Unconventional Reactivity of Ethynylbenziodoxolone Reagents and Thiols: Scope and Mechanism

Abstract

1,2‐Dithio‐1‐alkenes are biologically active compounds widely implemented throughout organic synthesis, functional materials, coordination chemistry, and pharmaceuticals. Traditional methods for accessing 1,2‐dithio‐1‐alkenes often demand transition metal catalysts, specialized or air‐sensitive ligands, high temperatures, and disulfides (R2S2). Herein, a general and efficient strategy utilizing ethynylbenziodoxolone (EBX) reagents and thiols is presented that results in the formation of 1,2‐dithio‐1‐alkenes with excellent regioselectivity and stereoselectivity through unprecedented reactivity between the EBX and the thiol. This operationally simple procedure utilizes mild conditions, which result in a broad substrate scope and high functional‐group tolerance. The observed unexpected reactivity has been rationalized through both experimental results and DFT calculations.

Vinylbenziodoxol(on)es: Synthetic Methods and Applications

“…Few examples of vinylations with N‐ and O‐VBX were disclosed ( 12s and 12t ). The reaction of N‐ and S‐VBX with sulfur nucleophiles had been already reported previously by our group [62] and the Miyake group, [63] respectively (See Sect. 3.2 ).…”

“…Thiol nucleophiles were also used by the group of Miyake for the synthesis of 1,2-dithio-1-alkenes 72 (Scheme 36,A). [63] In presence of an excess of nucleo- phile and base, the addition of two thiol equivalents to the C�C triple bond of EBX 36 was observed, leading to (Z)-1,2-dithio-1-alkene 72 with loss of the hypervalent bond. A number of aliphatic and aromatic thiols, as well as thioglycosides are compatible with the reaction conditions.…”

Electrophilic Vinylation of Thiols under Mild and Transition Metal‐Free Conditions

“…The reaction was found to proceed under mild and transition metal‐free conditions, and contrary to the vinylation of nitrocyclohexane, regiospecific formation of ( E )‐1,2‐substituted vinyl sulfides was observed (Scheme d). During the course of our investigation, three types of metal‐free S‐vinylations with VBX were reported, although only 1–2 examples were given in each case: vinylation of sulfenate anions to ( E )‐alkenyl sulfoxides, thiophenol vinylation with a sulfonamide‐substituted VBX, and with a regular VBX using a large excess of thiophenol …”

“…Indeed, trisubstituted thioenamide 3 ah and thioenol ether 3 ai were obtained in excellent yields with good to complete Z‐selectivity . However, the corresponding disubstituted thioenamide 3 aj only formed in modest yield with 1,2‐bis(phenylthio)ethene as the main byproduct, and attempts to optimize the reaction conditions were in vain. Pleasingly, the corresponding Me 2 ‐substitued VBX reagent 2 p ( cf 2 e in Table ) proved more efficient, delivering thioenamide 3 aj in 59 % yield with complete Z‐selectivity and suppressed byproduct formation.…”

Preparation, Structure, and Reactivity of Pseudocyclic β‐Trifluorosulfonyloxy Vinylbenziodoxolone Derivatives

“…Recently, vinylbenziodoxolones 4 have attracted a significant research interest as potentially important reagents for electrophilic alkenylations [1p,2] . In particular, vinylbenziodoxolones have been used for vinylation of various substrates, such as vinylation of sulfur, [2a,b] oxygen, [2c] phosphine, [2d] or carbon atoms, [2e] and alkenylation reactions using metal reagents have been developed [2f–k] …”