Catalyst and base controlled site-selective sp2 and sp3 direct arylation of azine N-oxides

Site-selective direct arylation of both sp2 and sp3 sites on azine N-oxide substrates is described. The arylation reactions are carried out in either a divergent manner or a sequential manner. The sp3 arylation reaction is applied to the synthesis of the natural products, papaverine and crykonisine, and a rationale for low reactivity of electron-deficient aryl halides is provided. Mechanistic investigations point toward the intimate involvement of the base in the mechanism of these reactions.