Multicomponent Cyclization with an Inorganic Sulfur Dioxide Surrogate: Straightforward Construction of Difluorinated Benzosultams

Abstract

A straightforward three-component transformation for the preparation of functionalized benzosultams under TM-free and mild reaction conditions was described, in which easy-to-handle Na2S2O5, available bromodifluoroalkyl reagent, and N-(2-haloaryl) cyanamide were employed. Na2S2O5 was essential to the generation of difluoroalkyl radical, SO2 fixation, and cyclization, which enabled efficient construction of target products in a sustainable manner. A broad substrate scope and modular feature made this protocol attractive for exploring the chemical space of the construction of cyclic sulfonamides.

Advances in the Synthesis of Sulfur-Containing Cyclic Architectures via Insertion of SO2

“…In 2022, Liao and coworkers disclosed a straightforward three-component coupling for the preparation of functionalized benzosultams 23 under transition metal-free and mild reaction conditions with the employment of readily available and environmental-friendly Na2S2O5, available bromodifluoroalkyl reagents 22, and N-(2-haloaryl) cyanamides 21 (Scheme 10) 15 . Diverse five-membered and six-membered embedded (A ring) difluorinated benzosultams 23 could be efficiently synthesized in good to excellent yields under the guidance of this protocol.…”

“…Their method employed readily available and environmentally friendly Na 2 S 2 O 5 , readily obtainable bromodifluoroalkyl reagents 22 , and N -(2-haloaryl)cyanamides 21 (Scheme 9 ). 15 Diverse five-membered- and six-membered-embedded (A ring) difluorinated benzosultams 23 could be efficiently synthesized in good to excellent yields by utilizing this protocol. The reactivity of cyanamides 21 substituted with different halogen atoms was investigated under the standard conditions, and the results suggested that 2-bromo- and 2-chloro-substituted analogues gave the desired products in diminished yields compared with their N -(2-iodoaryl)cyanamide counterparts.…”

“…The mechanism indicated that Na 2 S 2 O 5 first generated a SO 2 radical anion which reduced 22 via an SET process to produce a difluoroalkyl radical ( • R f ) and released SO 2 . 15 The difluoroalkyl radical then added to the carbon–carbon double bond of substrate A resulting in formation of the radical intermediate B (n = 1), which cyclized via intramolecular addition of the C-radical to the cyano group to give iminyl radical intermediate C . The desired product F would be formed through a series of transformations after capture of SO 2 by the iminyl species C .…”

Difunctionalization of Dienes, Enynes and Related Compounds via Sequential Radical Addition and Cyclization Reactions

“…Liao and coworkers employed this substrate in the synthesis of functionalized benzosultams. The reaction of N -(2-haloaryl)cyanamide, bromodifluoroalkyl reagents and Na 2 S 2 O 5 in DMF and H 2 O at 80 °C afforded product 93 in good yields ( Scheme 93 ) [ 103 ]. A proposed reaction mechanism suggests that the CF 2 CO 2 Et radical derived from BrCF 2 CO 2 Et SO 2 adds to the carbon double bond of amide followed through 5- exo cyclization to the CN group, capture of SO 2 (generated from Na 2 S 2 O 5 ) to form sulfonyl radicals, cyclization to the benzene ring at the carbon with iodine, and a last step of deiodo aromatization to give product 93a .…”

A radical Smiles rearrangement difunctionalization of activated alkenes via desulfonylation and insertion of sulfur dioxide relay strategy

“…7 In recent years, the insertion of sulfur dioxide has been employed as a powerful tool to build sulfones. 8 Among them, the use of solid SO 2 surrogates, 9 such as DABSO 10 and inorganic sulfite, 11 can avoid the risk of using SO 2 gas. Because of the limitations of alkyl sulfonyl chlorides, such as being costly and hard-to-prepare, an alternative way was developed to achieve alkylsulfonylation through the trapping of alkyl radicals by SO 2 .…”