Photocatalyzed Decarboxylative Thiolation of Carboxylic Acids Enabled by Fluorinated Disulfide

Abstract

Thiolation of carboxylic acids using a disulfide reagent having tetrafluoropyridinyl groups is described. The light-mediated process is performed using an acridine-type photocatalyst. Primary, secondary, tertiary, and heteroatom-substituted carboxylic acids can be thiolated, and the method can be applied to the late-stage modification of a range of naturally occurring compounds and drugs. The fluorinated pyridine fragment is believed to enable the C−S bond formation. The resulting sulfides were used as redox-active radical precursors.

Preparation and Evaluation of Sterically Hindered Acridine Photocatalysts

“…Further, we evaluated the efficiency of obtained acridines as photocatalysts. For this purpose, we selected two reactions: decarboxylative thiolation (DT) recently reported by our group [11b] (Scheme 5, left) and copper‐catalyzed decarboxylative amination (DA) introduced by Larionov [10e] (Scheme 5, right). Turn over number (TON) [20] was utilized as a key performance parameter.…”

“…For nineteen acridines ( 2 a – f , h – p , s , t and A‐1 , A‐2 ) crystal structures were studied by X‐ray diffraction analysis. The crystal structure of acridine A‐3 was reported previously [11b] . These data allowed us to evaluate the steric effect on the C‐9 atom of acridines using the buried volume parameter V Bur , which reflects the portion of a sphere buried by overlap with the substituent [21] .…”

Decarboxylative Triazolation Enables Direct Construction of Triazoles from Carboxylic Acids

“…We hypothesized that such a tricomponent direct decarboxylative triazolation could be accomplished by a triple catalytic process that entails direct decarboxylative azidation and subsequent cycloaddition with alkynes. However, the combination of the two processes into one multicatalytic process is challenging because of the mismatch between the oxidatively mediated azidation and the oxidant-intolerant Cu I -catalyzed cycloaddition that is instead diverted to a Glaser-type alkyne dimerization. − Additionally, an efficient photocatalytic system would be needed that can both facilitate direct decarboxylation of difficult-to-oxidize carboxylic acids to bypass the typically required preactivation to more reactive carboxylic acid derivatives − and also be compatible with the organoazide- and triazole-forming catalytic cycles. Importantly, the successful development of direct, tricomponent conversion of carboxylic acids to triazoles necessitates a broad-scope, direct decarboxylative azidation of carboxylic acids that is tolerant to oxidation-sensitive processes and is mediated by a simple inorganic azide source.…”

Light-Promoted Dearylation of Perfluorinated Aryl Sulfides with N-Heterocyclic Carbene–Borane

“…Thus, after the thiolation was complete, the reaction mixtures were treated with either ammonium persulfate or alkyl bromides and then the final products were isolated. Starting sulfides 1 can be easily synthesized from various precursors: from alkenes via the thiol–ene reaction (for products 2a , 3a – 3c , 3h , and 4c – 4e ), via C–H activation of alkanes (for products 3d – 3g , 4a , and 4b ), via decarboxylative thiolation of carboxylic acids (for products 2c and 4f – 4i ), and even from menthol via the Mitsunobu reaction (for product 2b ), alkyl chloride ( 4j ), or thiol ( 4k ). The reaction tolerates ether ( 2c , 4e , 4f , and 4i ), nitrile ( 4j ), alcohol ( 3h ), and fluoroalkyl ( 4f ) groups.…”

“…Recently, we have introduced a perfluorinated pyridinylthio (PyfS) group as a convenient photoredox active fragment . The PyfS compounds ( 1 ) can be readily made from alkenes, alkanes, and carboxylic acids via light-mediated reactions (Scheme B). Under conditions of single-electron reduction, sulfides 1 undergo cleavage of the C­(sp 3 )–S bond generating the alkyl radicals (path a in Scheme C).…”