Iron-mediated site-selective oxidative C–H/C–H cross-coupling of aryl radicals with quinones: synthesis of β-secretase-1 inhibitor B and related arylated quinones

Abstract

Phenoxy radicals generated from substituted arenes were converted into para site selective C-aryl radicals and coupled with quinones, using an inexpensive FeCl₃–K₂S₂O₈ system, to obtain several arylated quinones, in good to moderate yields, under operationally simple and mild conditions. This method is useful for one pot synthesis of β-secretase-1 (BACE) inhibitor B. The arylated quinones were used as intermediates in the synthesis of phenothiazin-5-ones. Theoretical studies on the pharmacokinetic properties of phenothiazin-5-ones showed high lipophilicity (log p = 3.69), poor water solubility (log s = −6.42), and high gastrointestinal absorption (GI).