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