Remote Hydroamination of Disubstituted Alkenes by a Combination of Isomerization and Regioselective N-H Addition

Remote hydrofunctionalizations of alkenes incorporate functional groups distal to existing carbon-carbon double bonds. While remote carbonylations are well-known, remote hydrofunctionalizations are most common for addition of relatively nonpolar B-H, Si-H, and C-H bonds with alkenes. We report a system for the remote hydroamination of disubstituted alkenes to functionalize an alkyl chain selectively at the subterminal, unactivated, methylene position. Critical to the high regioselectivity and reaction rates are the electronic properties of the substituent on the amine and the development of the ligand DIP-Ad-SEGPHOS by evaluating the steric and electronic effects of ligand modules on reactivity and selectivity. The remote hydroamination is compatible with a broad scope of alkenes and aminopyridines and enables the regioconvergent synthesis of amines from an isomeric mixture of alkenes. The products can be derivatized by nucleophilic aromatic substitution on the amino substituent with a variety of nucleophiles.

Automated summary

Remote hydrofunctionalizations of alkenes enable the incorporation of functional groups distal to carbon-carbon double bonds. This study presents a system for the remote hydroamination of disubstituted alkenes, selectively functionalizing the subterminal, unactivated, methylene position of an alkyl chain. The high regioselectivity and reaction rates are attributed to the electronic properties of the amine substituent and the ligand DIP-Ad-SEGPHOS, which was developed by considering the steric and electronic effects of ligand modules. The remote hydroamination is compatible with a diverse range of alkenes and aminopyridines, allowing for the regioconvergent synthesis of amines from isomeric mixtures of alkenes. The resulting products can be further modified through nucleophilic aromatic substitution reactions.