Experimental and Computational Study on the Anti-Markovnikov Hydrofunctionalization of Olefins Using Glycine-Extended AQ-Auxiliaries

Two similar tridentate directing groups derived from glycine and 8-aminoquinoline were shown to enable the palladium-catalyzed anti-Markovnikov hydrofunctionalization of 4-pentenylamine with drastically different efficiencies. A computational investigation into the origin of the reactivity difference between these isomeric, carbonyl-transposed auxiliaries suggests that protonation state, thus charge of the substrate-metal complex prior to nucleopalladation is key. These investigations have culminated in a directing group design that can undergo Pd-catalyzed hydrofunctionalization under relatively mild conditions, as low as room temperature.

Automated summary

Two similar tridentate directing groups derived from glycine and 8-aminoquinoline showed significantly different efficiencies in the palladium-catalyzed anti-Markovnikov hydrofunctionalization of 4-pentenylamine. Computational investigation revealed that the protonation state and charge of the substrate-metal complex prior to nucleopalladation are crucial for the reactivity difference between these isomeric auxiliaries. These findings led to the design of a directing group that can undergo Pd-catalyzed hydrofunctionalization under relatively mild conditions, down to room temperature.