Studies Of Chelation-assisted Catalytic C-H Bond Functionalization

The transition-metal catalyzed functionalization of C-H bonds has exerted a huge impact on the bond-disconnection strategies for complex molecules through a direct and step-economical manner. Particularly, chelation-assisted C-H bond activation has attracted increasing attentions and significant advances have been achieved, providing novelty avenues for the synthesis of valuable organic motifs. However, compared with the functionalization of sp2 C-H bonds, the development of catalytic methods for activating sp3 C-H bonds is still in its early stage. On the other hand, with the increasing interest in sustainable catalysis, considerable effort in this area has been directed toward the new reactions by utilizing low cost and environmentally benign first-row transition metals in the place of noble transition metals currently. This dissertation mainly focused on the transition metal-catalyzed chelation-assisted C-H bonds functionalization. The contents were listed as follows:1. Copper-mediated aryloxylation and vinyloxylation of β-C(sp)-H bond of propionamides with organosilanesAryl-alkyl ethers serve as useful intermediates in organic synthesis and are found in an impressive number of biologically relevant molecules and natural products. Although the Ullmann aryl-alkyl ether synthesis has been widely used, the method requires preactivation of substrates and often suffers from harsh reaction conditions.We investigated a novle copper-mediated aryloxylation/vinyloxylation of the C(sp3)-H bond with organosiloxane reagents through a sequential oxidation and arylation/vinylation process with the assistance of an 8-aminoquinolyl auxiliary. This reaction pattern allows the efficient synthesis of aryl-alkyl ethers from readily available starting materials and provides a new avenue for direct C-H bond functionalizations. The preliminary studies on the reaction mechanism indicate that Cu(OAc)2 performs as both the promoter and the source of oxygen.2. Cobalt-catalyzed cyclization of aliphatic amides and terminal alkynes with silver-cocatalystCobalt catalysts in various oxidation states have attracted particular attention due to their unique properties demonstrated in C(sp2)-H activation as new catalytic systems. In contrast to the direct functionalization of sp2 C-H bond, the use of cobalt catalysts in the transformations of unactivated sp3 C-H bond cleavage is extremely underdeveloped. We discovered a new method of cobalt-catalyzed synthesis of pyrrolidinones from aliphatic amides and terminal alkynes through a C-H bond functionalization process on unactivated sp3 carbons with the silver cocatalyst using a bidentate auxiliary. For the first time, a broad range of easily accessible alkynes are exploited as the reaction partner in C(sp3)-H bond activation to give the important 5-ethylidene-pyrrolidin-2-ones in a site-selective fashion. This new transformation demonstrates good functional group tolerance, excellent reactivity, and high yields. MALDI-TOF analysis and related experiments evidence that the coordination of both ligand and solvent toward cobalt serve as critical factors for ensuring reactivity of this sp3 C-H functionalization reaction. This cobalt catalytic system can be successfully extended to the aromatic amides and thus diverse isoindolinones can be accessed.3. Copper(Ⅱ)/silver(Ⅰ)-catalyzed sequential alkynylation and annulation of aliphatic amides with alkynyl carboxylic acids:Efficient synthesis of pyrrolidonesCatalytic decarboxylative coupling is considered as one of the most promising atom-economical organic processes for C-C bond formation because the use of a stoichiometric amount of organometallic or organic halide reagents can be avoided. In recent years, the development of new decarboxylation reactions capable of catalytically transforming the inert C(sp2)-H bonds of organic molecules into useful functional groups opens up attractive new strategies for C-C bond formation, which has rapidly emerged as a very active area of research. However, the catalytic decarboxylative coupling reaction by using an unactivated alkyl C-H bond as the reaction partner has not yet been achieved. We have developed a highly efficient method for the synthesis of pyrrolidones via the copper-catalyzed tandem decarboxylative cross-coupling/cyclization of aliphatic amides and alkynyl carboxylic acids. For the first time, the catalytic decarboxylative process is extended to the direct fuctionalization of unactivated sp3 C-H bond. A broad range of easily accessible alkynyl carboxylic acids were introduced at the P-methyl group of aliphatic amides with the assistance of an 8-aminoquinolyl auxiliary group via decarboxylation to achieve the subsequent cyclic C-N bond formation within one hour and high selectivity of P-methyl groups over methylene groups was observed. The reaction features short reaction time (1 h), a broad substrate scope, and readily available reagents.4. Rhodium(Ⅲ)-catalyzed one-pot access to isoquinolines and heterocycle-fused pyridines in aqueous medium via C-H cleavageEfficient synthesis of heterocycles, especially nitrogen-containing heterocyclic compounds, has been an important goal of synthetic organic chemists. In particular, isoquinolines and pyridines as important structural motifs are ubiquitous in natural products and pharmaceuticals, and they can perform as ligands in transition-metal catalyzed transformations as well. Thus, efficient synthesis of these heterocyclic scaffolds has attracted extensive attention. We developed an efficient and practical access to isoquinolines and heterocycle-fused pyridines by Rh(III)-catalysis. A broad scope of aryl ketones and alkynes participated in the reaction to afford corresponding heterocycles. Importantly, molecular oxygen was exploited as the sole oxidant in the reaction by producing water as the only co-product. Moreover, easily available NH4OAc is utilized as "N" source, which makes the method quite practical and low-cost. It is interesting that the reaction proceeds efficiently in aqueous medium to give the desired products in mediate to excellent yields.5. Rhodium(III) catalyzed C(sp2)-H bond functionalization in aqueous medium using O2 as the sole oxidant:a facile synthesis of isocoumarinsThe development of sustainable reaction medium is an important goal in contemporary organic synthesis. Water performing as a solvent has aroused considerable interest in the field of organic synthesis due to its green nature, such as cheap, readily available, non-toxic and non-polluting. We disclosed Rh(III)-catalyzed efficient and practical access to isocoumarin derivatives by oxidative annulation of benzoic acids with alkynes in aqueous medium. The protocol features readily available starting materials, simple and mild reaction conditions, and tolerates a wide range of functional groups. Notably, this catalytic system was also able to be applied to the synthesis of phthalides from benzoic acid and alkenes.