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Transition‐Metal‐Free Reductive Hydroxymethylation of Isoquinolines
Author(s) -
Reeves Benjamin M.,
Hepburn Hamish B.,
Grozavu Alexandru,
LindsayScott Peter J.,
Donohoe Timothy J.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201908857
Subject(s) - chemistry , isoquinoline , tandem , transition metal , combinatorial chemistry , deuterium , reductive elimination , organic chemistry , catalysis , materials science , physics , quantum mechanics , composite material
A transition‐metal‐free reductive hydroxymethylation reaction has been developed, enabling the preparation of tetrahydroisoquinolines bearing C4‐quaternary centers from the corresponding isoquinolines. Deuterium labelling studies and control experiments enable a potential mechanism to be elucidated which features a key Cannizzaro‐type reduction followed by an Evans–Tishchenko reaction. When isoquinolines featuring a proton at the 4‐position are used, a tandem methylation‐hydroxymethylation occurs, leading to the formation of 2 new C−C bonds in one pot.