Preparation of S-containing heterocycles via novel reaction patterns of carbon disulfide with 1-lithiobutadienes and 1,4-dilithiobutadienes

Both carbophilic addition and thiophilic addition were involved in the first step intermolecular reaction of 1,4-dilithio-1,3-diene derivatives with carbon disulfide. Thus in situ generated carbophilic addition intermediates and thiophilic addition intermediates underwent a second step intramolecular carbophilic and thiophilic additions. Multiply substituted thiophenes were isolated as the results of cleavage of the C=S double bonds, while thiopyran-2-thiones were produced via cycloaddition reactions. In addition to 1,4-dilithio-1,3-dienes, monolithio reagents also showed interesting reactions with carbon disulfide. Thiophenes were also generated in the reaction of 1-lithio-1,3-dienes with carbon disulfide.


Introduction
Addition reactions of thiocarbonyl compounds including cumulated thiocarbonyl groups such as CS 2 with organolithium reagents are of fundamental interest because of two interesting points.Either carbophilic addition and thiophilic addition can be expected. 1As demonstrated in Scheme 1, the carbophilic addition (Scheme 1, type a) affords intermediates 1, lithiocarboxylates.In fact, among thiocarbonyl compounds, carbon disulfide has been accepted as the most useful substrate for the formation of carbon-carbon bonds.The thiophilic addition, which is shown as type b in Scheme 1, gives rise to the formation of intermediates 2. Since both types of additions may take place, it is still difficult to predict which type of addition will proceed.Furthermore, the reaction mechanisms are still in debate.Scheme1.Reaction patterns of CS 2 with organolithium compounds.
The second interesting point is selective application of the addition intermediates of CS 2 with organolithium compounds.3][4] In addition to the reaction with electrophiles, the addition products 1 or 2 may also react with nucleophiles such as RLi.However, surprisingly, application of this fundamental reaction with nucleophiles has not been investigated as such. 5][8][9][10][11] In order to study on the reaction of the addition intermediates 1 or 2 with nucleophiles, we used 5 as model compounds, expecting that selectivity can be improved and new types of reaction patterns can be discovered. 5As demonstrated in Scheme 3, both carbophilic addition intermediates 6 (Scheme 3, type a) and thiophilic addition intermediates 7 (Scheme 3, type b) can be expected as the first intermediate compounds.Intramolecular reactions of these intermediates may afford couples of products.Expected products are shown in Scheme 3. Similarly, both carbophilic addition and thiophilic addition can be expected in the subsequent intramolecular reactions of 6 and 7.For 6, carbophilic addition may afford cyclopentadienethiones 8 and dilithium derivative 9.A six-membered S-containing dilithium compound 10 might be expected from the thiophilic addition in 6.For 7, thiophene derivative 11 and the six-membered S-containing dilithium compound 10 may be formed via carbophilic addition.If a second thiophilic addition takes place in 7, a seven-membered compound 12 can be expected.Our recent studies have demonstrated that 1-lithiobutadiene derivatives 13 react with various organic substrates in a very much different manner from those of normal organolithium reagents. 10,12Thus, the reaction of 1-lithiobutadienes 13 with CS 2 also interested us.As demonstrated in Scheme 4, the first addition intermediates may be carbophilic addition compound 14 and/or thiophilic addition compound 15.In this paper, we would like to report our results on the reaction of CS 2 with 1,4-dilithiobutadienes and with 1-lithiobutadienes.

