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

Abstract

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. 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.

Vinylbenziodoxol(on)es: Synthetic Methods and Applications

“…2.2). [61] Nucleophilic addition onto O-VBX reagents 44 was studied by our group. Surprisingly, the O-VBXs 44 displayed an oxy-allyl cation-like behavior, rather than the expected vinyl cation reactivity (Scheme 37).…”

“…Phenyl‐VBX ( 2a ) could also be transformed to vinyl sulfides under the reported conditions, which is consistent with the work later published by the group of Olofsson on electrophilic vinylation of thiols with VBX (see Sect. 2.2 ) [61] …”

“…The same group applied VBX reagents to the electrophilic alkenylation of thiols under mild and transition metal‐free conditions ( Scheme 5). [61] After screening of several bases and solvents, t BuOK in THF was selected, allowing the formation of products 12 in good yield, excellent trans stereoselectivity and with minor formation of disulfide side products. The reaction was suitable for a large array of thiols, including aromatic ( 12a – 12i ) and aliphatic thiols (primary ( 12j ), secondary ( 12k ) and tertiary ( 12l )).…”

Structure-reactivity analysis of novel hypervalent iodine reagents in S-vinylation of thiols

“…(Figure 1A), (Stridfeldt et al, 2016;Declas et al, 2020). Transition metal-free applications include S-and P-vinylation methodologies, (Castoldi et al, 2020a;Castoldi et al, 2020b;Di Tommaso et al, 2022), as well as photocatalytic C-vinylations with redox active compounds (Pal et al, 2023) and others. (Davies et al, 2017;Le Vaillant et al, 2018;Liu et al, 2018;Jiang and Studer, 2019;Li et al, 2019;Liu et al, 2020).…”

“…(Fernández González et al, 2013;Shimbo et al, 2019). While we evaluated the influence of core-substituents on VBX in the S-vinylation of thiols, (Castoldi et al, 2020b), there are no broad studies investigating the structural and electronic effects of varying these groups on vinylating reagents. (Mironova et al, 2023).…”