Copper-Mediated Synthesis of Indolequinones from Bromoquinones

Significance

Copper-mediated synthesis of indolequinones from corresponding bromoquinones and enamines is reported. The reaction was optimized in terms of oxidant (copper salts), base, and solvent. The reaction follows in the footsteps of Murphy [E. Comer, W. S. Murphy ARKIVOC, 2003, (vii), 286], who used catalytic amounts of CuBr₂ and air as terminal oxidant. This procedure proved finicky and very structure-dependant in the hands of Moody and colleagues. Substrate scope was well studied, and the yields range from modest to good. Noteworthy is the inferior reactivity of 2-bromo-5-methoxybenzoquinone (R^¹ = MeO, R^² = H; R^³ = R⁴ = R⁵ = Me, 49% yield) versus the 2-bromo-6-methoxybenzoquinone (89% yield). However, this is consistent with the findings of Murphy and with the proposed mechanism involving a 1,4-addition of the enamine and reoxidation. This was verified via the premature termination of the reaction to afford the intermediate uncyclized enaminoquinone.