Background and Originality Content
Chalcogenosulfonates-a class of popular chemical reagents-are commonly used in organic chemistry mainly because they have broad structural diversity, and unique chemical reactivity.[1]Further, they show diverse biological properties such as antimicrobial and antifungal activities(Scheme 1a).[2] In particular, thiosulfonates and selenosulfonates have attracted considerable research interest for the construction of novel sulfur- or selenium-containing compounds(Scheme 1b).[3] For example, by using chalcogenosulfonates as bifunctional reagents, various chalcogenative compounds that contain a two-carbon unit with a heteroatom bonded to each carbon, have been prepared.[4] Although chalcogenosulfonates have played a notable role in the design of biological active molecules and the development of novel reactions, their further application is mainly restricted by rare access to structurally novel chalcogenosulfonates, such as heteroaryl-substituted or biorelevant chalcogenosulfonates.
Scheme 1 (a) Representative bioactive chalcogenosulfonates and (b) general reaction modes of chalcogenosulfonates
Generally, the strategies for synthesizing thiosulfonates involve two types of reactions. One method usually relies on the use of substrates bearing an S–S bond. Examples include the oxidation of disulfides or thiosulfinates, the nucleophilic substitution of alkali metal thiosulfonates with alkyl halides, oxiranes or alkenyliodonium salts.[5] These methods, however, have many limitations such as the need for prefunctionalized starting materials, the use of stoichiometric amounts of oxidants and a narrow substrate scope. Furthermore, only thiosulfonates could be obtained by this method. The second approach mainly involves the condensation of sulfonyl derivatives with other organosulfur/organoselenium precursors.[6] However, because of the toxic reagents, harsh reaction conditions, and the limited availability of organosulfur/organoselenium precursors, the use of the safe and abundant sulfur/selenium powder is highly desirable. In addition, the available techniques are generally limited to synthesizing thiosulfonates or selenosulfonates, whereas methods to produce sulfonotelluroates remain rare because the formed C–Te bond can be easily cleaved by metal catalysts, acids, organolithium reagents, etc.[7]Further, the synthesis of chalcogenosulfonates continues to be very challenging. Thus, because of these challenges coupled with the increasing importance of chalcogenosulfonates, synthetic chemists are motivated to develop mild, general methods that (i) enable efficient incorporation of the simple chalcogen into the sulfonyl group to form the SO2-X (X = S, Se, Te) bond under transition-metal-, acid-, external-oxidant-free conditions; and that (ii) are suitable for the facile synthesis of structurally diverse chalcogenosulfonates and for late-stage modification of biorelevant compounds.
Organic electrochemistry, in which redox processes are driven with electric current instead of chemical oxidants or reductants,[8] is being increasingly considered in the past few years for sustainable synthesis owing to its inherent environmental friendliness, sustainability and tunability.[9] Electrochemically catalyzed multicomponent reactions involving three or more reactants in a one-pot operation with the incorporate substantial portions of all the components into the same products,[10] are green and efficient and have been used for the construction of chalcogenated organic compounds.[11] The synthesis of chalcogenosulfonates, however, by electrochemically catalyzed multicomponent reactions has not been realized. Given the importance of chalcogenosulfonates in the pharmaceutical industry and organic synthesis, in this study, a simple and efficient method was developed for the preparation of chalcogenosulfonates from indoles, sulfinic acid sodium salts and the simple chalcogen, and sulfonotelluroates were synthesized for the first time via an electrocatalytic three-component reaction.
Scheme 2 Research background and our new observation
Results and Discussion
At the outset of the investigation, Indole 1a , sodiump -toluenesulfinate 2a and selenium powder were selected as model substrates (Table 1). After we analyzed a range of reaction parameters, we discovered that the application of TBAI (n-Bu4NI) as the mediator and supporting electrolyte in a 3:1 mixture of MeCN and H2O with a carbon rod anode and carbon rod cathode under a constant current (10.0 mA) at room temperature furnished the selenosulfonate 3aa in 89% yield (entry 1). The screening of the reaction media revealed that a mixture of MeCN and H2O (2:1) was the most suitable solvent for this transformation (entries 2—6). Other mediators, such as NaI, KI and n-Bu4NBr, were also well compatible with the present catalytic reaction delivering the desired product 3aa in moderate yields (entry 7). Different electrode materials and electric current values did not improve the reaction efficiency (entries 8—11). A shorter reaction time resulted in 71% yield of the product 3aa (entry 12). Only a trace amount of product could be detected when the reaction was performed under an air atmosphere (entry 13). Control experiments revealed that TBAI or electricity was indispensable, confirming the electrochemical nature of this three-component reaction (entries 14 and 15). The reaction was scaled up to a 10-mmol scale, and 72% yield of the desired product 3aa was obtained by using a single-batch reaction setup (entry 16).
Table 1 Optimization of the reaction conditionsa