Transition Metal-Catalyzed Lactam Synthesis Based On Ynamides And Dioxazolones

Multiple-substituted lactams,which widely found in natural products and bioactive compounds,are one of the most important motifs with great synthetic value.However,the traditional construction protocol for lactam derivatives were low atom-economical and accompanied by a large number of side products.The deficiencies were limited its commercial applications overwhelmingly.Therefore,in this thesis,two strategies for constructing multiple-substituted lactams with high atom-economical using transition metal catalysis were developed.In first part,we described herein novel yttrium/zinc-catalyzed tandem alkyne hydration/intramolecular aldol reaction of carbonyl-ynamides and copper-catalyzed tandem alkyne hydration/intramolecular Mannich reaction of imine-ynamides with water.This protocol allows efficient and diastereodivergent synthesis of valuable differ substituted-3,4-dihydro-2-quinolones with high regio-,diastereo-and enantioselectivity.The reaction presumably involves the formation of metal enolate intermediates through the hydration of ynamides,and intramolecular cyclization with carbonyl-or iminegroup via aldol-type reaction or Mannich-type reaction,respectively.In second part,a series of spirolactam derivatives were synthesized efficiently and highly enantioselectively by the dearomatization of intramolecular naphthols with iridium nitrene intermediates produced from the decomposition of oxazolone substrates.This protocol realized the asymmetric catalytic dearomatization reaction based on the nitrene species,and enriched the construction method of chiral spirolactams.