Site‐Selective Late‐Stage Aromatic [¹⁸F]Fluorination via Aryl Sulfonium Salts

Abstract

Angewandte Chemie Communications Scheme 2. Synthesis and fluorination of aryl sulfonium salts. TTO = thianthrene S-oxide;D BTO = dibenzothiophene S-oxide;B-DBTO = 3,7di-tert-butyldibenzothiophene S-oxide;M -DBTO = 2,8-dimethoxydibenzothiophene S-oxide. Angewandte Chemie Communications

Regio‐ and Stereoselective Thianthrenation of Olefins To Access Versatile Alkenyl Electrophiles

“…We have recently published a site‐selective aromatic C(sp 2 )−H functionalization reaction of in situ activated thianthrene‐ S ‐oxides with trifluoroacetic anhydride . The formed aryl thianthrenium salts were used as aryl electrophiles to form challenging bonds such as aryl C−SCF 3 , C−CF 3 , C−N, C−O, and C−F bonds. An extension of aromatic substitution chemistry to olefins is generally not successful because olefins typically react with electrophiles by addition.…”

Site-Selective Late-Stage C–H Functionalization via Thianthrenium Salts

“…The thianthrenation reaction works on electron-rich systems such as carbocyclic arenes, some heterocyclic arenes, and olefins. [10][11][12][13][14][15][16][17] Arenes can be as electron rich as di-methoxybenzene or as electron poor as chlorobenzene, although for such electron-poor arenes the fluorinated thianthrene reagent (TFT) is required. The reaction tolerates many functional groups, such as amides, amines, alcohols, ethers, esters, and nitrogen heterocycles, and allows functionalization of even complex small molecules, such as the natural product strychnine or the pharmaceutical dasatinib.…”

“…20 Dibenzothiophenium salts react with fluoride to give arylfluorides, most likely via the formation of a fluorosulfurane intermediate, 21 while thianthrenium salts preferentially undergo cleavage of the endocyclic C-S bonds under similar conditions. 11 By combining the dibenzothiophenation reaction with the nucleophilic substitution, a method for fluorination of arenes becomes possible (Scheme 10). The reaction conditions are very simple and do not depend on irradiation, as our previously described fluorination of thianthrenium salts under photoredox conditions so that it can be readily used for radiolabeling with 18 F.…”

Late-stage C–H thiolation via sulfonium salts using β-sulfinylesters as the versatile sulfur source

“…In addition, the selective cleavage of one of the three C-S bonds of aryl sulfonium salts via nucleophilic substitution were also realized to give aryl sul des (Scheme 1b). [36][37][38][39][40][41][42][43][44] While this strategy is promising, alkenyl, alkynyl, and alkyl sulfonium salts were not tolerated due to the fact that both of alkenyl and alkynyl sulfonium salts are good electrophilic Michael acceptors, [45][46][47][48][49] and alkenyl C(sp 2 )-S, C(sp)-S, and C(sp 3 )-S bonds of sulfonium salts are more prone to be attacked by nucleophiles than aryl C(sp 2 )-S bond. 36,50,51 Undoubtedly, the development of a general, practical, and TM-free C-H thiolation reaction for the construction of functionalized sul des, including aryl, alkenyl, alkynyl, and alkyl sul des, is highly desirable.…”