Results and Discussion
Carbon dioxide reacted with 1,4-dilithio-1,3-diene derivatives 5 to afford cyclopentadienones in excellent yields, as we reported in 2000. 7Since the reaction of organolithium reagents with thiocarbonyl groups may be analogous to those with carbonyl groups, the first expected product from the reaction of 5 with carbon disulfide was a thiocyclopentadienone 8.However, surpringly, no thiocyclopentadienone derivatives 8 were obtained for all the cases.Depending on the substituents of the dilithio reagents, either single products 11 or a mixture of 11 and 16 were obtained after hydrolysis of the reaction mixture (Scheme 5). 13,14No other products were obtained.The formation of thiopyran-2-thiones 16 were not expected.2) H + Scheme 5. Reaction of 1,4-dilithio-1,3-dienes with carbon disulfide.
Listed in Table 1 are results by the reaction of 1,4-dilithio-1,3-diene derivatives 5 with carbon disulfide.In cases of simply alkyl-substituted dilithio reagents 5a-d, the reactions afforded multiply substituted thiophenes 11 as the only prodcuts in most cases.Trace amount or non of thiopyran-2-thiones 16 were obtained.Interestingly, when a dilithio reagent 5e with SiMe 3 as substituents was used, not only thiophene 11e but also thiopyran-2-thione 16e was obtained.These two compounds could be easily seperated.Thiophene 11e was obtained in 36% yield while thiopyran-2-thione 16e was obtained in 45% yield.The molar ratio of these two compounds was near 4:5.Later we found that formation of 11 and 16 was also related to the structure of the dilithio reagents.Similarly substituted with alkyl groups but with a cyclic structure, the dilithio reagent 5f aslo afforded 16f from its reaction with carbon disulfide.
Although the reason for the ratio of 11 and 16 is not clear yet, it is assumed that steric effect of the substituents and structural characteristics be essential for the selectivity of formation of 11 and/or 16.Thiopyran-2-thione derivatives 16 are favored when the substituents on the dilithio compounds are larger and when the structures are lacking flexibility.As indicated in Scheme 3, lithiated intermediates 9, 10, 12 are assumed to be formed in the reactions of dilithio compounds 5 with carbon disulfide.In addition, Li 2 S and S=CLi 2 are proposed to be generated in the reaction mixture.In order to understand the reaction mechanisms, we carried out several further reactions, trying to trap these lithiated intermediates.For examples, addition of aldehydes, ketones, Me 3 SiCl, and so on to the reaction mixtures at various temperatures, however, did not give any meaningful results, except addition of MeI.Since reactions with MeI were pretty complicated, characterization of the structures of products was not easy.These results will be reported in due time.
At least three different reaction pathways have been proposed in the literature for the addition of organo-lithium and -magnesium compounds to thiocarbonyl groups. 1,2The formation of 11 may be rationalized in Scheme 3.For the formation of thiopyran-2-thione derivatives 16, both a concerted radical process 14 and the following intermediate 17 (Scheme 6) might be proposed.and/or Scheme 6.One possible pathway for the formation of thiopyran-2-thione derivatives.
Although selectivity of reaction of 1-lithiobutadienes with CS 2 was found to be worse than that of reaction of 1,4-dilithiobutadienes with CS 2 , the reaction pattern was novel.As demonstrated in Scheme 6, in addition to unknown products, thiophene compounds were also formed in these reactions.Some results are given in Figure 1.When the reaction mixture of CS 2 with monolithio compounds at low temperature was treated with MeI, Me 3 SiCl, or PhCOCl, yields of thiophene derivatives became much lower.No major expected methylated, silylated or acylated compounds were obtained.
Experimental Section General Procedures.All reactions were conducted under a slightly positive pressure of dry, prepurified nitrogen using standard Schlenk line techniques when appropriate.Unless otherwise noted, all starting materials were commercially available and were used without further purification.Diethyl ether was refluxed and distilled from sodium benzophenone ketyl under a nitrogen atmosphere.t-BuLi was obtained from Kanto Chemicals Co. Ltd.Carbon disulfide was purified before use according to a reported procedure. 15 1  and 13 C NMR spectra were recorded at 300 and 75.4 MHz, respectively, in CDCl 3 unless stated otherwise.1,4-Dilithio-1,3-diene derivatives 5 were generated in situ from their corresponding 1,4-diiodo-1,3-dienes and t-BuLi. 8 onolithio 1,3-diene derivatives 13 were produced similarly from their corresponding monoiodo 1,3-dienes.10

A typical procedure for the preparation of thiophene derivatives from monolithio-1,3-diene compounds
To a diethyl ether (5 mL) solution of monoiodo-1,3-butadiene (1 mmol) at -78 o C was added tBuLi (2.0 mmol, 1.47 M in pentane).The above reaction mixture was then stirred at -78 o C for 1 h to generate monolithio-1,3-diene 13a, which was monitored by GC analysis or by TLC.After addition of carbon disulfide (1.1 mmol) at -78 o C, the mixture was stirred at room temperature for 1h.The above reaction mixture was then quenched with 3N HCl and extracted with diethyl ether.The extract was washed with NaHCO 3 , brine and dried over MgSO 4 .The solvent was evaporated in vacuo to give a brown oil, which was purified by column chromatograph (silica gel, hexane) to afford 11b, which was exactly the same as that obtained by using dilithiobutadiene 5b as given above.In case of 13c, no major products were obtained.2,3-Dimethyl-4,5-diphenylthiophene (11g). 16,17White solid, isolated yield 58% (153 mg).mp:108-109 o C (lit. 16 Scheme2.Application of the addition intermediates of CS 2 with organolithium compounds.

a a
Reaction conditions: Shown in Scheme 5. b Isolated yields.