels-Alder reaction on the aromatic moieties first followed by instantaneous SO2 elimination to give bridged adducts
13. Compounds 13 further react with another dienophile to give the 1:2 adducts 15, and finally a retro-Diels-Alder reaction of 15 would occur to form fused adducts 8-12 (Scheme 4). The latter mechanism was proposed by Takayama to explain results with furano- and pyrrolosul-folenes.1c,7
In the mechanisms involving biradical intermediates (pathways A and B in Scheme 3), the rate will be dependent only on the sultine concentration if the dieno-phile concentration is kept high and a steady-state approximation of the biradical concentration is satisfied. However, if the dienophile concentration is low, the rate of reaction will be dependent not only on the concentra-tion of sultines but also on the concentraconcentra-tion of dieno-philes.11eAlternatively, if a Diels-Alder reaction occurs
first on the aromatic part of sultine and it happens to be the rate-determining step, the reaction would be second order and first order with respect to both the sultine and the dienophile. In the latter mechanism, the higher the dienophile concentration the faster products are formed and the faster starting sultines (or sulfolenes) are consumed. Because thienosulfolenes 6a-d required a much higher temperature to react with dienophiles, we used furanosulfolene 163dinstead and thienosultine 5a
for concentration-dependent kinetic studies.
Concentration-dependent studies on the thermolysis of thienosultine 5a (150 °C, 5 h) and furanosulfolene 16 (120 °C, 2 h) are shown in Figure 1. In the thermolysis of 5a, the yield of sulfolene 6a gradually decreased from 23% to ca. 2% when the concentration of fumaronitrile in-(11) (a) Andersen, K. K.; Foley, J.; Perkins, R.; Gaffield, W.; Papanikalaou, N. J. Am. Chem. Soc. 1964, 86, 5637. (b) Pirkle, W. H.; Hoekstra, M. S. J. Am. Chem. Soc. 1976, 98, 1832. (c) Harpp, D. N.; Vines, S. M.; Montillier, J. P.; Chan, T. H. J. Org. Chem. 1976, 41, 3987. (d) Alternatively, one may envision that the lone pair electrons on sulfur of a sulfinyl group could act to shield a proton cis-vicinal to it. (e) For an excellent monograph on the kinetics of reactions involving intermediates, see: Wentrup, C. Reactive Molecules; Wiley: New York, 1984; Chapter 1.
SCHEME3
TABLE2. Sealed Tube Reactions of 2,5-Disubstituted Thienosultines 5a-d and Sulfolenes 6a-d with Various Dienophiles (3 equiv) in Benzenea
entry diene dienophile
products (yield, %) total yield, % 1 5a N-phenylmaleimide 6a (6) + 8a (91) 97 2 5a dimethyl fumarate 6a (49) + 9a (40) 89 3 5a fumaronitrile 6a (46) + 10a (43) 89 4 6a various dienophilesb no reaction 0 5 5b N-phenylmaleimide 6b (7) + 8b (65) 72 6 5b dimethyl fumarate 6b (4) + 9b (64) 68 7 5b fumaronitrile 6b (16) + 10b (77) 93 8 6b various dienophilesb no reaction 0 9 5c N-phenylmaleimide 6c (16) + 8c (76) 92 10 5c fumaronitrile 6c (13) + 10c (75) 88 11 5c dimethyl acetylenedicarboxylate 6c (47) + 11c (37) 84 12 5c diethyl fumarate 6c (23) + 12c (69) 92 13 6c various dienophilesb no reaction 0 14 5d N-phenylmaleimide 6d (6) + 8d (82) 88 15 5d dimethyl fumarate 6d (12) + 9d (79) 91 16 5d fumaronitrile 6d (21) + 10d (75) 96 17 5d diethyl fumarate 6d (30) + 12d (67) 97 18 6d various dienophilesb no reaction 0
aAll reactions were carried out in benzene solution in a sealed tube at 180 °C for 24 h.bAll the dienophiles used in the table were tested for sulfolenes 6a-d.
creased from 0 to 0.25 M (Figure 1a). Concurrently, the percentage yield of cycloadduct 10a increased when the concentration of fumaronitrile increased. The results may be rationalized easily if diradical intermediates are invoked; that is, a competitive trapping of biradicals 7 by SO2or dienophile determines the relative amount of
sulfolene 6a and cycloadduct 10a. A similar explanation may be applied in the Diels-Alder and retro-Diels-Alder reaction mechanism (Scheme 4), where a competitive trapping of reactive diene 13 by dienophile or SO2
determines the relative product ratios. The consumption rate of furanosulfolene 16 is shown to be concentration dependent on both the sulfolene and fumaronitrile (Fig-ure 1b). That is, higher dienophile (or sulfolene) concen-tration led to faster consumption of sulfolene and faster formation of cycloadducts. It would certainly be desirable to differentiate the above mechanisms; however, more accurate kinetic data are necessary for such an analysis.
Such an analysis would require direct spectroscopic measurement as has been elegantly demonstrated in the pyrolysis of a diazene.10f However, we lack a proper
thermostated optical cell for the in situ monitoring of high-temperature kinetics. Although laser flash spec-troscopy and matrix isolation would also provide valuable information about the transient species, they are related to photochemical and photophysical properties of these sultines and may not be related to the thermolysis results discussed here. Clearly more work is necessary to estab-lish these proposed mechanisms.
