The Nucleophilic Functionalization Of Azaarene Benzylic C-H Bonds

Pyridine and quinoline derivatives are the most common skeletons in naturalalkaloids and pharmaceutics with biological activity. As a result, the functionalizationof these azaarenes shows great significance in synthetic chemistry. Great progresseshave been made on these subjects, from the traditional synthetic methods totransition-metal-catalysis both in theoretic researches and applications. Among them,transition-metal-catalyzed benzylic C(sp3)-H bond functionalization of azaarenes andsubsequent C-C bond formation has attracted much attention because of efficiency,environmental benign and economy. There are many successful examples and somelimitations at the same time, such as: harsh reaction conditions; precious noble metalcatalysts, requiring derecting groups etc. Thus, we proposed a new method for thebenzylic C(sp3)-H bond functionalization of azaarenes by using the cheap, readilyavailable Br nsted acids as copper catalyst. This thesis focuses on the following twoaspects:(1). A practical Br nsted acid promoted benzylic C-H functionalization of2-methylazaarenes and nucleophilic addition to aldehydes was developed in good toexcellent yields. A six-membered hydrogen-bonding transition state is proposed to becrucial for the reaction. Readily availability of the two starting materials, the usage ofacetic acid as the catalyst and the facile reaction conditions will guarantee thissynthetic method attractive to the synthesis of bioactive pyridine and quinolinederivatives.(2). A copper/Br nsted acid dual-catalyst promoted oxidativecross-dehydrogenative-coupling of alkylazaarenes and tertiary amines forC(sp3)-C(sp3) bond formation was developed. This method uses dioxygen as theterminal oxidant under mild reaction conditions and would provide convenientbenzylic C-H transformation of alkylazaarenes to biological active pharmaceutics.