Study On The Synthesis Of Chroman-4-one Derivatives Via Radical Cascade Cyclization

Dicarbonyl compounds are a kind of indispensable building block for the synthesis of many structurally specific heterocycles.For example,1,3-dicarbonyl compounds are essential precursors for the synthesis of isoxazoles and pyrazoles.1,4-Dicarbonyl compounds are frequently used in Paal-Knorr syntheses to access furans,pyrroles,and thiophenes,and 1,5-dicarbonyl compounds are often used in the preparation of pyridines.Chroman-4-one is a special structural core of many natural products and important bioactive molecules,these compounds display a wide range of biological activities.In the discovery and design of drug precursors,the chroman-4-one scaffold is an important intermediate and building-block in the synthesis of new lead compounds.Due to mild conditions,good selectivity,high efficiency,simple steps and high atomic economy,radical cascade cyclization has become one of the research hotspots in organic chemistry.By using 1,3-dicarbonyl compounds as radical precursors,a series of1,5-/1,3-dicarbonyl heterocycles,including chroman-4-ones,indanones,and2,3-dihydroquinolin-4-ones were synthesized via our wisely designed radical cascade cyclizationstartingfrom2-functionalizedbenzaldehydes?including2-allyloxybenzaldehydes,2-allylbenzaldehyde and 2-N?Ts?CH₂-CH=CH₂ substituted benzaldehyde?in the catalytic oxidation system of AgNO₃ and K₂S₂O₈,which provided direct precursors for the further synthesis of more complex polyheterocycles.After simple disposal,the newly obtained 1,5-/1,3-dicarbonyl heterocycles were further used directly to efficiently synthesize more structurally diverse polyheterocycles in a significantly more atom-and step-economical manner,mainly including chromenopyridines as well as isoxazole-or pyrazole-containing chroman-4-ones.Through the control experiments,we proposed two possible reaction pathways:Carboxylic acids are readily available and inexpensive compounds obtained from both natural and synthetic sources.Moreover,these compounds are easy to handle and stable to air and moisture.Hererin,we developed a convenient silver-catalyzed decarboxylative cascade radical cyclization of 2-functionalized benzaldehydes?including 2-allyloxybenzaldehydes and 2-N?Ts?CH₂-CH=CH₂substituted benzaldehyde?toward 3-alkyl-substituted chroman-4-one derivatives and2,3-dihydroquinoline-4-one derivatives using alkyl carboxylic acids as the alkyl radical precursors.Based on decarboxylative radical cascade cyclization,the construction of alkyl substituted heterocycles was realized effectively.