Photochemical 1,3-boronate rearrangement enables three-component N-alkylation for α-tertiary hydroxybenzylamine synthesis.

ABSTRACT: Hydroxybenzylamines are prevalent in drugs and bioactive molecules, including various antimalarial and anticancer drugs. α-tertiary alkylation of amines impacts drug-target interactions significantly through their influence on basicity and lipophilicity. Traditional N-alkylation methods, especially for α-tertiary amines, suffer from limitations due to high energy barriers from steric hindrance. In this work, we leverage visible light irradiation to enable the organoboronic acid addition to sterically hindered ketimines in the excited state. Notably, it overcomes the limitations of the well-explored Petasis reaction, which is restricted to aldimines due to the high energy barrier associated with ketimines (51.3 kcal/mol). This three-component coupling of aliphatic amines, o-phenolic ketones

SUBMITTER: Zou P 

PROVIDER: S-EPMC11599903 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature