Study On New Synthetic Methods For Isothiocyanates And Indolone Derivatives

Isothiocyanates and indolone derivatives have a wide range of biological activities,which are important skeletons for the construction of natural products and synthetic drugs.These structural units are prevalently found in many natural products and antitumor drug molecues.Therefore,the development of new methods for the efficient synthesis of isothiocyanates and indolone compounds is of great significance.The research content of this paper is divided into four parts:?1?Recent progress in the synthetic methods for isothiocyanates is summarized.The synthetic progress on 3-substituted indolone derivatives is also reviewed based on the catalytic strategy such as,Pd,Cu,or other metals,and metal-free protocol.?2?The second part focuses on the development of new isothiocyanating reagent,sodium trifluoromethanesulfinate?Langlois reagent?,as a safe,stable,solid-state agent,was found to be an efficient isothiocynanating agent for the transformation of organic amines to the corresponding isothiocyanates.In the presence of CuI and diethyl phosphite,CF₃SO₂Na underwent the deoxygenation and defluorination processes to generate carbonothioic difluoride,which was captured by primary amines to form isothiocyanates.This reaction method has good functional groups compatibility.Both aromatic amines and aliphatic amines are suitable for this transformation.The results show that CF₃SO₂Na is an effective thiophosgene surrogate,which has some advantages such as safety,low toxicity,and stability.It is believed that the isothiocyanation protocol has important academic value.?3?3-hydroxyindolone is an important class of drug;leading skeleton.Rapid construction of 3-hydroxy indolones via a carbon-hydrogen bond activation pathway remains a challenge.In this project,a variety of?-aminoacetophenone derivatives are designed.The combination of Pd?OAc?₂ and AgOAc was found to be an effective catalytic system for tandem C-H cycloaddition and oxidation of?-aminoacetophenone derivatives,providing a range of 3-hydroxyindolones.The isotope labeling experiment shows that the oxygen atom in the amide comes from water.A possible mechanism is also proposed.?4?A radical cyclization of N-methyl-N-phenylpropynylamide into isatins through oxidative cleavage of carbon-carbon bond has been developed.Herein,both tert-butyl nitrite and NaNO₂/Oxone were found to be effective oxidizing radical initiators for the cleavage of carbon-carbon triple bonds.The in-situ formed nitrogen dioxide radicals not only play the role of radical initiators,but also a nitration agent.Thus a nitration process occurred along with the cyclization,affording isatins and nitrated isatins.Control experiments were conducted to elucidate the radical reaction mechanism.This is the first example of oxidative radical C-H cyclization strategy for the synthesis of isatin via the cleavage of carbon-carbon triple bonds.