It has long been known that the reaction of an optically active reagent on sulfinate esters (sultines) will lead to sulfoxides of high optical purity, the so-called Andersen synthesis.11aThese reactions are stereospecific and
pro-ceed with inversion at sulfur.11bNucleophilic ring opening
of heterocyclic fused sultines, however, has rarely been reported. Some of the few reported reactions of sultines with Grignard reagents as well as organocopper-lithium reagents11cwere mainly with aliphatic sultines. Reaction
of sultine 5b with nBuLi gave the sulfinyl alcohol 17 after workup by H2O; however, it gave a deuterated sulfinyl
alcohol, 18, as the main product if worked up by D2O
(Scheme 5). Careful inspection of the1H NMR spectrum
of 18 revealed that deuterium appeared only on the R-sulfinyl carbon, and no sign of deuterium scrambling in other carbons was found. The isolation of 18 as the FIGURE1. Product distributions of the sealed tube reactions
of sultine 5a and sulfolene 16 with various concentrations of fumaronitrile: (a) 2,5-dimethylthienosultine 5a (16.5 mM in toluene), reacted at 150 °C for 5 h, where closed circles indicate the yield (%) of sulfolene 6a, open triangles indicate the yield (%) of cycloadduct, and open squares indicate the yield (%) of the recovered sultine; (b) furanosulfolene 16 (15.8 mM in benzene), reacted at 120 °C for 2 h, where open circles indicate the yield (%) of recovered sulfolene and open triangles indicate the yield (%) of cycloadduct formed. All the reactions were stopped far before completion.
major product indicated that neighboring alkoxide might have undergone a H abstraction from the R-carbon of the sulfinyl group, giving hydroxyl and sulfinyl anion groups. The sulfinyl anion group eventually abstracts either a H from H2O or a deuterium from D2O to form 18 as the
finally observed product. Although yields for the nucleo-philic attack of cyclic sulfinate esters (sultines) by nBuLi are low (33-47%), they are comparable to the yields reported (40-70%) for aliphatic sultines.11a-c
Sulfolenes are well-known to undergo alkylation readily at their R-sulfonyl position upon deprotonation with nBuLi followed by methyl iodide and ethyl, butyl, and benzyl bromides, respectively.7 By contrast, sultines
undergo a nucleophilic attack if treated with a strong base such as a Grignard reagent or nBuLi; therefore, the synthesis of R-derivatives of sultines will not be straight-forward. Reminiscences of the work done by Durst indicated that sulfinyl alcohols 17 and 18 (so-called δ-hydroxy sulfoxides)4d,fmay be useful intermediates in
the synthesis of sultines.
To learn more about sultine chemistry and to deter-mine the nature of the reactive intermediates, we further explored the reaction of sultine 5a with radical trapping reagents such as methanol, 1,4-cyclohexadiene, and 2-mercaptoethanol.12-14 In the presence of
2-mercapto-ethanol in a sealed tube reaction in benzene, sultine 5a underwent SO2 extrusion and gave a radical (or ionic)
trapping product, 19, as well as the rearranged sulfolene 6a in a ca. 2:3 ratio, with a total yield of 50%. Similar trapping of the reactive intermediates by methanol gave 20 and sulfolene 6a in a ca. 1:1 ratio. The abstractions of a hydrogen and a methoxy group in product 20 were confirmed by a methanol-d4trapping experiment, where
the disappearance of a methyl ether signal and a decrease of the 3-methyl signal from an integration of three to two protons were observed in1H NMR spectra of adduct 21.
Although the formation of adducts 19-21 may be ex-plained by a biradical trapping mechanism, alternatively, it may also be explained by ionic intermediates similar to those used by Myers in their trapping of R,3-dehydro-toluene.13,14 The trapping of the reactive intermediate,
resulting from the pyrolysis of sultine 5a, by 1,4-cyclo-hexadiene was found to be inefficient even though it has been frequently used in the trapping of biradicals. The results implied that the biradicals might have been formed; however, they were either retrapped by SO2
(7a-d) or underwent intramolecular rearrangement (through 7′a-d) to give only sulfolene 6a in 86% yield. Alterna-tively, the latter results may favor the nucleophilic displacement by methanol or mercaptoethanol on the O-carbon atom to yield a sulfinic acid, which after losing SO2gives the observed products.15
In conclusion, we have synthesized 2,5-disubstituted thienosultines 5a-d and studied their thermal reactions
with electron-poor alkenes, alkynes, radical trapping agents, and nucleophiles. When heated in the presence of electron-poor dienophiles, sultines 5a-d underwent elimination of SO2, and the resulting biradicals (7a-d
or 7′a-d, Scheme 3) were intercepted as the 1:1 adducts 8-12 in good to excellent yields. In each case, small to substantial amounts of sulfolenes 6a-d were also formed. When sultine 5a was heated in benzene in a sealed tube in the presence of methanol or 2-mercaptoethanol, the respective trapping adducts 19-21 as well as the rear-ranged sulfolene 6a were isolated. Reaction of sultine 5b with nBuLi was found to undergo a nucleophilic ring-opening reaction to give sulfoxide alcohol 17 after H2O
workup. Sulfoxide alcohols can be further transformed into other sultine derivatives.4d,f
Concentration-depend-ent trapping of sultines and sulfolenes through thermoly-sis revealed that different reaction mechanisms may be involved. We are in the process of studying the photo-chemistry and transient absorption spectroscopy of these and other heterocyclic fused sultines,3and the results will
be reported in due course.
