Tandem Cyclization Reaction Catalyzed By Transition-Metal For Construction Of Heterocyclic Compound Skeleton

With unique physiological and pharmaceutical activity, nitrogen-heterocyc lie compounds are prevalently presented in numerous natural products and pharmaceutically relevant molecules, along with application in the field of pesticides, herbicides, and fungicides. As a consequence, the development of efficient methods to construct different kinds of nitrogen-heterocyc lie skeletons will be of significant synthetic importance, along with great scientific and practical value. In this thesis, we are mainly focused on the development of new tandem cyclization reactions catalyzed byAu (I) and Pd(II) complexes to access different nitrogeneous heterocycks.The chiral 1,2,3,4-tetrahydroquinoline not only represents a prevalent skeleton in numerous naturally occurring alkaloids and artificial bio-related molecules but also emerges as aprivileged building block in drug discovery, thus is considered a privileged structure. The presence of only 0.2 mol% of chiral gold phosphate generated in situ from IMesAuMe and a chiral phosphoric acid, allowed the 2-(2-propynyl)aniline derivatives to undergo intramolecular hydroamination and to generate optically active tetrahydroquinolines in moderate to good yields and with excellent enantioselectivities. Notably, the gold catalyst acts as either a π-Lewis acid to promote the intramolecular hydroamination or a (?)-Lewis acid to accelerate the asymmetric transfer hydrogenation.Hetero-Die Is-Alder (HDA) reaction has been considered one of the most efficient methods for the construction of multifunctionalized heterocycles. Among numerous enantiose lective HDA reactions, those with diazene derivatives as dienophiles were able to produce optically active tetrahydropyridazines. A chiral gold complex of phosphoramidite was found to be capable of efficiently catalyzing an asymmetric cascade protocol, which consists of a dehydrative cyclization reaction to give diene intermediates and a subsequent aza-Diels-Alder reaction with diazene substrates, giving rise to chiral pyridazine products in good yields and up to 82% ee.1,3-dipolar cycloaddition is one of the most efficient methods for construction of heterocyclic compounds. We have created a cycloisomerization and dipolar cycloaddition reaction cascade between nitrone alkynes and electron-deficient olefins catalyzed by10 moP% of a simple palladium (Ⅱ)complex. Via the oxygen-atom transfer of alkyne proceeded by the formation of a-oxo palladium carbenoid, tricylic hetero-products could be obtained with good yields and diastereoselectivity.