Methodological Study On The Construction Of C-O Bond And C-O Via C-H Activation With C(sp~2)-H

The C-C bond and C-O bond formations are very important in the domain of organic synthesis.The unmet demand in medicinal chemistry and organic chemistry for the synthesis of key organic compounds,such as active pharmaceutical ingredients,natural products,and special polymer materials,posed a necessity for the development of simple,efficient and practical synthetic methods.The traditional method of C-C bond and C-O bond formations require expensive metal catalysts,which will bring the hassles of tackling with metal residues in industrial applications,and a lot of byproducts always accompany the multi-step conversion progress.In pursuit of green chemistry and atom economy,the application of cheap available transition metal and even metal-free catalysis demonstrate a big advantage in C-C bond and C-O bond formations.The reported methods of C-C bond formation mainly include haloalkylation,Minisci reaction and direct construction of C-C bond by C-H bond activation.Comparing the other methods,the usage of C-H bond activation is a straightforward approach to form C-C bond with less steps.Furthermore,C-H activation usually occurs in friendly and feasible conditions,which make it available to synthesized difficult compounds that cannot be achieved by classical methods.The carbonyl group can be used in medicinal chemistry to increase drug lipophilicity and in organic chemistry to be converted to hydroxyl group.The introduction of carbonyl group through C-H activation provides a better choice for chemists and has attracted a lot of attention.The reported methods of C-O bond formation mainly include hydroxylation,carbonylation,etherification and esterification.The esterification by using classical synthetic blockers,such as formyloxy,acetoxy and propionyloxy groups plays a key role in medicinal chemistry and organic chemistry.In medicinal chemistry,the esterification is a strategy to increase drug's logP so as to improve drug absorption,metabolism and excretion properties.In organic chemistry,the esterification is the most frequently used strategy to introduce protective groups.Therefore,the construction of C-O bond through esterification has become a modern research hotspot.Some heteroaromatic groups,such as benzothiazole,quinolone,benzimidazole,pyrrolopyrimidine,pyridine,and pyrimidine,have drawn a lot of attentions form researchers,because of their frequent appearance in bioactive ingredients.The benzothiazole compound Methothiazide is used as pesticide for the control of gramineous weeds.The quinolone compound Quinine is used clinically for malaria.The benzimidazole compound astemizole is a marketed drug for the treatment of allergic rhinitis and chronic idiopathic urticarial,and the bis(heteroaryl)piperazine compound U87261 showed anti-HIV activity.Omeprazole is the first-line drug for the treatment of gastric ulcers.Quinoline is a common scaffold in chemical products which have been used in metallurgical industry,food industry,agriculture and pharmaceutical industry,so the development of novel quinolone-based bioactive compound will be of profound significance.Herein,two applications of C-H activation were introduced in detail.First,alkylation of benzoxazole compound through C-H activation can be more simple and efficient;second,ester group can be introduced to the 5-position of 8-amidequinoline compound selectively.