Experimental Section
General Procedures. Melting points were determined on
a melting point apparatus and are uncorrected. 1H NMR
spectra were recorded at 300 MHz, 13C and DEPT NMR
spectra were recorded at 75.4 MHz, and the chemical shifts are reported in parts per million (δ) relative to that of CDCl3 (δ ) 7.25 ppm for proton, and δ ) 77.00 ppm for carbon) or tetramethylsilane as internal standard. Coupling constants are reported in hertz (Hz). High-resolution mass spectra were recorded on a spectrometer of the instrument center of either National Tsing-Hua University or National Chung-Hsin Uni-versity. C, H, and N combustion analyses were determined, and all analyzed compounds are within (0.4% of the theoreti-cal value unless otherwise indicated. Column chromatography was performed on silica gel of 70-230 or 230-400 mesh. The preparation of 2 followed a literature8a procedure. The syn-thesis of dihalides 4a and 4b followed a literature procedure.9b,c Data for 2-Phenylthiophene (2): 98% yield; white solid;
mp 31-32 °C (lit.8amp 36 °C);1H NMR (300 MHz, CDCl 3) δ 7.03-7.05 (1H, m), 7.23-7.37 (5H, m), 7.58-7.61 (2H, m);13C NMR (75.4 MHz, CDCl3) δ 123.03 (CH), 124.75 (CH), 125.90 (CH), 127.41 (CH), 127.96 (CH), 128.84 (CH), 134.35 (Cq), 144.38 (Cq). Synthesis of 2-Methyl-5-phenylthiophene (3c). To a solution of 2 (4.36 g, 27.26 mmol) in THF (60 mL) at 0 °C was slowly added n-butyllithium (2.5 M in hexane, 30 mmol) via syringe under nitrogen. After the solution was stirred for 3 h, methyl iodide (8.1 g, 54 mmol) in THF (4 mL) was added dropwise with vigorous stirring. The reaction mixture was gradually warmed to ambient temperature and stirred over-night. The solution was poured into 50 mL of ice-water, the two layers were separated, and the aqueous layer was
ex-tracted with ether (3 × 50 mL). The organic layers were
combined, dried over MgSO4, filtered, and concentrated. Flash column chromatography on silica gel (hexane) gave 4.6 g (26
mmol, 97%) of 3c as a white solid: mp 39-41 °C;1H NMR δ
2.47 (3H, s), 6.70-6.69 (1H, m), 7.07-7.08 (1H, m), 7.21-7.55
(5H, m);13C NMR δ 15.45 (CH
3), 122.85 (CH), 125.47 (CH), 126.16 (CH), 126.96 (CH), 128.78 (CH), 134.68 (Cq), 139.48 (Cq), 141.96 (Cq).
Synthesis of 2,5-Diphenylthiophene (3d). A hexane solution of n-butyllithium (34.3 mmol) was added via syringe to a stirred solution of 2-phenylthiophene (5.0 g, 31.2 mmol) in anhydride THF (50 mL) at 0 °C under nitrogen. The mixture was stirred at this temperature for 3 h, and then transferred via syringe to a stirred solution of zinc chloride (4.68 g, 34.3 mmol) in 20 mL of anhydride THF at room temperature. The
(12) For examples of radical trapping by thiols, see: (a) Ottenheijm, H. C. J. J. Org. Chem. 1981, 46, 5408. (b) Tome, A. C.; Cavaleiro, J. A. S.; Storr, R. C. Tetrahedron 1996, 52, 1723.
(13) For efficient trapping of biradical intermediates using 1,4-cyclohexadiene, see: (a) Myers, A. G.; Kuo, E. Y.; Finney, N. S. J. Am. Chem. Soc. 1989, 111, 8057. (b) Myers, A. G.; Dragovich, P. S.; Kuo, E. Y. J. Am. Chem. Soc. 1992, 114, 9369.
(14) Storr et al. reported12b a similar observation of conjugate
addition of thiol nucleophiles on the pyrimidin-4-ones generated from the corresponding sulfolene with SO2extrusion.
(15) We thank one of the reviewers for the suggestion of this mechanism.
127.50 (CH), 128.90 (CH), 134.27 (Cq), 143.58 (Cq); MS (EI)
m/z 237 (M++ 1, 58), 236 (M+, 100), 202 (8).
General Procedure for the Synthesis of 2,5-Disubsti-tuted 3,4-Bis(chloromethyl)thiophenes 4a-d.9cThe pro-cedure for 4c is given as an example. Compound 3c (5.0 g, 28.7 mmol) was dissolved in carbon disulfide (10 mL), and chloromethyl methyl ether (7.3 g, 86 mmol) was added. The solution was cooled to 0 °C. A solution of tin tetrachloride (11.3 g, 43.05 mmol) in 10 mL of carbon disulfide was added dropwise via an additional funnel under nitrogen. The mixture turned dark green upon addition. The reaction mixture was stirred at 0 °C for 1 h and then warmed to room temperature for 2 h. The heterogeneous dark green mixture was poured into ice-water (20 mL), and CH2Cl2(40 mL) was added. After the mixture was stirred for 10 min, the layers were separated and the organic layer was washed with water (20 mL) and dried over MgSO4. The solvent was distilled off in vacuo to yield 3.7 g (1.37 mmol, 48%) of 4c as a viscous green oil. Product 4c decomposed after chromatography on silica gel; therefore, crude product was used without further purification. The isolated yields based on starting materials 3a-c are as follows: 4a, 41%; 4b, 69%; 4c, 48%; 4d, 64%.
Data for 3,4-Bis(chloromethyl)-2,5-dimethylthiophene (4a): white solid; mp 59-61 °C;1H NMR δ 2.40 (6H, s), 4.60
(4H, s); 13C NMR δ 12.75 (CH
3), 37.23 (CH2), 131.95 (Cq), 135.91 (Cq). Anal. Calcd for C8H10Cl2S: C, 45.95; H, 4.82. Found: C, 46.00; H, 4.85.
Data for 2,5-Dichloro-3,4-bis(chloromethyl)thiophene (4b): white solid; mp 38-39 °C (lit.9bmp 41-42 °C);1H NMR
δ 4.63 (4H, s);13C NMR δ 35.66 (CH
2), 126.94 (Cq), 132.88 (Cq). Anal. Calcd for C6H4Cl4S: C, 28.83; H, 1.61. Found: C, 29.05; H, 1.62.
Data for 3,4-Bis(chloromethyl)-2-methyl-5-phenyl-thiophene (4c):2bviscous green oil;1H NMR δ 2.48 (3H, s), 4.63 (2H, s), 4.69 (2H, s), 7.36-7.52 (5H, m);13C NMR δ 12.96 (CH3), 37.12 (CH2), 38.55 (CH2), 128.21 (CH), 128.83 (CH), 129.02 (CH), 131.63 (Cq), 132.89 (Cq), 133.07 (Cq), 138.92 (Cq), 140.49 (Cq); MS (EI) m/z 272 (M++ 2, 17), 271 (M++ 1, 30), 270 (M+, 25), 269 (36), 234 (64), 185 (100).
