gamma-Regioselective Functionalization of 3-Alkenylindoles via 1,6- Addition to Extended Alkylideneindolenine Intermediates

Alkylideneindolenines are widely employed key electrophilic intermediates for the afunctionalization of the C-3 side chain of indoles. However, the reactivity of their extended (vinylogous) counterparts has not been carefully explored so far. These intermediates can undergo 1,4- or 1,6-addition with functionalization at alpha- or gamma position of the side chain, resulting in regioisomeric mixtures of products. This work demonstrates that a complete gamma-regioselectivity can be achieved in the reaction of 3-indol-3-yl allylic alcohols with various nucleophiles. This process is catalysed by just 1 mol% zinc(II) triflate at room temperature and entails the 1,6-selective addition of the nucleophile to an extended protonated alkylideneindolenine generated in situ. Indoles, pyrroles, anilines and thiols can be efficiently used as nucleophilic partners for this reaction, delivering the corresponding 3-vinyl substituted, g-functionalised indole products in moderate to good yields.