Active thionium species mediated functionalization at the 2α-position of indole derivatives

Abstract

A combination of dimethyl sulfoxide (DMSO) and trifluoroacetic anhydride (TFAA) mediates functionalization at the 2α-position of indole derivatives. Carbon and heteroatom nucleophiles were directly introduced via a one-pot procedure in excellent yields.

Alkylation Reactions with Alkylsulfonium Salts

“…In addition to methanol, other carbon- and heteroatom-nucleophiles 132 were also directly introduced into 131 to form 133 in excellent yields. 33` b c Similarly, a one-pot sulfonium-mediated synthesis of homo- and heterodimeric pyrroloindolines 140 was developed by combination of DMSO and Tf 2 O (Scheme 17b ). 33d Intramolecular cyclization of tryptamine with DMSO/Tf 2 O, followed by substitution with indoles or anilines, produced C3a-nitrogen-linked pyrroloindolines, including several bioactive alkaloids.…”

“…33 In 2011, Kawasaki and co-workers reported the sulfonium-mediated functionalization of indole derivatives 131 with methanol at the 2α-position in the presence of sulfoxide and trifluoroacetic anhydride (Scheme 17a ). 33` b c The active thionium species 134 were derived in situ from the alkyl or aryl sulfoxide and TFAA. In addition to methanol, other carbon- and heteroatom-nucleophiles 132 were also directly introduced into 131 to form 133 in excellent yields.…”

A Practical Regioselective Synthesis of Alkylthio- or Arylthioindoles without the Use of Smelly Compounds Such as Thiols

“…Furthermore, earlier approaches used reagents prepared from smelly compounds such as thiols, and thus are not conveniently prepared in laboratories and factories. We focused on using dimethyl sulfoxide (DMSO)-trifluoroacetic anhydride (TFAA) to introduce a strong electron withdrawing dimethylsulfonyl group, [23][24][25][26][27] to allow reliable electrophilic aromatic substitution into indoles that addresses the above problems. Furthermore, this reagent is a non-smelly MeS + synthon for methylthiolation and thus can replace smelly thiols or sulfides.…”

Cu-Catalyzed Oxidation of C2 and C3 Alkyl-Substituted Indole via Acyl Nitroso Reagents

“…As a result, syntheses of functionalized indoles have received a great deal of attention, although synthetic challenges remain. Successful synthetic approaches have included the C–H activation of the ring, construction of the indole core, functionalization via aerobic dearomatization and oxidative coupling reactions, among others. Nonetheless, these methods also come with limitations: direct C–H activation normally requires extra directing groups and specialized ligand/catalyst pairs, and strong oxidants and harsh conditions are needed for dearomatizations and oxidative coupling reactions.…”