Data for 3,4-Bis(chloromethyl)-2,5-diphenylthiophene (4d): white solid; 64% yield; mp 108.1-108.7 °C;1H NMR δ
4.76 (4H, s), 7.42-7.61 (10H, m); 13C NMR δ 38.45 (CH
2), 128.55 (CH), 128.94 (CH), 129.08 (CH), 132.50 (Cq), 132.58 (Cq), 143.22 (Cq); MS (EI) m/z 336 (M++ 3, 4), 335 (M++ 2, 7), 334 (M++ 1, 27), 333 (M+, 17), 332 (42), 298 (20), 297 (47), 248 (100), 247 (62), 129 (69). Anal. Calcd for C18H14Cl2S: C, 64.87; H, 4.23. Found: C, 64.70; H, 4.62.
General Procedure for the Synthesis of 5,7-Disubsti-tuted 1,4-Dihydro-1H-3λ4 -thieno[3,4-d][2,3]oxathiin-3-oxides (Sultines) 5a-d. A solution of 4a-d (0.30 g for 4a, 1.43 mmol), Rongalite (0.44 g, 2.86 mmol), and TBAB (0.69 g, 2.15 mmol) in DMF (50 mL) was stirred at room temperature
for 2 h. The mixture was diluted with H2O (40 mL) and
extracted three times (3× 20 mL) with ether. The organic
layer was dried over MgSO4, concentrated, and purified by column chromatography (25-5:1 hexane/ethyl acetate) to give 0.14 g (0.67 mmol, 47%) of 5a. Corresponding yields for other
) 16.1 Hz), 4.94 (1H, AB, J ) 14.9 Hz), 5.08 (1H, AB, J ) 14.9 Hz); 13C NMR δ 49.50 (CH 2), 57.04 (CH2), 120.44 (Cq), 121.23 (Cq), 125.51 (Cq), 126.36 (Cq); MS (EI) m/z 242 (M+, 11.4), 178 (M+- SO 2, 100); HRMS m/z calcd for C6H4Cl2O2S2 241.9030, found 241.9024. Anal. Calcd for C6H4Cl2O2S2: C, 29.64; H, 1.66. Found: C, 29.66; H, 1.94.
Data for 7-Methyl-5-phenyl-1,4-dihydro-1H-3λ4 -thieno-[3,4-d][2,3]oxathiin-3-oxide (Sultine 5c): pale yellow solid; mp 91-92 °C;1H NMR δ 2.41 (3H, s), 3.79 (1H, A′B′, J ) 15.5 Hz), 4.15 (1H, A′B′, J ) 15.5 Hz), 5.05 (1H, AB, J ) 14.0 Hz), 5.26 (1H, AB, J ) 14.0 Hz), 7.35-7.45 (5H, m);13C NMR δ 12.71 (CH3), 51.59 (CH2), 58.81 (CH2), 121.02 (Cq), 126.42 (Cq), 127.79 (CH), 128.40 (CH), 128.94 (CH), 133.00 (Cq), 135.01 (Cq), 136.02 (Cq); MS (EI) m/z 264 (M+, 5), 200 (M+- SO2, 96), 119 (96), 185 (M+ - SO 2 - CH3, 100); HRMS m/z calcd
for C13H12O2S2 264.0279, found 264.0280. Anal. Calcd for C13H12O2S2: C, 59.07; H, 4.58. Found: C, 59.32; H, 4.71.
Data for 5-Methyl-7-phenyl-1,4-dihydro-1H-3λ4 -thieno-[3,4-d][2,3]oxathiin-3-oxide (Sultine 5c′): pale yellow solid; mp 95-97 °C;1H NMR δ 2.37 (3H, s), 3.60 (1H, A′B′, J ) 15.6 Hz), 4.05 (1H, A′B′, J ) 15.6 Hz), 5.03 (1H, AB, J ) 14.1 Hz), 5.44 (1H, AB, J ) 14.1 Hz), 7.29-7.46 (5H, m);13C NMR δ 12.59 (CH3), 51.54 (CH2), 58.75 (CH2), 121.04 (Cq), 126.42 (Cq), 127.71 (CH), 128.33 (CH), 128.86 (CH), 132.96 (Cq), 134.93 (Cq), 135.91 (Cq); MS (EI) m/z 264 (M+, 6), 200 (M+- SO2, 78), 199 (100), 185 (75).
Data for 5,7-Diphenyl-1,4-dihydro-1H-3λ4 -thieno[3,4-d][2,3]oxathiin-3-oxide (Sultine 5d): clear crystal after recrystallization from a solvent of CH2Cl2and hexane; mp 176-177 °C;1H NMR δ 3.80 (1H, A′B′, J ) 15.6 Hz), 4.36 (1H, A′B′, J ) 15.6 Hz), 5.16 (1H, AB, J ) 14.0 Hz), 5.49 (1H, AB, J ) 14.0 Hz), 7.37-7.49 (10H, m);13C NMR δ 53.22 (CH 2), 59.43 (CH2), 121.22 (Cq), 127.78 (Cq), 128.24 (CH), 128.31 (CH), 128.66 (CH), 128.95 (CH), 129.00 (CH), 129.05 (CH), 132.59 (Cq), 132.67 (Cq), 137.87 (Cq), 140.95 (Cq); MS (EI) m/z 326 (M+, 1.5), 262 (34), 261 (100), 228 (28); HRMS m/z calcd for C18H14O2S2 326.0436, found 326.0433. Anal. Calcd for C18H14O2S2: C, 66.23; H, 4.32. Found: C, 66.18; H, 4.39.
