The carbon–sulfur bond formation reaction is of paramount importance for functionalized materials design, as well as for biochemical applications. The use of expensive metal-based catalysts and the consequent contamination with trace metal impurities are challenging drawbacks of the existing methodologies. Here, we describe the first environmentally friendly metal-free photoredox pathway to the thiol–yne click reaction. Using Eosin Y as a cheap and readily available catalyst, C–S coupling products were obtained in high yields (up to 91%) and excellent selectivity (up to 60 : 1). A 3D-printed photoreactor was developed to create arrays of parallel reactions with temperature stabilization to improve the performance of the catalytic system.

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Visible light mediated metal-free thiol–yne click reaction

Arylsulfonyl compounds are among the most important compounds in pharmaceutical and medicinal chemistry. Hence, a wide variety of sulfonylation methods have been reported recently. This review summ...

Recent Advances in the Catalytic Synthesis of Arylsulfonyl Compounds

The 1,4-conjugate addition reaction between activated alkynes or acetylenic Michael acceptors and nucleophiles (i.e., the nucleophilic Michael reaction) is a historically useful organic transformation. Despite its general utility, the efficiency and outcomes can vary widely and are often closely dependent upon specific reaction conditions. Nevertheless, with improvements in reaction design, including catalyst development and an expansion of the substrate scope to feature more electrophilic alkynes, many examples now present with features that are congruent with Click chemistry. Although several nucleophilic species can participate in these conjugate additions, ubiquitous nucleophiles such as thiols, amines, and alcohols are commonly employed and, consequently, among the most well developed. For many years, these conjugate additions were largely relegated to organic chemistry, but in the last few decades their use has expanded into other spheres such as bioorganic chemistry and polymer chemistry. Within these fields, they have been particularly useful for bioconjugation reactions and step-growth polymerizations, respectively, due to their excellent efficiency, orthogonality, and ambient reactivity. The reaction is expected to feature in increasingly divergent application settings as it continues to emerge as a Click reaction.

Click Nucleophilic Conjugate Additions to Activated Alkynes: Exploring Thiol-yne, Amino-yne, and Hydroxyl-yne Reactions from (Bio)Organic to Polymer Chemistry.

One of the main goals of modern synthesis is to develop distinct reaction pathways from identical starting materials for the efficient synthesis of diverse compounds. Herein, we disclose the unique divergent reactivity of the combination sets of pyridinium salts and sulfinates to achieve sulfonative pyridylation of alkenes and direct C4-sulfonylation of pyridines by controlling the one- versus two-electron reaction manifolds for the selective formation of each product. Base-catalyzed cross-coupling between sulfinates and N-amidopyridinium salts led to the direct introduction of a sulfonyl group into the C4 position of pyridines. Remarkably, the reactivity of this set of compounds is completely altered upon exposure to visible light: electron donor–acceptor complexes of N-amidopyridinium salts and sulfinates are formed to enable access to sulfonyl radicals. In this catalyst-free radical pathway, both sulfonyl and pyridyl groups could be incorporated into alkenes via a three-component reaction, which provides facile access to a variety of β-pyridyl alkyl sulfones. These two reactions are orthogonal and complementary, achieving a broad substrate scope in a late-stage fashion under mild reaction conditions.

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Divergent reactivity of sulfinates with pyridinium salts based on one- versus two-electron pathways.

Emerging building blocks for medicinal chemistry: recent synthetic advances

A pericyclic approach for the synthesis of six-membered ring structures is described. The method employs 1,3-dienes with a 1-sulfur substituent in a tandem sequence of Diels–Alder and retro-ene reactions. In this pairing of [4 + 2] cycloaddition and 1,5-sigmatropic rearrangement, 1-sulfenyl-1,3-dienes engage in Diels–Alder reactions with electron-deficient dienophiles. Subsequently, the sulfenyl group of the cycloadducts is oxidized and unmasked to form allylic sulfinic acids, which undergo sterospecific reductive transposition via sulfur dioxide extrusion. The sequence can also include an inverse electron demand Diels–Alder reaction by using a 1-sulfonyl-1,3-diene. This combination of two pericyclic events offers novel stereocontrolled access to cyclohexenes that are inaccessible via a direct [4 + 2] cycloaddition route.

Tandem Diels-Alder and retro-ene reactions of 1-sulfenyl- and 1-sulfonyl-1,3-dienes as a traceless route to cyclohexenes.

An efficient protocol for the modular synthesis of sulfones and sulfonyl derivatives has been developed utilizing sodium tert-butyldimethylsilyloxymethanesulfinate (TBSOMS-Na) as a sulfoxylate (SO22−) equivalent. TBSOMS-Na, easily prepared from the commercial reagents Rongalite™ and TBSCl, serves as a potent nucleophile in S-alkylation and Cu-catalyzed S-arylation reactions with alkyl and aryl electrophiles. The sulfone products thus obtained can undergo the second bond formation at the sulfur center with various electrophiles without a separate unmasking step to afford sulfones and sulfonyl derivatives such as sulfonamides and sulfonyl fluorides.

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Silyloxymethanesulfinate as a sulfoxylate equivalent for the modular synthesis of sulfones and sulfonyl derivatives

A tandem approach for the stereoselective allylic reduction has been developed based on a strategy combining the palladium-catalyzed S-allylation and the sulfinyl retro-ene reactions. In a one-pot process employing various allylic carbonates, sodium t-butyldimethylsilyloxymethanesulfinate (TBSOMS-Na), easily prepared from the commercially available reagent Rongalite™, serves as a potent nucleophile to engage in the Tsuji–Trost S-allylation reaction generating allylic sulfone products. Subsequently, in situ deprotection of the TBSOMS group reveals allylic sulfinic acids which undergo stereospecific reductive transposition via sulfur dioxide extrusion to provide alkene products.

Jin Choi

Papers

Tandem Diels-Alder and retro-ene reactions of 1-sulfenyl- and 1-sulfonyl-1,3-dienes as a traceless route to cyclohexenes.

Silyloxymethanesulfinate as a sulfoxylate equivalent for the modular synthesis of sulfones and sulfonyl derivatives

Stereoselective allylic reduction via one-pot palladium-catalyzed allylic sulfonation and sulfinyl retro-ene reactions

Tandem Diels—Alder and Retro-Ene Reactions of 1-Sulfenyl- and 1-Sulfonyl-1,3-dienes as a Traceless Route to Cyclohexenes.