Studies Of Nitrogen Directed C-H Activition

Carbon-hydrogen (C-H) bonds are ubiquitous in organic molecules. Utilization of such abundant chemical moieties as functional group equivalents could shorten route to synthetic targets. However, regio-and stereoselective functionalization of unactivated C-H bonds has remained one of the major challenges in organic chemistry. In order to control the regioselectivity, directing groups are usually introduced. In particular, nitrogen-and oxygen-bearing structural units have been extensively utilized for transition-metal catalyzed C-H cleavage.This dissertation mainly focused on the studies of nitrogen directed C-H bond activation, which include:1. Palladium(Ⅱ)-Catalyzed Direct Alkoxycarbonylation of Arenes with CO and AlcoholsAryl carboxylic esters are valuable commodity chemicals and useful synthetic building blocks for agrochemicals, active pharmaceutical ingredients. The traditional method to synthesis aryl carboxylic esters is Transition-metal-catalyzed carbonylation reactions involving the coupling of aryl halides (ArX) or arylmetallic compounds (ArM) with CO and various nucleophiles. We have developed an efficient protocol for the preparation of aryl carboxylic esters via palladium(Ⅱ)-catalyzed oxidative alkoxycarbonylation of arenes and heteroarenes with atmospheric pressure CO and alcohol. A variety of2-arylpyridine that incorporate electron-withdrawing and electron-donating groups, such as chloro and methoxy, were well tolerated.2. Pd(Ⅱ)-catalyzed oxidative alkoxycarbonylation of2-phenoxypyridine derivatives with CO and alcoholsPhenol derivatives are common and important structural motifs in bioactive natural products and pharmaceuticals. Many phenol derivatives, such as phenol esters, phenol carbamates, and2-phenoxypyridines, have been widely employed in C-H activation. We have achieved a Pd(Ⅱ)-catalyzed oxidative alkoxycarbonylation of phenol derivatives with atmospheric pressure of CO-O2and alcohols. Primary alcohols, such as MeOH and EtOH, gave moderate yields. Notably, secondary alcohols, such as isopropanol, were also compatible with this protocol. When CF3CH2OH and phenol were used, the ortho-alkoxycarbonylated products were hydrolyzed to phenols under the standard reaction conditions. Furthermore, we demonstrate the utility of this protocol in the derivatization of a natural product, which showcases that this reaction could be applied in late stage total synthesis.3. Palladium-Catalyzed Oxidative Olefination of Phenols Bearing Removable Directing Groups under Molecular Oxygen.Transition-metal-catalyzed oxidative cross-coupling reactions have emerged as powerful tools for the construction of new C-C and C-heteroatom bonds in terms of atom and step economy. A number of oxidants such as inorganic salts, have been widely employed in these transformations. We have developed a simple and efficient palladium-catalyzed direct C-H olefination of phenol derivatives with a readily removable directing group. This protocol can proceed well with oxygen at atmospheric pressure as the sole oxidant without the need of any other additives, providing an expeditious strategy for the synthesis of o-alkenyl or o-alkyl phenols.4. Rh(Ⅲ)-Catalyzed Cascade Oxidative Annulation of Aryl Ketoximes with Diphenylacetylene by Sequential Cleavage of Multiple C-H BondsPolycyclic aromatic and heteroaromatic hydrocarbons are an important class of compounds in material science. The traditional methods for the construction of these polycyclic aromatic are typically limited by the availability of the starting materials and multistep procedures. Moreover, the construction of more densely arylated arenes still poses a significant challenge, since the cross-coupling reactions are usually sensitive to steric hindrance. we have demonstrated a rhodium(Ⅲ)-catalyzed cascade oxidative annulation reactions of aryl/heteroaryl ketoximes with alkynes using Cu(OAc)2as an oxidant, generating highly congested Polycyclic aromatic and heteroaromatic hydrocarbons in good yields. This reaction protocol features with short reaction time, high compatibility with various functional groups and high yields.