TosMIC: A Powerful Synthon for Cyclization and Sulfonylation

Abstract

p‐tosylmethyl isocyanide (TosMIC) which is also known as van Leusen's reagent hold the three functionalized groups including the isocyanide and sulfonyl group and an alpha carbon which is acidic by nature. Tosyl set of this fortunate reagent acts as a good leaving group and assist the alpha carbon to contribute in a range of cyclization strategies. Exceptionally, TosMIC was also proved as a good sulfonylating and sulfomethylating reagent. TosMIC has proved as a powerful and versatile synthon and betrothed in the synthesis of broad range of heterocycles having pharmacological interest. This review is focused on synthetic utility of TosMIC in diverse range of heterocycles like five membered heterocycles, fused heterocycles, linked or tethered heterocycles, spiro compounds etc. It is also utilized for regio, chemo and stereoselective synthesis and production of sulfones and sulfinates. It serves as an important building block in various synthetic methodologies like multi component reaction, cyclization, domino, cascade and cycloaddition and metal catalysed reactions. Various new catalyst and novel methodologies were explored due to enormous use of this wonderful reagent.

Ruthenium‐Catalyzed Sulfoalkenylation of Acetanilides and Dual‐Use of the Catalyst Directing Group

“…Due to the electron withdrawing effect of the sulfonyl and sulfonamide groups these olefins can be expected to react with deprotonated tosylmethylisocyanide (Tosmic) in a conjugated addition reaction. This transformation, which was originally developed by van Leusen et al, [63] has been widely used for the synthesis of pyrroles and other heterocycles, [64][65] but only few examples for its application to α,β-unsaturated sulfonyl compounds have been described in the literature. Padmavathi and co-workers reported the syn-thesis of pyrrole-3-sulfones [66] and pyrrole-3-sulfonamides [67] along this route.…”

Cascade synthesis of 2,4-disulfonylpyrroles by the sulfonylation/[2 + 3]-cycloaddition reactions of gem-dibromoalkenes with arylsulfonyl methyl isocyanides

“…Also, when the amount of Cs 2 CO 3 was decreased, the result reduced to 50% yield (Table 1, entry 10). Changing the reaction media to other solvents such as DMF, toluene or CH 3 CN, was not very successful to improve the product yield (Table 1, entries [11][12][13]. In fact, the reaction failed in toluene (Table 1, entry 12).…”

“…1). 12,13 Moreover, sulfonyl function as a leaving group can offer TosMIC an efficient source of sulfonyl group, whereby it can act as a dual reagent and/or as a sulfonylation reagent. 12 In this regard, Bi et al introduced the dual role of TosMIC in a cascade reaction with propargylic alcohols, wherein TosMIC acted as a reagent for allenylative and sulfonylation in the presence of Ag 2 CO 3 to give (E)-vinyl sulfones (Scheme 1, eqn (1)).…”

“…12,13 Moreover, sulfonyl function as a leaving group can offer TosMIC an efficient source of sulfonyl group, whereby it can act as a dual reagent and/or as a sulfonylation reagent. 12 In this regard, Bi et al introduced the dual role of TosMIC in a cascade reaction with propargylic alcohols, wherein TosMIC acted as a reagent for allenylative and sulfonylation in the presence of Ag 2 CO 3 to give (E)-vinyl sulfones (Scheme 1, eqn (1)). 14 Also, recently, our group investigated the behavior of TosMIC in treatment by 2-chloroquinoline-3-carbaldehydes, and the result was in tandem with the van Leusen/ring-closing procedure and tosylation to create 5-(2-tosylquinolin-3-yl)oxazoles, which testied to the dual-functional reactivity of mentioned isocyanide (Scheme 1, eqn ( 2)).…”

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

“…p -Toluenesulfonylmethyl isocyanide (TosMIC), a versatile synthon in organic chemistry, has been widely used to synthesize a myriad of valuable chemicals due to its high reactivity shown by the combination of acidic α-carbon atoms, isocyano groups, and sulfonyl moieties [ 18 ]. In general, TosMIC undergoes base-mediated 1,3-dipolar cycloadditions with activated alkenes to provide pyrroles as products [ 18 ] ( Scheme 1A ). Recently, alternative functionalizations using TosMIC as a tosyl source of arylalkenes or alkynes provided an attractive option for the synthesis of vinyl sulfones [ 19 – 23 ] ( Scheme 1B ).…”