Study On C-O And C-C Bonds Formation With Diazoester:Using Acid Surface Modified Sewage Sludge Or Small Molecule Acid As Catalyst

Diazoester is an organic synthesis intermediate that has found widespread application,and it readily forms more reactive carbene intermediates under various conditions such as transition-metal catalysis,small molecule acid catalysis,or exposure to light or heat.Diazoester is involved in a variety of reaction pathways,including X-H insertion reactions（where X=O,C,S,N,B,Si,etc.）,C-C coupling reactions,olefin cyclopropanation,and ylide formation.Among these reactions,O/C-H insertion and C-C coupling reactions are common methonds to form C-O/C bonds.Sewage sludge is a significant by-product generated during wastewater treatment,which is widely distributed,low-cost and easily accessible.So far,it is not only used as fertilizer,but also as an adsorbent or for the degradation of organic wastewater.This work,we use surface modified sewage sludge and small molecule acid as catalysts,successfully realizing the O-H insertion and C-C coupling reactions of diazo esters.The above catalysts may provide more effective green methods for the synthesis of the skeleton structures for phenoxyacetate or diarylacetate drugs and bioactive compounds,which is very innovative.Based on the above contents,we have also successfully developed a small molecule acid catalytic system,which avoids the surface modification of sludge by acids,directly applies acids to the homogeneous O-H and S-H insertion reactions of diazo esters with hydroxyl and thiol compounds,realizing efficient the construction of C-O and C-S bonds.The details are summarized as following:（1）Catalytic O-H insertion reactions between diazoesters and phenols using surface modified sewage sludge as catalyst.In air and under heating conditions,the surface modified sewage sludge（SW-Ⅰ）was used as a catalyst for the O-H insertion reactions of diazoesters and phenols,realizing the construction of C-O bonds and providing the phenoxyacetate derivatives one-step.The high yields obtained（up to 85%yield）,as well as the successful demonstration of a gram-scale reaction,confirming the potential for industrial application.On the other hand,SW-Ⅰ is also applicable with the natural phenols with compelling biological activity,affording the O-H insetion products of magnolol and honokiol,and giving the meta C-H insertion products of eugenol.Furthermore,the structures of O-H and C-H insertion products were further confirmed by single-crystal X-ray analysis.It should be noted that the majority O-H insetion products have good anti-tumor and anti-inflammatory activities.The IC₅₀ values indicated that the O-H insetion products 2-7a(IC₅₀=16.80μM)and 2-7c(IC₅₀=16.48μM)had better inhibition for tumor cell A-549 than positive control DDP(IC₅₀=20.62μM),which has the potential to become a drug and with high application value.（2）Catalytic C-C coupling reactions of diazoesters and arylboronic acids using surface modified sewage sludge as catalyst.In air and under heating conditions,SW-Ⅰ catalyzed the C-C coupling reactions between diazoesters and arylboronic acids,constructing the C-C bonds and forming the diarylacetate derivatives one-step,the highest yield up to 85%.Under standard conditions,the alkyl migration reactions of 3-diazochromanone compounds could also be achieved,and the products structure were further confirmed by single-crystal X-ray analysis.（3）Catalytic homogeneous O-H insertion reactions of diazoesters using small molecule acid as catalyst.We directly chose the conomical and accessible CF₃SO₃H as a homogeneous catalyst,successfully achieving the O-H insertion reactions between diazo esters and hydroxyl compounds（including:phenols,alcohols,water and oximes）.The high yields（up to90%yield）and a gram-scale reaction of this method may have the potential for industrial application.（4）The homogeneous S-H insertion reactions of diazoesters inducing by small molecule acid.We expanded the application range of small molecule acid,and using the conomical CF₃SO₃H as catalyst for the homogeneous S-H insertion reactions between diazoesters and thiols,realizing the construction of C-S bonds,the highest yield up to 91%.SW-Ⅰ was used as catalyst in both contents（1）and（2）,which is widely distributed,low-costand and eco-friendly.The reaction with available raw materials,mild reaction conditions and good yields,achieving the reuse of waste resources and alleviating the problem of difficult urban sludge treatment at the same time.It should be noted that the above catalytic system meets the purpose of green chemistry.