Catalyzed Efficient , Regio-and Chemoselectively Synthesis of-Hydroxy Thioethers from Aryl Disulfides in the Presence of Zinc Powder

Um método novo e conveniente foi desenvolvido para a síntese de -tioéteres com disulfetos arílicos e zinco em pó, na presença catalítica de Bi(OTf) 3 e Bi(TFA) 3 em acetonitrila. O presente método é bastante simples e tolera uma variedade de grupos ácidos protetores. Entretanto, disulfetos arílicos e benzílicos não fornecem os correspondentes tioéteres nas mesmas condições. Assim, a regioe quimiosseletividade observada pode ser apontada como uma vantagem destacada deste método.


Introduction
Ring-opening reaction of epoxides with nucleophiles has been widely used to the preparation of some starting materials that are very important in organic synthesis.Among them thiolyzation of epoxides has attracted much attention because it produces -hydroxy thioethers as valuable intermediates for the synthesis of important compounds such as -thioketones, 1 -hydroxy sulfoxides, 2,3 benzothiazepines 4 or benzoxathiepines 5 that are used as building blocks for preparation of some natural products [6][7][8][9][10] or pharmaceuticals. 11,12The classical synthesis of -hydroxy thioethers consists of heating an epoxide with an excess of unpleasant odor thiol.4][15][16][17][18][19][20][21] However, some of these methods suffer from one or more limitations including the use of stoichiometric amounts of the reagents and unpleasant odor substrates, long reaction times, unsatisfactory yields, poor selectivity, and the use of expensive and toxic reagents or catalysts.Therefore, to find out a better alternative method for synthesis of -hydroxy thioethers is desirable.
3][24][25][26] Many recent papers describing the use of bismuth compounds in organic transformations pointed out that their use is ecologically friendly.In addition, bismuth derivatives have been widely used in medicine. 27They have attracted much attention because they are easy to handle, low in cost and relatively insensitive to air and moisture. 28ery recently, we introduced bismuth (III) salts as efficient catalysts for the ring opening of epoxides with anilines, 29,30 synthesis of -enaminones, 31 dihydropyrimidones, 32 azalactones 33 and conversion of thiocarbonyls to their carbonyl compounds. 34In continuation of our interest in exploring new reactions on epoxides catalyzed with bismuth (III) salts, and due to the lack of any report on the ring opening of oxiranes with disulfides in the presence of these Lewis acids, we now report for the first time the thiolysis of oxiranes with aryl disulfides using zinc powder in the presence of 3 mol % of Bi(TFA) 3 or 1 mol % Bi(OTf) 3 in acetonitrile under reflux conditions (Scheme 1).

Results and Discussion
A variety of epoxides underwent smooth transformation to the corresponding -hydroxy thioethers in good to excellent yields when they reacted with diaryl disulfides (Table 1).Diphenyl, di-2-naphtyl and di-p-tolyl disulfides were used as aromatic disulfides in these reactions.Cyclohexene oxide as a symmetrical epoxide underwent cleavage with the aryl disulfides to produce the corresponding -hydroxy thioethers in high yields and stereo-selectivity (Table 1, entries 4-6).The products obtained from this epoxide showed the formation of trans isomer as the only product of the reaction based on 1 H NMR spectrum.The reaction of styrene oxide with diaryl disulfide afforded only one product, 2, which was formed from attack of the nucleophile at the benzylic position and its structure was also confirmed by 1 H NMR spectroscopy of the crude product (Table 1, entries 1-3).This regio-selectivity is not similar to that obtained from thiolysis of epoxides in tetrabutylammonium fluoride in which the regio-isomer 3 is the major product. 35This regioselectivity observed in these reactions seems to be controlled by electronic effects and attack of nucleophile occurs on the carbon atom which can effectively stabilize the developing positive charge.The reaction of alkyl oxirane such as 1,2-epoxyoctane with disulfides underwent in preferential attack at the less crowded side of oxirane and the corresponding -hydroxy thioether is obtained in high yield and regio-selectivity (Table 1, entry 9).
When the reaction was carried out in the absence of the Lewis acid no product obtained which shows that the presence of the Lewis acid is necessary.The reaction in the presence of catalytic amount of trifluoromethane sulfonic acid as the catalyst in acetonitrile was also examined in order to understand which of the salt (bismuth salt) or the Bronsted acid (trifluoromethane sulfonic acid) has the key role in this reaction.We found that the reaction was proceeded by CF 3 SO 3 H to afford the corresponding product in less than 1 h.However, since the solvent of the reaction is aprotic in contrast to the solvent (H 2 O/THF) used by Mohan's group 36 it seems in this conditions the Lewis acid catalyses the reaction.In other words, under this circumstance the existence of equilibrium between Bi salts and their acids is doubtful.When the same experiments were carried out using BiCl 3 and CeCl 3 , interesting results were obtained.The reaction in the presence of CeCl 3 was Scheme 1. a All products are known compounds and characterized by comparison of their 1 H NMR, 13 C NMR, IR spectral data with those reported in literature; 35,18,38 b Isolated yields.
not performed but, the reaction in the presence of BiCl 3 underwent well and gave the same products which shows that the Lewis acid catalyses the reaction.However, since the catalytic amount of trifluoromethane sulfonic acid could also catalyze the reaction under the same reaction conditions, the role of this acid in the reaction can not be eliminated completely.This may be explained by the fact that the used acetonitrile was not completely dried.In these reactions 1 mol % of Bi(OTf) 3 is sufficient to be effective but in the case of Bi(TFA) 3 , 3 mol % of the

Table 1 .
Regioselective ring opening of epoxides with aryl disulfides and zinc powder by Bi(OTf) 3 and Bi(TFA) 3 in actonitrile

Table 2 .
Competitive reaction of epoxides wih aryl disulfides catalyzed by Bi(III) salts