Research On Palladium-catalyzed Cross-coupling Reactions Involving Isocyanides

The development of general and efficient methodologies for the synthesis of complexmolecular skeletons is the central focus of mordern organic chemistry. Isocyanides areimportant C1building blocks in organic synthesis and these molecules are known to take partin several of different types of reaction, especially finding particular usefulness in a widevariety of isocyanide-based multicomponent reactions.As know, CO is always used in palladium-catalyzed cascade reactions to increasemolecular complexity of the products by incorporating carbonyl groups and various importantheterocycles can be synthesised atom economically in this manner. Since isocyanide isisoelectronic with CO, it show similar reactivity towards palladium and undergo the samefundamental transformations. Surprisingly, the most reported achievements mainly focus onexploring the potential utility of the nucleophilicity and electrophilicity of isocyanides inmulticomponent reactions for the synthesis of nitrogen-containing compounds. However,migratory insertion of isocyanides in palladium catalysis is much less explored. Consequently,we presumed that palladium-catalyzed reactions involving isocyanide insertion should offertremendous opportunities for the synthesis of fine nitrogen-containing compounds.In this context, we describe herein our recent explorations in the field of isocyanideschemistry. An array of broadly useful coupling methodologies has been developed for theformation of C-C and C-N bonds etc. We further describe the application of these methods tothe syntheses of complex systems, including the amides and various nitrogen-containingheterocycles. Our research on palladium-catalyzed cross-coupling reactions involvingisocyanides has led to a series of new results which will be presented in the following fivechapters.In chapter two, a new and efficient method for synthesis of amides viapalladium-catalyzed C-C coupling of aryl halides with isocyanides is reported, by which aseries of amides were formed from readily available starting materials under mild conditions.This transformation could extend its use for synthesis of natural products and significantpharmaceuticals.In chapter three, we successfully realized a palladium-catalyzed one-pot cyclizationreaction to construct (3E)-(imino)isoindolin-1-ones and (3E)-(imino)thiaiso-indoline1,1-dioxides by introducing ortho-reactive functional groups on aryl halides. Under optimalconditions, the cyclization reaction afforded the corresponding products in good to excellentyields (up to93%) with high stereospecificity. Notably, this transformation successfully extends its application for synthesis of phenanthridins and dibenzooxazepins. This newsynthetic protocol not only builds up an application platform for palladium-catalyzed C-Ccoupling of aryl halides with isocyanides, but also opens atom economic and step economicsynthetic routes for nitrogen-containing heterocyclic compounds with wide functional groupcompatibility.In chapter four, a robust route to4-amine-benzo[b][1,4]oxazepines relying upon apalladium-catalyzed tandem reaction of o-aminophenols, bromoalkynes and isocyanides hasbeen developed. This chemistry presumably proceeds through the migratory insertion ofisocyanides into the vinyl-palladium intermediate as a key step.In chapter five, a Pd-catalyzed aerobic oxidation of o-aminophenols and isocyanides tothe synthesis of2-aminobenzoxazoles and3-aminobenzoxazines has been achieved under airatmosphere. The procedure constructs2-aminobenzoxazoles and3-aminobenzoxazines withmoderate to excellent yields and a broad substrate scope. Apart from experimentalsimplicity, this methodology has advantages of mild reaction conditions and easily accessiblestarting materials. Furthermore, the utility of this method is also successfully applied to thesynthesis of other types of useful nitrogen heterocycles.In chapter six, a robust and regioselective palladium-catalyzed intermolecular aerobicoxidative cyclization of2-ethynylanilines with isocyanides to the synthesis of4-halo-2-aminoquinolines is reported herein. The procedure constructs various4-halo-2-aminoquinolines with moderate to excellent yields and a broad substrate scope.Furthermore, this process could be easily extended to synthesis of various6H-indolo[2,3-b]quinolines via an intramolecular Buchwald-Hartwig cross-coupling reaction in two-stepone-pot manner.