Conjugate addition-enantioselective protonation to forge tertiary stereocentres α to azaarenes via cooperative hydrogen atom transfer and chiral hydrogen-bonding catalysis

Cooperative hydrogen atom transfer and chiral hydrogen-bonding catalysis as a new platform for the asymmetric synthesis of azaarene derivatives is reported. By using a tetrabutylammonium decatungstate as the photocatalyst and a chiral phosphoric acid as the hydrogen-bonding catalyst, transformations of a variety of commercially available hydrocarbons and silanes with diverse alpha-branched 2-vinylazaarenes could efficiently experience a tandem radical conjugate addition and enantioselective protonation process, providing a convenient and fully atom economical approach to access a range of valuable enantioenriched alpha-tertiary azaarenes in high yields with good to excellent enantioselectivities (up to 93% ee). Through the direct use of tert-butyl methylcarbamate as the feedstock, this method enables a highly practical and concise synthesis of the enantiomerically pure medicinal molecule pheniramine (Avil). (c) 2022, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Automated summary

This study presents a new platform for the asymmetric synthesis of azaarene derivatives through cooperative hydrogen atom transfer and chiral hydrogen-bonding catalysis. By using a photocatalyst and a hydrogen-bonding catalyst, commercially available hydrocarbons and silanes can efficiently undergo transformations with 2-vinylazaarenes, leading to valuable enantioenriched alpha-tertiary azaarenes with high yields and good to excellent enantioselectivities.