Gold-catalyzed formal cycloadditions of alkynes for azaheterocycle syntheses

Abstract

In chapter 2, a novel and atom-economical synthesis of fully substituted 4-aminoimidazoles via gold-catalyzed selective [3+2] annulation of 1,2,4-oxadiazoles with ynamides is achieved. This protocol represents a new strategy to access α-imino gold carbenes, which corresponds to an unprecedented intermolecular transfer of N-acylimino nitrenes to ynamides. Moreover, the reaction proceeds with 100% atom economy, exhibits good functional group tolerance, and can be conducted in gram scale. Chapter 3 describes a novel, short, and flexible approach to diverse N-doped polycyclic aromatic hydrocarbons (PAHs) through gold-catalyzed π-extension of anthranils with o-ethynylbiaryls as reagents. This strategy uses easily accessible starting materials, is simple due to high step and atom economy, and shows good functionalgroup compatibility as well as scale-up potential. Mechanistically, the tandem reaction is proposed to involve a nucleophilic addition/ring opening/regiospecific C–H annulation/protodeauration sequence terminated by a Friedel-Crafts-type cyclization. Photophysical studies of the products indicated violetblue fluorescence emission with quantum yields up to 0.45. In chapter 4, a facile, site-selective and divergent approach to construct 2-aminopyrroles and quinoline-fused polyazaheterocycles is enabled by a simple gold(III) catalyst from ynamides and anthranils under mild reaction condition. This one-pot strategy uses readily available starting materials, proceeds in a highly stepand atom-economical manner, with broad substrate scope and scale-up potential. Notably, the key element of success in the present tandem reaction is a catalyst-directed preferable quenching of the in-situ generated gold carbene intermediates by a nucleophilic benzyl/2-furanylmethyl moiety on the ynamides as an alternative to the known C–H annulation leading to indoles. In chapter 5, a gold-catalyzed regioselective cyclocarboamination of ynamides with 1,3,5-triazinanes provides facile and modular access to valuable 5-aminotetrahydropyrimidines in good to excellent yields. It constitutes an unprecedented yet challenging annulation of ynamides with unstrained saturated heterocycles. This new protocol is distinguished by easy operation, readily available starting materials, stable four-atom building units, good functional-group compatibility and scaling-up potential. The preliminary mechanistic studies indicate that the present intermolecular cyclocarboamination arises from a pseudo-threecomponent [2+2+2] cycloaddition.