Synthesis of Aryl-methylene Ethers through Pd(0)-Catalyzed Coupling between Hydrobenzoxazoles and Dichloromethane

Abstract

Using dichloromethane (DCM) as the C1 feedstock, the first Pd(0)-catalyzed synthesis of aryl-methylene ether motifs from hydrobenzoxazoles (hydrothiazoles) has been reported. This protocol has exhibited an ample substrate scope (38 examples) and wide functional group tolerance. Aryl-methylene ether adducts have been successfully engaged in coupling with isocyanate to provide bis-iminoisoindolinones. In this reaction, DCM has served as a twofold electrophile for reaction with hydrobenzoxazoles via double C−Cl bond cleavage.A n aryl-alkyl ether is one of the most prevalent cores of top-selling drugs and is also a common motif found in drug candidates, natural products, and agrochemicals. 1 Among these aryl-alkyl ethers, aryl-methylene ether is a common subunit in many biologically interesting molecules and agricultural chemicals (Scheme 1, top). Conventional approaches for forging aryl-methylene ethers include nucleo-