Author: Prasenjit Bera & Dr. Koomkoom Khawas
DOI Link: https://doi.org/10.70798/Bijmrd/04090005
Abstract: Nucleophilic aromatic substitution (SNAr) is a powerful platform for constructing arylheteroatom bonds without obligatory transition-metal catalysis. Among the available nucleophiles, sulfurcentered reagents are particularly attractive because sulfur combines high polarizability with substantial nucleophilicity and can therefore engage efficiently with activated aryl and heteroaryl electrophiles. This review-style manuscript examines sulfur-nucleophile-mediated SNAr as a complementary strategy for C–S bond construction, with emphasis on mechanistic requirements, substrate electronics, leaving-group effects, solvent and base effects, sulfur-nucleophile scope, polyfluoroarene substitution, heteroaryl SNAr, sequential substitution, and reversible sulfur exchange. Recent literature demonstrates that activated aryl fluorides, chlorides, and bromides can undergo metal-free substitution with thiophenols and selected alkyl thiols under basic conditions, while electron-deficient heteroaryl halides can react with thiols under similarly practical conditions. Polyfluoroarenes provide an additional class of highly electrophilic substrates in which the fluorination pattern controls regioselectivity. More unusual reversible sulfur-exchange processes further demonstrate that SNAr can operate as a dynamic rather than strictly irreversible transformation. The literature is evaluated here with particular attention to its relevance to sulfur-containing synthetic systems and to the prospective functionalization of 3-sulfonyl phthalide-related frameworks. Importantly, the literature surveyed does not establish conventional sulfur-nucleophile SNAr of 3-sulfonylphthalides themselves. Accordingly, direct reactions involving 3-sulfonylphthalides are treated as prospective design hypotheses rather than reported precedents. This distinction preserves a clear boundary between established chemistry and future synthetic opportunities while identifying experimentally testable directions for C–S bond construction, annulation, rearrangement, and sulfur-centered diversification.
Keywords: Nucleophilic Aromatic Substitution; SNAr; Sulfur Nucleophile; Thiophenol; Thiolate; C–S Bond Formation; Polyfluoroarene; Heteroaryl Halide; Sulfur Exchange; 3-Sulfonylphthalide.
Page No: 47-58