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

Laura Castoldi,Berit Olofsson,Marcus Reitti,Ester Maria Di Tommaso,Barbara Gräfen

doi:10.1002/ange.202002936

Abstract

AbstractThe iodine(III) reagents vinylbenziodoxolones (VBX) were employed to vinylate a series of aliphatic and aromatic thiols, providing E‐alkenyl sulfides with complete chemo‐ and regioselectivity, as well as excellent stereoselectivity. The methodology displays high functional group tolerance and proceeds under mild and transition metal‐free conditions without the need for excess substrate or reagents. Mercaptothiazoles could be vinylated under modified conditions, resulting in opposite stereoselectivity compared to previous reactions with vinyliodonium salts. Novel VBX reagents with substituted benziodoxolone cores were prepared, and improved reactivity was discovered with a dimethyl‐substituted core.

Highlights

The iodine(III) reagents vinylbenziodoxolones (VBX) were employed to vinylate a series of aliphatic and aromatic thiols, providing E-alkenyl sulfides with complete chemo- and regioselectivity, as well as excellent stereoselectivity
Intrigued by the different regiochemical outcome with VBX and vinyliodonium salts (Scheme 1 b), and inspired by Wasers EBX-alkynylation of thiols,[20] we have investigated the reactivity of VBX with thiols, and report our
Waser and co-workers recently reported a vinylation of thiophenol with a Z-configured sulfonamide-substituted VBX to provide a thioenamide with moderate Z-selectivity.[10d]. Considering the excellent stereoselectivity of our methodology, we were intrigued to investigate the reactivity of such reagents under our conditions

Summary

Toluene TMG

[a] Reaction conditions: 1 a (0.3 mmol) and base were stirred in solvent for 5 min before addition of 2 a. [b] 1H NMR yield using trimethoxybenzene as internal standard. [c] Addition of VBX, base. [d] Anhydrous and degassed solvent. [e] PhS-TMS (7) and TBAF (1.0 equiv) used instead of 1 a and base. Waser and co-workers recently reported a vinylation of thiophenol with a Z-configured sulfonamide-substituted VBX to provide a thioenamide with moderate Z-selectivity.[10d] Considering the excellent stereoselectivity of our methodology, we were intrigued to investigate the reactivity of such reagents under our conditions. Ochiai and co-workers have demonstrated that metal-free vinylation of various nucleophiles with E-alkylvinyl(phenyl)iodonium salts result in Z-vinylated products through a vinylic SN2 mechanism.[3a] In this fashion, vinylation of mercaptobenzothiazole in the absence of base resulted in selective formation of the corresponding Z-vinylsulfide.[3a] To compare the reactivity of VBX with vinyliodonium salts, the vinylation of a small series of mercaptothiazoles 8 (X = S) was investigated This substrate class could be vinylated in moderate yields and high stereoselectivity (E/Z 10:1 to 20:1) under modified reaction conditions (Scheme 4).[21] Interestingly, we observed opposite stereochemistry compared to previous results with the vinyliodonium salt.

Conflict of interest

Experimental Section