Regio-, Diastereo-, and Enantioselective Decarboxylative Hydroaminoalkylation of Dienol Ethers Enabled by Dual Palladium/Photoredox Catalysis

Intermolecular photocatalytic hydroaminoalkylation (HAA) of alkenes have emerged as a powerful method for the construction of alkyl amines. Although there are some studies aiming at stereoselective photocatalytic HAA reactions, the alkenes are limited to electrophilic alkenes. Herein, we report a highly regio-, diastereo-, and enantioselective HAA of electron-rich dienol ethers and alpha-amino radicals derived from alpha-amino acids using a unified photoredox and palladium catalytic system. This decarboxylative 1,2-Markovnikov addition enables the construction of vicinal amino tertiary ethers with high levels of regio- (up to >19 : 1 rr), diastereo- (up to >19 : 1 dr), and enantioselectivity control (up to >99 % ee). Mechanistic studies support a reversible hydropalladation as a key step.

Automated summary

In this study, a highly efficient photoredox and palladium catalytic system was developed for the regio-, diastereo-, and enantioselective hydroaminoalkylation (HAA) of alkene substrates. The reaction, involving electron-rich dienol ethers and alpha-amino radicals derived from alpha-amino acids, enabled the construction of vicinal amino tertiary ethers with excellent regio-, diastereo-, and enantioselectivity control.