The Construction Of Novel Heterocycles Via The Reaction Involving Isocyanides

Isocyanides are compounds with the extraordinary divalent carbon atom. The synthetically most important property of isocyanides is the reactions with nucleophiles and electrophiles at the isocyanide carbon atom. Tha addition of nucleophiles and electrophiles lead to a-adducts. Most other functional groups in organic chemistry react with nucleophiles and electrophiles at the different centers. Only carbenes and carbon dioxide share this property with isocyanides. Owing to the unique property of isocyanides, the application of the reactions involving isocyanides in the synthesis of heterocycles has been focused in the recent years. In this thesis, recent reviews aiming at the developments of multi-component reaction nvolving isocyanides and palladium-catalyzed isocyanide-insertion reaction are summarized, and several novel protocols with isocyanides are developed for the synthesis of heterocycles.As a starting point, multi-component reaction involving isocyanides could be conducted to synthesize a wide range of heterocyclic compounds. A novel three-component one-pot synthesis of spirooxindoles from isocyanides, dialkyl acetylenedicarboxylate derivatives and N-substituted isatylidene derivatives through [3+2] cycloaddition has been developed. This protocol was conducted in THF without any catalysts and 72-92% yields were obtained. The synthetic alkyne-containing spirooxindoles could also be applied in the selective synthesis of triazole-containing spirocyclic compounds using copper azide-alkyne cycloaddition (CuAAC) reaction.Next, the multicomponent reaction involving isocyanides in combination with post-cyclization reactions has been developed for the synthesis of the novel heterocycles. Using 2-isocyanophenyl 4-methylbenzoate as a fragrant and stable convertible isocyanide, a new protocol for Ugi/De-Boc/Activation/Cyclization synthesis of 2,5-diketopiperazine derivatives in 40-66% yields has been newly developed, avoiding treatment of typically known offensive isocyanides. This one-pot procedure displays good functional group tolerance and operational simplicity. Combining the Ugi reaction with palladium-catalyzed ring opening reaction of furans for the synthesis of novel isoquinolinone and 1,2-dihydroisoquinoline scaffolds has been developed. The isoquinolinone and 1,2-dihydroisoquinoline derivatives with unsaturated carbonyl moiety may open up many opportunities for further functionalizations. Optimization of palladium-catalyzed ring-opening reaction of furans was conducted. Under the optimized reaction conditions, a series of isoquinolinone and 1,2-dihydroisoquinoline were synthesized with the two-step yields up to 63%.Finally, palladium-catalyzed isocyanide-insertion reactions were also investigated in this thesis. A pratical ligand-free palladium-catalyzed isocyanide-insertion reaction for the synthesis of phthalazino[1,2-b]quinazolinones from the readily obtainable quinazolinones with 65-86% yields have been developed. Easily handled and relatively low-cost Pd(OAc)2 was used as the catalyst without an additional ligand. The preparation of quinazolinones involved the cascade reactions of isatoic anhydrides, phenylhydrazines and 2-bromobenzaldhyde catalyzed by TsOH in one-pot. A novel and efficient domino process has been developed for the synthesis of 1,4-benzoxazepine derivatives from a range of readily accessible N-tosylaziridines,2-iodophenols and isocyanides with 42-85% yields. This process involved the aziridine ring-opening reaction with 2-iodophenol, followed by palladium-catalyzed isocyanide-insertion reaction. This methodology has several advantages such as simple handling, high yields, good regioselectivity and high atom-economy. An efficient and practical two-step process has been developed for the synthesis of 2-amino-4(3H)-quinazolinones via ring-opening of isatoic anhydride with amines and palladium-catalyzed oxidative isocyanide-insertion in one-pot. The successful utilization of various amines further increased the variation at the N-3 position of 2-amino-4(3H)-quinazolinones. This regioselective procedure could construct a wide range of 2-amino-4(3H)-quinazolinones in 49-81% yields. Furthermore, the methodology also had distinct advantages of easily accessible starting materials and operational simplicity.