Iron-catalysed alkylation of 2-methyl and 4-methyl azaarenes with alcohols via C-H bond activation

The first Fe-catalysed alkylation of 2-methyl and 4-methyl-azaarenes with a series of alkyl and hetero-aryl alcohols is reported (>39 examples and up to 95% yield). Multi-functionalisation of pyrazines and synthesis of anti-malarial drug (+/-) Angustureine significantly broaden the scope of this methodology. Preliminary mechanistic investigation, deuterium labeling and kinetic experiments including trapping of the enamine intermediate1a ' are of special importance.