General Procedure for the Trapping Experiments of 2,5-Dimethylthienosultine 5a with Dienophiles Such as N-Phenylmaleimide, Dimethyl Fumarate, and Fuma-ronitrile. A solution of 2,5-dimethylthienosultine 5a (50 mg, 0.25 mmol), with or without the respective dienophiles (0.74 mmol), in benzene (3 mL) was kept in a sealed tube at 180 °C for 24 h. The solvent was evaporated under vacuum, and the residue was subjected to silica gel chromatography using hexane/ethyl acetate (from 16:1 to 4:1) as the eluent. Sulfolene 6a was obtained in 90% yield (no quencher). For the trapping by dienophiles, the respective yields are as follows: N-phenylmaleimide, 6% 6a and 91% 8a; dimethyl fumarate, 49% 6a and 40% 9a; fumaronitrile, 46% 6a and 43% 10a.
Data for 4,6-Dimethyl-1,3-dihydro-1H-2λ6
-thieno[3,4-c]thiophene-2,2-dione (6a): white solid; mp 187-188 °C;1H
NMR δ 2.34 (6H, s), 4.11 (4H, s);13C NMR δ 13.54 (CH 3), 54.71 (CH2), 126.59 (Cq), 133.57 (Cq); MS (EI) m/z 202 (M+, 21.7), 138 (M+- SO2, 100); HRMS m/z calcd for C8H10O2S2202.0122, found 202.0119. Anal. Calcd for C8H10O2S2: C, 47.50; H, 4.98. Found: C, 47.29; H, 5.06.
Data for 1,3-Dimethyl-6-phenyl-4a,5,6,7,7a,8-hexahy-dro-4H-thieno[3,4-f]isoindole-5,7-dione (8a): white solid;
mp 149-151 °C;1H NMR δ 2.20 (6H, s), 2.57-2.63 (2H, m), 3.12-3.18 (2H, m), 3.20-3.30 (2H, m), 6.82-6.86 (2H, m), 7.24-7.33 (3H, m);13C NMR δ 12.14 (CH 3), 24.47 (CH2), 40.23 (CH), 126.38 (CH), 128.51 (CH), 129.01 (CH), 129.24 (Cq), 130.64 (Cq), 131.78 (Cq), 178.77 (Cq); MS (EI) m/z 311 (M+, 100), 163 (60); HRMS m/z calcd for C18H17NO2S 311.0980, found 311.0984.
Data for Dimethyl (5R*,6R*)-1,3-Dimethyl-4,5,6,7-tet-rahydrobenzo[c]thiophene-5,6-dicarboxylate (9a): white solid; mp 106-108 °C;1H NMR δ 2.17 (6H, s), 2.21-2.48 (2H, m), 2.84-2.97 (4H, m), 3.66 (6H, s);13C NMR δ 12.46 (CH
3), 27.70 (CH2), 42.68 (CH), 50.00 (CH3), 128.37 (Cq), 130.58 (Cq), 175.13 (Cq); MS (EI) m/z 282 (M+, 71.0), 222 (67), 163 (100); HRMS m/z calcd for C14H18O4S 282.0926, found 282.0921. Anal. Calcd for C14H18O4S: C, 59.55; H, 6.43. Found: C, 59.19; H, 6.38.
Data for (5R*,6R*)-1,3-Dimethyl-4,5,6,7-tetrahydroben-zo[c]thiophene-5,6-dicarbonitrile (10a): white solid; mp 214-215 °C;1H NMR δ 2.92 (6H, s), 2.87-2.95 (2H, m), 3.11-3.27 (4H, m);13C NMR δ 12.58 (CH 3), 26.74 (CH2), 28.87 (CH3), 118.55 (Cq), 126.30 (Cq), 130.58 (Cq); MS (EI) m/z 216 (M+, 21.7), 138 (100); HRMS m/z calcd for C12H12N2S 216.0727, found 216.0722.
General Procedure for the Trapping Experiments of 2,5-Dichlorothienosultine 5b with Dienophiles Such as N-Phenylmaleimide, Dimethyl Fumarate, and Fuma-ronitrile. A solution of 2,5-dichlorothienosultine 5b (50 mg, 0.21 mmol), with or without the respective dienophiles (0.62 mmol), in benzene (3 mL) was kept in a sealed tube at 180 °C for 24 h. The solvent was evaporated under vacuum, and the residue was subjected to silica gel chromatography using 25:1 hexane/ethyl acetate as the eluent. Sulfolene 6b was obtained in 95% yield (no quencher). For the trapping by dienophiles, the respective yields are as follows: N-phenylmaleimide, 7% 6b and 65% 8b; dimethyl fumarate, 4% 6b and 64% 9b; fumaronitrile, 16% 6b and 77% 10b.
Data for 4,6-Dichloro-1,3-dihydro-1H-2λ6 -thieno[3,4-c]-thiophene-2,2-dione (6b): white solid; mp 157-160 °C;1H NMR δ 4.22 (4H, s);13C NMR δ 55.09 (CH
2), 123.07 (Cq), 128.05 (Cq); MS (EI) m/z 242 (M+, 18.5), 178 (M+- SO2, 100); HRMS
m/z calcd for C6H4Cl2O2S2 241.9030, found 241.9039. Anal. Calcd for C6H4Cl2O2S2: C, 29.64; H, 1.66. Found: C, 29.66; H, 1.94.
Data for 1,3-Dichloro-6-phenyl-4a,5,6,7,7a,8-hexahy-dro-4H-thieno[3,4-f]isoindole-5,7-dione (8b): white solid;
mp 195-196 °C;1H NMR δ 2.77-2.85 (2H, m), 3.31-3.46 (4H,
m), 7.06-7.09 (2H, m), 7.36-7.45 (3H, m);13C NMR δ 24.06 (CH2), 39.24 (CH), 121.26 (Cq), 126.18 (CH), 128.69 (CH), 129.10 (CH), 131.49 (Cq), 131.84 (Cq), 177.52 (Cq); MS (EI) m/z 351 (M+, 100), 169 (52), 134 (47); HRMS m/z calcd for C16H11 -SO2Cl2N 350.9987, found 350.9887. Anal. Calcd for C16H11SO2 -Cl2N: C, 54.56; H, 3.15; N, 3.98. Found: C, 54.57; H, 3.54; N, 4.09.
