A Convenient Wittig‐Horner Mediated Synthesis of 3‐Vinylsulfide Derivatives of Indoles

Abstract

A simple and robust coupling protocol is reported to provide the previously unknown indole derivatives carrying vinylsulfide motifs attached to C−3 of the heterocycle. The developed strategy involved a Wittig‐Horner reaction with different phosphinoxide derivatives. The reaction conditions were optimized and its scope and limitations were assessed. The target compounds, including 3‐arylvinylsulfides as well as symmetric and dissymmetric bis‐vinylsulfides, were obtained in a straightforward way, as mixtures of geometric isomers, in good to excellent yields.

Synthesis and investigation of new indole‐containing vinyl sulfide derivatives: In silico and in vitro studies for potential therapeutic applications

“…Notably, extensive literature studies have emphasized the antioxidant properties of both synthetic and natural indole compounds [48] . This heightened activity can be primarily attributed to the presence of the highly electroreactive aromatic ring system [8–48] …”

“…Chemistry Typical procedure for the synthesis of the vinyl sulfides 3 a-e. [17] A stirred solution of the phosphine oxide (0.33 mmol) and the indole-3-carbaldehyde (0.44 mmol for 3 a-d, 0.83 mmol for 3 e) in THF (6 mL) was treated with NaH (60 % w/w in mineral oil, 1.2 mmol for 3 a-d, 1.32 mmol for 3 e). In the case of compounds 3 a-c and 3 e, HMPA (0.5 mL) was added for the reaction to proceed.…”

“…The series of vinyl sulfides derived from indole has been synthesized via a Wittig‐Horner reaction using indole‐3‐carbaldehydes 1 and sulfide‐containing phosphinoxide reagents 2 (Scheme 1), as previously described by our group [17] …”