Copper And Cobalt Catalyzed C(sp~2)-H Bond Alkoxylation And Alkynylation

In this dissertation, the cheap-transition-metal catalyzed C-H bond functionalizations assisted by 2-aminopyridine 1-oxide directing group have been studied. The main contents are as follows:1. Copper-mediated direct alkoxylation of C(sp2)-H bondThe copper-mediated direct C(sp2)-H bond alkoxylation methodology has been developed, assisted by an N,O-bidentate directing group(Scheme 1). The direct dehydrogenative cross-coupling of arylamides installing 2-aminopyridine 1-oxide moiety with alcohols delivered the alkoxylated product using stoichiometric copper(I) chloride under an air atmosphere. A series of control experiments have been conducted to discuss the putative reaction mechanism, indicating that the reaction underwent a pincer “Cu(III)-OR” intermediacy. The mechanism revealed the influence of oxygen in the air on the reaction. It is worth mentioning that the reaction system shows remarkable compatibility when hexafluoroisopropanol is used as a coupling partner. Various functional groups including methyl, methoxyl, trifluoromethyl, sulfonyl, ester, nitro and halogen at different positions of the arenes were well tolerated. The reaction was proved to be an effective protocol to synthesize a series of hexafluoroisopropoxylated compounds in excellent yields and chemoselectivity. The directing group can be easily removed by base hydrolysis, affording o-alkoxylated benzoic acids.2. Cobalt-catalyzed direct alkoxylation of C(sp2)-H bondwe have developed the first cobalt-catalyzed alkoxylation of arylamides(Scheme 2). Benzamide substrates bearing a variety of functional groups could smoothly undergo the coupling reaction with alcohols, achieving the corresponding alkoxylated products in moderate to good yields. The protocol featured the low-cost catalyst, mild reaction conditions, easy to handle nature. Moreover, this reaction is the first example of the direct alkoxylation of olefinic carboxamides through C-H bond activation. The control experiments including radical quencher, kinetic studies and DFT calculations, suggested that the reaction process proceeded via an intermolecular single-electron-transfer(SET) pathway.3. Cobalt-catalyzed alkynylation/annulation of C(sp2)-H bondwe have disclosed the first cobalt-catalyzed tandem alkynylation/annulation of C(sp2)-H bond with terminal alkynes(Scheme 3). The dehydrogenative cross-coupling of arylamides and terminal alkynes could yield the 3-methyleneisoindolin-1-ones in one step using cobalt(II)oxalateantetrahydrate as the catalyst through the use of an N,O-bidentate directing group. This reaction protocol was attractive owing to the broad substrates, the relative mild reaction conditions and easy to handle nature. Moreover, the catalyst was rather cheap and the loading of cobalt salts could reduced as low as 5 mol%. In the transformation, silver(I) acetate was proved to serve as the terminal oxidant. The oxadiazine salt can be synthesized in one step from the annulation product, and the directing group could be removed and in three steps, delivering the 3-benzylideneisoindolin-1-one. A series of control experiments have been conducted to clarify that the reaction underwent a pincer “cobalt(III)-acetylide” intermediacy.