Data for Dimethyl (5R*,6R*)-1,3-Dichloro-4,5,6,7-tet-rahydrobenzo[c]thiophene-5,6-dicarboxylate (9b): white solid; mp 88-89 °C;1H NMR δ 2.52-2.71 (2H, m), 2.93-3.15 (4H, m), 3.75 (6H, s);13C NMR δ 26.77 (CH 2), 41.57 (CH), 52.23 (CH3), 120.56 (Cq), 131.81 (Cq), 174.03 (Cq); MS (EI) m/z 322 (M+, 55.1), 262 (100), 203 (99), 168 (74); HRMS m/z calcd for C12H12SO4Cl2321.9833, found 321.9828. Anal. Calcd for C12H12 -SO4Cl2: C, 44.60; H, 3.74. Found: C, 44.65; H, 3.89.
Data for (5R*,6R*)-1,3-Dichloro-4,5,6,7-tetrahydroben-zo[c]thiophene-5,6-dicarbonitrile (10b): white solid; mp 192-194 °C;1H NMR δ 3.00-3.21 (4H, m), 3.35-3.39 (2H, m);
13C NMR δ 25.84 (CH
2), 27.86 (CH), 117.53 (Cq), 123.02 (Cq), 127.72 (Cq); MS (EI) m/z 256 (M+, 85.4), 178 (100); HRMS m/z calcd for C10H6Cl2N2S 255.9629, found 255.9633.
General Procedure for the Trapping Experiments of 2-Methyl-5-phenylthienosultine 5c with Dienophiles Such as N-Phenylmaleimide, Fumaronitrile, Dimethyl
Acet-ylenedicarboxylate, and Diethyl Fumarate. A solution of 2-methyl-5-phenylthienosultine 5c (50 mg, 0.189 mmol), with or without the respective dienophiles (0.567 mmol), in toluene (3 mL) was kept in a sealed tube at 180 °C for 24 h. The solvent was evaporated under vacuum, and the residue was subjected to silica gel chromatography using hexane/ethyl acetate (from 6:1 to 4:1) as the eluent. Sulfolene 6c was obtained in 98% yield (no quencher). For the trapping by dienophiles, the respective yields are as follows: N-phenylmaleimide, 16% 6c and 76% 8c; fumaronitrile, 13% 6c and 75% 10c; dimethyl acetylenedicarboxylate, 47% 6c and 37% 11c; diethyl fuma-rate, 23% 6c and 69% 12c.
Data for 4-Methyl-6-phenyl-1,3-dihydro-1H-2λ6 -thieno-[3,4-c]thiophene-2,2-dione (6c): clear crystal; mp 197-198 °C (CH2Cl2/hexane);1H NMR δ 2.44 (3H, s), 4.17 (2H, s), 4.38 (2H, s), 7.44-7.32 (5H, m); 13C NMR δ 13.89 (CH 3), 53.89 (CH2), 56.21 (CH2), 125.69 (Cq), 126.88 (CH), 127.98 (CH), 128.37 (Cq), 129.13 (CH), 132.94 (Cq), 133.78 (Cq), 136.67 (Cq); MS (EI) m/z 265 (M++ 1, 3), 264 (M+, 25), 200 (M+- SO 2, 100), 199 (80), 185 (M+- SO 2- CH3, 64), 184 (53); HRMS
m/z calcd for C13H12O2S2264.0279, found 264.0278. Anal. Calcd for C13H12O2S2: C, 59.07; H, 4.58. Found: C, 59.13; H, 4.67. Data for 1-Methyl-3,6-diphenyl-4a,5,6,7,7a,8-hexahy-dro-4H-thieno[3,4-f]isoindole-5,7-dione (8c): yellow oil;1H NMR δ 2.38 (3H, s), 2.76-2.88 (2H, m), 3.29-3.58 (4H, m), 6.95-6.98 (2H, m), 7.29-7.42 (8H, m);13C NMR δ 12.37 (CH 3), 24.32 (CH2), 24.94 (CH2), 40.11 (CH), 126.33 (CH), 127.26 (CH), 128.60 (CH), 128.68 (CH), 129.04 (CH), 130.46 (Cq), 131.77 (Cq), 131.95 (Cq), 132.30 (Cq), 133.60 (Cq), 134.89 (Cq), 178.54 (Cq), 178.63 (Cq); MS (EI) m/z 374 (M++ 1, 18), 373 (M+, 100), 225 (40), 187 (14); HRMS m/z calcd for C23H19NO2S 373.1137, found 373.1136.
Data for (5R*,6R*)-1-Methyl-3-phenyl-4,5,6,7-tetrahy-drobenzo[c]thiophene-5,6-dicarbonitrile (10c): pale yel-low solid; mp 158.2-160.0 °C;1H NMR δ 2.37 (3H, s), 2.97-3.40 (6H, m), 7.26-7.45 (5H, m);13C NMR δ 12.87 (CH 3), 26.81 (CH2), 28.10 (CH2), 28.76 (CH), 29.03 (CH), 118.32 (Cq), 118.55 (Cq), 126.40 (Cq), 127.39 (Cq), 127.63 (CH), 128.44 (CH), 128.82 (CH), 133.38 (Cq), 133.68 (Cq), 135.75 (Cq); MS (EI) m/z 278 (M+, 100), 199 (57), 185 (45), 165 (26); HRMS m/z calcd for C17H14N2S 278.0879, found 278.0871.
