Synthesis Of Functionalized1,2-dihydropyridines And Pyridine Derivatives Bearing Quaternarycarbon Centers

Pyridines are among the most prevalent heterocyclic structuralunits inpharmaceutical and agrochemical targets, as well as inmaterials science. Pyridinesalso provide convenientsynthetic precursors to chiral dihydro-and tetrahydropyridines,as well as piperidines, which continue to be of interest asintermediates in alkaloidsynthesis, in NADH models, and as important biologically active structures.Dihydropyridines in turn may also be converted to substituted pyridines throughoxidation. The syntheses of these compounds have received considerable attentiondue to their importance. Reissert reaction of pyridine derivatives has been well knownto construct α-cyano substituted1,2-dihydropyridines which can beregarded as cyclicα-aminonitriles for several decades. In contrast to other α-aminonitriles bearing aα-hydrogen which are exceptionally versatile intermediates in synthetic chemistry andhave been widely used in the generation of multiple polyfunctionalstructures. Themetal-catalyzed carbocyanation reactions of alkenes are powerful tools forpreparingnitriles incorporating an β-quaternary center. However, this approachrequires harsh reaction conditions and has limited reaction models and functionalgroup compatibility. we have developed a metal-free catalytic intramolecularcarbocyanation reaction of alkenes using the synthesized2,2-disubstitutedfunctionalized dihydropyridines from reissert products of pyridine derivatives andMBH adducts as substrates, which provides facile access to functionalized pyridinesincorporating quaternary carbon centers.This thesis includes the following contents:(1) We have developed a tertiary amine-catalyzed allylic alkylation reactionbetween Reissert products of pyridine derivatives and MBH adducts. This methodprovided a facile synthetic route for the preparation of functionalized2,2-disubstituted-1,2-dihydropyridines incorporating quaternary carbon centers withgood to high regioselectivities and moderate enantioselectivities. In addition, thesynthetic application of the functionalized1,2-dihydropyridine product was also demonstrated.(2) We have developed a metal-free catalytic intramolecular carbocyanationreaction of alkenes, which provides facile access to functionalized pyridinesincorporating quaternary carbon centers. The substracts with various substituents werewell tolerant. In addition, the method can be accomplished via a one-pot reaction fromavailable Reissert products of pyridine derivatives and MBH adducts, In this manner,functionalized pyridines can be readily obtained.