Synthesis of C2 Substituted Benzothiophenes via an Interrupted Pummerer/[3,3]‐Sigmatropic/1,2‐Migration Cascade of Benzothiophene S‐Oxides

Abstract

Functionalized benzothiophenes are important scaffolds found in molecules with wide ranging biological activity and in organic materials.W ed escribe an efficient, metal-free synthesis of C2 arylated, allylated, and propargylated benzothiophenes.T he reaction utilizes synthetically unexplored yet readily accessible benzothiophene S-oxides and phenols,a llyl-, or propargyl silanes in au nique cascade sequence.A ni nterrupted Pummerer reaction between benzothiophene S-oxides and the coupling partners yields sulfonium salts that lacka romaticity and therefore allowf acile [3,3]sigmatropic rearrangement. The subsequently generated benzothiophenium salts undergo ap reviously unexplored 1,2migration to access C2 functionalized benzothiophenes.

Synthesis of N‐Hydroxyindole Derivatives via Pd‐Catalyzed Electrophilic Cyclization

“…For the coupling of two nucleophilic (hetero)arenes, methods based on internal oxidants, i.e ., pre‐functionalization of substrates with oxidizing groups, may provide an enhanced level of selectivity over external‐oxidant‐based approaches (Scheme 1(a) vs. 1(b)). For example, Proctor and coworkers have utilized benzothiophene S‐ oxides that can function as an electrophilically modified thiophene for heterobiarylation 3a . or electrophilic activators of phenols for subsequent homo‐ and heterocoupling 3b,c …”

“…For example, Proctor and coworkers have utilized benzothiophene S‐ oxides that can function as an electrophilically modified thiophene for heterobiarylation 3a . or electrophilic activators of phenols for subsequent homo‐ and heterocoupling 3b,c …”

Alkylation Reactions with Alkylsulfonium Salts

“…Notably, C2-allylated and C2-propargylated benzothiophenes 165 were also synthesized by a cascade sequence involving interrupted Pummerer reaction of 3-substituted benzothiophene S -oxides 164 with 160 or 161 , [3,3]-sigmatropic rearrangement of the in situ formed allyl- or allenylsulfonium salts, and 1,2-migration of the 3,3-disubstituted benzothiophenium intermediates. 34h The facile [3,3]-sigmatropic rearrangement and 1,2-migration process ensured complete regioselectivity and tolerated a range of reactive functional groups in both coupling partners. Furthermore, Procter and co-workers reported a dual vicinal functionalization of electron-rich heteroarenes (e.g., 166 ) via an interrupted Pummerer cross-coupling of allyl or propargyl sulfoxides (e.g., 167 ) with subsequent charge-accelerated [3,3]-sigmatropic rearrangement of the corresponding sulfonium intermediates (e.g., 168 ), providing biologically relevant C3-sulfanylated and C2-allylated or -allenylated heterocycles (e.g., 169 ) under mild conditions.…”