Data for Dimethyl 1-Methyl-3-phenyl-4,7-dihydroben-zo[c]thiophene-5,6-dicarboxylate (11c): yellow solid; mp 101-102 °C;1H NMR δ 2.40 (3H, s), 3.54-3.75 (4H, m), 3.79 (3H, s), 3.83 (3H, s), 7.28-7.45 (5H, m); 13C NMR δ 12.95 (CH3), 27.25 (CH2), 29.00 (CH2), 52.42 (CH3), 127.12 (CH), 128.41 (CH), 128.71 (CH), 129.80 (Cq), 131.78 (Cq), 131.93 (Cq), 133.84 (Cq), 134.23 (Cq), 168.19 (Cq), 168.71 (Cq); MS (EI) m/z 342 (M+ , 77), 310 (100), 309 (65), 282 (34), 251 (44), 224 (87); HRMS m/z calcd for C19H18O4S 342.0926, found 342.0929.
Data for Diethyl (5R*,6R*)-1-Methyl-3-phenyl-4,5,6,7-tetrahydrobenzo[c]thiophene-5,6-dicarboxylate (12c): pale yellow solid; mp 72-73 °C;1H NMR δ 1.19-1.32 (6H, m), 2.34 (3H, s), 2.83-3.18 (6H, m), 4.10-4.23 (4H, m), 7.27-7.40 (5H, m);13C NMR δ 12.82 (CH 3), 14.09 (CH3), 14.15 (CH3), 27.70 (CH2), 29.41 (CH2), 42.70 (CH), 43.08 (CH), 60.82 (CH2), 126.93 (CH), 128.37 (CH), 128.57 (CH), 130.93 (Cq), 131.65 (Cq), 131.87 (Cq), 133.48 (Cq), 134.29 (Cq), 174.56 (Cq), 174.63 (Cq); MS (EI) m/z 372 (M+, 46), 327 (11), 298 (20), 225 (100); HRMS m/z calcd for C21H24O4S 372.1395, found 372.1395.
General Procedure for the Trapping Experiments of 2,5-Diphenylthienosultine 5d with Dienophiles Such as N-Phenylmaleimide, Dimethyl Fumarate, Fumaroni-trile, and Diethyl Fumarate. A solution of 2,5-diphenyl-thienosultine 5d (50 mg, 0.153 mmol), with or without the respective dienophiles (0.459 mmol), in toluene (3 mL) was kept in a sealed tube at 180 °C for 24 h. The solvent was evaporated under vacuum, and the residue was subjected to silica gel chromatography using hexane/ethyl acetate (from 10:1 to 6:1) as the eluent. Sulfolene 6d was obtained in 94% yield (no quencher). For the trapping by dienophiles, the respective yields are as follows: N-phenylmaleimide, 6% 6d
3.59-3.64 (2H, dd, J ) 14.7, 6 Hz), 6.99-7.02 (2H, m), 7.34-7.52 (13H, m); 13C NMR δ 24.91 (CH 2), 40.16 (CH), 126.42 (CH), 127.75 (CH), 128.74 (CH), 128.88 (CH), 129.24 (CH), 131.55 (Cq), 131.77 (Cq), 133.32 (Cq), 137.85 (Cq), 178.58 (Cq); MS (EI) m/z 436 (M++ 1, 11), 435 (M+, 100), 287 (16), 286 (20), 261 (13); HRMS m/z calcd for C28H21NO2S 435.1294, found 435.1285. Anal. Calcd for C28H21NO2S: C, 77.22; H, 4.86; N, 3.22. Found: C, 77.20; H, 5.04; N, 3.41.
Data for Dimethyl (5R*,6R*)-1,3-Diphenyl-4,5,6,7-tet-rahydrobenzo[c]thiophene-5,6-dicarboxylate (9d): white solid; mp 184-185 °C;1H NMR δ 2.90-3.05 (4H, m), 3.24-3.30 (2H, m), 3.71 (6H, s), 7.29-7.49 (10H, m); 13C NMR δ 29.14 (CH2), 42.79 (CH), 52.08 (CH3), 127.42 (CH), 128.52 (CH), 128.66 (CH), 131.57 (Cq), 133.88 (Cq), 136.52 (Cq), 174.89 (Cq); MS (EI) m/z 406 (M+, 34), 346 (10), 287 (100), 252 (34); HRMS
m/z calcd for C24H22O4S 406.1240, found 406.1243. Anal. Calcd for C24H22O4S: C, 70.91; H, 5.45. Found: C, 71.10; H, 5.49.
Data for (5R*,6R*)-1,3-Diphenyl-4,5,6,7-tetrahydroben-zo[c]thiophene-5,6-dicarbonitrile (10d): due to the severe overlap of 10d with 6d in column chromatography, we obtained only proton NMR data, δ 3.19-3.48 (6H, m), 7.36-7.49 (10H, m).
Data for Diethyl (5R,6R)-1,3-Diphenyl-4,5,6,7-tetrahy-drobenzo[c]thiophene-5,6-dicarboxylate (12d): white solid;
mp 145-146 °C;1H NMR δ 1.25 (6H, t, J ) 7.1 Hz), 2.90-3.04 (4H, m), 3.24-3.29 (2H, dd, J ) 15, 2.7 Hz), 4.17 (4H, q, J ) 7.1 Hz), 7.32-7.49 (10H, m);13C NMR δ 14.07 (CH 3), 29.16 (CH2), 42.95 (CH), 60.85 (CH2), 127.38 (CH), 128.52 (CH), 128.65 (CH), 131.74 (Cq), 133.95 (Cq), 136.45 (Cq), 174.43 (Cq); MS (EI) m/z 435 (M++ 1, 9), 434 (M+, 59), 287 (100), 286 (79), 253 (46); HRMS m/z calcd for C26H26O4S 434.1553, found 434.1553. Anal. Calcd for C26H26O4S: C, 71.86; H, 6.03. Found: C, 72.07, H, 6.14.
