Thioorthoesters in the activated Pictet–Spengler cyclization. Synthesis of 1-thiosubstituted tetrahydroisoquinolines and carboncarbon bond formation via sulfonyl iminium ions generated from N,S-sulfonyl acetals

1-Substituted β-Carbolines by a Pictet−Spengler Cyclization with Thioortho Esters and Carbon−Carbon Bond Formation via N-Sulfonyl Iminium Ions Generated from N,S-Sulfonyl Acetals

“…This reaction outcome can be ascribed to the better charge stabilization ability of the phenylthio moieties in relation to their alkylthio congeners. Interestingly enough, the Hevesi group has previously noted a similar behavior between these organochalcogen derivatives while working with methyl- and phenyl-selenoesters,7a and in a recent study we reported a similar but more evident trend when alkyl- and arylthioortho esters were reacted with β-phenethylamines to produce 1-thiosubstituted tetrahydroisoquinolines . Interestingly, however, it was not possible to obtain any cyclized product when a highly hindered thioorthoformate such as tris( tert -butylthio)methane was employed as the masked carbonyl component (entry 8).…”

“…7 Recently, we disclosed the use of thioortho esters as electrophilic partners in the Pictet-Spengler reaction of N-sulfonyl-β-phenethylamines affording 1-heterosubstituted tetrahydroisoquinolines. 8 This strategy improved the scope of the Pictet-Spengler cyclization, giving access to a new family of compounds, some of them otherwise difficult to obtain.…”

“…The required thioortho esters were conveniently prepared in high yields by the BF 3 ‚Et 2 O-catalyzed reaction of (EtO) 3 CH or (MeO) 3 CH with the corresponding mercaptans. 8,9 Initial attention was focused on the use of tris(phenylthio)methane as an electrophile, employing its cyclocondensation with N-tosyltryptamine as a model reaction, leading to compound 3a. The transformation was next explored using ZnBr 2 , TiCl 4 , and SnCl 4 as Lewis acids and different solvent systems (CH 2 Cl 2 , CH 3 CN, CH 3 CN/CH 2 Cl 2 , ClCH 2 CH 2 Cl).…”

“…Interestingly enough, the Hevesi group has previously noted a similar behavior between these organochalcogen derivatives while working with methyl-and phenyl-selenoesters, 7a and in a recent study we reported a similar but more evident trend when alkyl-and arylthioortho esters were reacted with β-phenethylamines to produce 1-thiosubstituted tetrahydroisoquinolines. 8 Interestingly, however, it was not possible to obtain any cyclized product when a highly hindered thioorthoformate such as tris(tert-butylthio)methane was employed as the masked carbonyl component (entry 8). By use of the optically active N-tosyltryptophan (entry 9), we examined the possibility of 1,3-chirality transfer within this system.…”

“…The required thioortho esters were conveniently prepared in high yields by the BF 3 ·Et 2 O-catalyzed reaction of (EtO) 3 CH or (MeO) 3 CH with the corresponding mercaptans. , …”