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Transition-Metal-Free Reductive Hydroxymethylation of Isoquinolines.

ABSTRACT: 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.

SUBMITTER: Reeves BM

PROVIDER: S-EPMC6856840 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Transition-Metal-Free Reductive Hydroxymethylation of Isoquinolines.

Reeves Benjamin M BM Hepburn Hamish B HB Grozavu Alexandru A Lindsay-Scott Peter J PJ Donohoe Timothy J TJ

Angewandte Chemie (International ed. in English) 20190924 44

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 occur ...[more]

PMID: 31486205

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