Reaction of 5b with n-BuLi Followed by Quenching with H2O or D2O To Give Products 17 and 18. To a 25 mL two-necked bottle were added 100 mg (0.42 mmol) of 5b and 5 mL of dry THF. The solution was cooled to -78 °C, 248 µL (0.62 mmol) of nBuLi was added via syringe, and the resulting solution was stirred at this temperature for 1 h. It was then stirred at 0 °C for 1 h and at rt for another 1 h. The solution was quenched with either brine (1 mL) or D2O (1 mL) in an ice bath, and the product was extracted with ethyl ether (3× 5 mL). The combined organic extracts were washed with water (2× 5 mL) and brine (5 mL) and then dried with MgSO4. The solvent was evaporated under vacuum, and the residue was subjected to silica gel chromatography using hexane/ethyl acetate (4:1) as the eluent to yield 42 mg (0.14 mmol) of 17 or 60 mg (0.20 mmol) of 18.
Data for 4-[(Butylsulfinyl)methyl]-2,5-dichloro-3-thi-enylmethanol (17): 33% yield; white solid; mp 85-86 °C;1H NMR δ 0.98 (3H, t, J ) 7.5 Hz), 1.46-1.60 (2H, m); 1.73-1.84 (2H, m); 2.47 (2H, t, J ) 7.2 Hz), 3.94, 4.10 (2H, AB, J ) 14.0 Hz), 4.49 (2H, d, J ) 6.9 Hz), 4.70 (1H, t, J ) 6.6 Hz);13C NMR δ 13.63 (CH3), 21.99 (CH2), 24.55 (CH2), 48.59 (CH2), 51.07 (CH2), 55.50 (CH2), 125.80 (Cq), 126.18 (Cq), 127.06 (Cq), 138.68 (Cq); MS (EI) m/z 301 (M+ + 1, 7), 117 (100); HRMS
m/z calcd for C10H14S2O2Cl2299.9812, found 299.9804; Rf)
0.1 (hexane:ethyl acetate ) 4:1).
a sealed tube at 180 °C for 24 h. The solvent was evaporated under vacuum, and the residue was subjected to silica gel chromatography using hexane/ethyl acetate (from 16:1 to 1:1) as the eluent. The trapping yields are as follows: 21% 19 and 30% 6a by 2-mercaptoethanol, 19% 20 and 20% 6a by
methanol, 37% 21 and 26% 6a by methanol-d4, and 86%
sulfolene 6a by 1,4-cyclohexadiene.
Data for 2-[(2,4,5-Trimethyl-3-thienyl)methyl]sulfanyl-1-ethanol (19): colorless liquid;1H NMR δ 2.14 (3H, s), 2.28 (3H, s), 2.35 (3H, s), 2.69 (2H, t, J ) 5.7 Hz); 3.60 (2H, s),
3.68-3.88 (2H, br s);13C NMR δ 12.43 (CH
3), 13.05 (CH3), 13.16 (CH3), 27.79 (CH2), 34.93 (CH2), 60.45 (CH2), 129.21 (Cq), 131.28 (Cq), 132.27 (Cq); MS (EI) m/z 216 (M+, 10), 139 (100); HRMS m/z calcd for C10H16OS2216.0643, found 216.0639.
Data for 3-(Methoxymethyl)-2,4,5-trimethylthiophene (20): colorless liquid;1H NMR δ 2.07 (3H, s), 2.27 (3H, s), 2.38 (3H, s), 3.33 (3H, s), 4.27 (2H, s);13C NMR δ 12.10 (CH
3), 12.80 (CH3), 12.89 (CH3), 57.56 (CH3), 66.27 (CH2) 128.74 (Cq), 132.93 (Cq), 133.49 (Cq), 133.58 (Cq); MS (EI) m/z 170 (M+, 1), 138 (100); HRMS m/z calcd for C9H14OS 170.0765, found 170.0763. Data for
3-(Methoxy-d3-methyl)-2,5-dimethyl-4-methyl-d1-thiophene (21): colorless liquid;1H NMR δ 2.05 (2 H, t, J
) 2.1 Hz), 2.27 (3H, s), 2.38 (3H, s), 4.26 (2H, s);13C NMR δ 11.88 (t, JCD) 20 Hz, CH2D), 12.84 (CH3), 12.93 (CH3), 66.19 (CH2) 128.78 (Cq), 132.91 (Cq), 133.53 (Cq); MS (EI) m/z 174 (M+, 23), 139 (60), 84 (100); HRMS m/z calcd for C9H10D4OS 174.1017, found 170.1017.
Procedure for the Concentration-Dependent Trap-ping of Thienosultine 5a and Furanosulfolene 16 by Fumaronitrile. Stock solutions of 5a and 16 were first prepared by adding 60 mg (0.30 mmol) of 5a to 18 mL of toluene or 45 mg (0.28 mmol) of 16 to 18 mL of benzene. The stock solution was then equally divided into six thick-walled tubes, and each contained a 3 mL solution of 5a (16.5 mM) in toluene or 16 (15.8 mM) in benzene. Tubes a and b were without fumaronitrile, and tubes c-f were with different amounts of fumaronitrile: (c) 4 mg (0.05 mmol, 16.7 mM), (d) 20 mg (0.26 mmol), (e) 40 mg (0.51 mmol), (f) 60 mg (0.77 mmol). After three cycles of freeze-pump-thaw, these tubes were sealed under vacuum, all reacted at the same time in an oil bath thermostated at (1) 150 ( 2 °C, 5 h for 5a, and (2) 120 ( 2 °C, 2 h for 16, and then cooled to room temperature. The solvent of these tubes was removed by rotary evaporation,
and to each of them was added 1 mL of CDCl3with 50 mM
N-phenylmaleimide as internal standard for1H NMR analysis. The data shown in Figure 1 are the average of at least two runs.
Acknowledgment. We thank the National Science
Council of the Republic of China for financial support
(Grant No. NSC89-2113-M-009-026).
Supporting Information Available: 1H and 13C (or DEPT) NMR spectra for compounds 8a, 8c, 10a-d, 11c, 12c, and 17-21. This material is available free of charge via the Internet at http://pubs.acs.org.
