Study On Copper-Catalyzed Oxidation Reactions Using Oxime Esters As Substrates

The synthetic chemists always pursue to obtain useful compounds from easily available materials and through green and efficient transformation. Oxime compounds are easily obtained from the corresponding carbonyl compounds. The Beckmann rearrangement of oximes can form amides and the dehydration of aldehyde oximes generate nitriles. The radical and SN2-type reactions of oximes are important methods for the synthesis of nitrogen-heterocyclic compounds. With the development of transition-metal catalyzed coupling reaction, more and more reactions involving oximes have been reported. And a series of nitrogen compounds have been obtained through C-C and C-N bonds formation. However, the commonly used catalysts were noble-metals, such as palladium, rhodium, ruthenium. Compared to noble-metals, copper has many advantages such as inexpensiveness, low toxicity, stability, easy operation, and so on. Our group has been working on green oxidation with copper catalyst and found that the oxime compounds could be used as internal oxidants in many green and efficient transformation in presence of copper catalyst. In many cases, these reactions did not need external oxidants and have advantages of mild reaction conditions, good functional group tolerance and perfectly chemical selectivity. In this context, we summarized previous work about transformation of oximes and focused our works on copper-catalyzed reactions involving oxime esters. We have mainly utilized oxime esters as substrates and copper as catalyst to synthesize nitrogen-heterocyclic compounds via C-C, C-X and X-X bonds formation. A series of new results will be presented in the following six chapters:In chapter two, we researched a Cu-catalyzed [3+2]-type cyclization reaction of oxime esters and electron-deficient alkynes that provided a series of tri-and tetra-substituted pyrroles. The newly formed pyrroles were easily employed for further transformations to prepare pyrrolo[2,1-a]isoquinoline skeletons via ruthenium-catalyzed C-H bond activation and [4+2]-type cyclization reaction. Notably, pyrrolo[2,1-a]isoquinolines are indispensable structural motifs of lamellarin alkaloids.In chapter three, we reported a novel method for sulfone derivatives by copper-catalyzed oxidative coupling with oximes esters and sodium sulfinates. This transformation did not need external oxidants, ligands and bases, and proceed through N-O bond cleavage, activation of a C(sp3)-H bond and C-S bond formation under mild conditions. The oxime ester acted as both substrate and single oxidant.In chapter four, we researched copper-catalyzed cascade reaction of oxime esters, amines and paraformaldehyde for the synthesis of pyrroles. Detailed mechanistic studies showed that, this reaction consists of two tandem oxidation processes and the oxidants were different in the two oxidation processes. The first process was the formation of pyrazoline via coupling with oxime ester, amine and paraformaldehyde, the oxidant was oxime ester; and the subsequent process was the oxidative dehydrogenation of pyrazoline to produce pyrrole, the oxidant was oxygen.In chapter five, a new strategy for 2-aminothiazoles was developed via a copper-catalyzed coupling of oxime esters with isothiocyanates. Various 4-substituted and 4,5-disubstituted 2-aminothiazoles were formed smoothly under mild reaction conditions. This process involved copper-catalyzed N-O bond cleavage, activation of C(sp3)-H bond, and C-S/C-N bonds formations. It was noteworthy that the oxime esters were used not only as a substrate but also as a single oxidant. As far as we know, this was the first example for constructing thiazole ring via copper-catalyzed reaction involving oxime esters.In chapter six, a new strategy for thiazoles via copper-catalyzed cyclization reaction from oximes, anhydrides and potassiumthiocyanate(KSCN) was developed. The study revealed that potassium thiocyanate as sulfur source was very important for the reaction, when using sulfur or sodium sulfide, the reaction could not occurr. This reaction used easily available material and had good substrate suitability.In chapter seven, we described a method for 1H-indazoles via copper-catalyzed tandem reaction from 2’-bromoaryl oxime esters and amines. This transformation was triggered by an Ullmann-type reaction and followed by N-N bond formation. Various arylamines, alkylamines and sulfonamides could smoothly couple with 2’-bromoaryl oxime esters and various 1H-indazoles were formed in good to excellent yields under mild reaction conditions. The mechanism study showed that the oxime acetate group might act as ligand to promote the Ullmann-type reaction.