Sustainable radical approaches for cross electrophile coupling to synthesize trifluoromethyl- and allyl-substituted tert-alcohols

Trifluoromethylated molecules have gained privileged recognition among the medicinal and pharmaceutical chemists. Sustainable photoredox- and electrochemical processes were employed to facilitate the relatively less explored radical cross-electrophile coupling to access trifluoromethyl- and allyl-substituted tert-alcohols. Reactions proceed through trifluoromethyl ketyl radical and allyl radical intermediates, which undergo challenging radical-radical cross-coupling. The developed transformations are mild and chemo-selective to give cross-coupled products and deliver a wide range of valuable trifluoromethyland allyl-containing tertiary alcohols. Both processes can also be applied for the synthesis of amine variant containing trifluoromethyl and allyl moiety, which is considered as amide bioisostere.

Automated summary

Trifluoromethylated molecules have gained privileged recognition among medicinal and pharmaceutical chemists. Sustainable photoredox- and electrochemical processes were employed to access trifluoromethyl- and allyl-substituted tert-alcohols through radical cross-electrophile coupling, providing valuable tertiary alcohols with trifluoromethyl and allyl groups. The transformations are mild and chemo-selective, with potential applications in the synthesis of amine variants as amide bioisosteres.