Highly enantioselective synthesis of lactam and sugar derivatives by chiral aminocatalysis and merging with transition metal catalysis

Sammanfattning: This thesis presented novel methodologies for enantioselectivesynthesis of highly functionalized lactam and sugar derivatives.Asymmetric organocatalysis, cooperative dual catalysis and one-pot multicomponent reaction strategies were applied for the construction of continuous and quaternary stereogenic center.In Chapter I, an unique strategy for enantioselective synthesis of bicyclic lactam N,S-acetals scaffolds was developed. The reaction intiates from an aminocatalyzed transformation. Next, the addition of thiol amine leads to the construction of bicyclic lactams via aimine/N,S-acetal formation/lactamization cascade sequence.Chapter II focuses on a stereodivergent synthesis of fluorinated lactams bearing two vicinal stereogenic centers by multicomponent reaction. The reaction proceeds via enantioselective Michael addition/imine formation/lactamization cascade process. The reaction solventused in the lactamizarion step gives switchable diastereoselectivity to the fluorinated quaternary stereocenter. DFT calculation revealed a mechanistic insight into the unexpected diastereoselectivity. The usefulness of fluorinated lactams was demonstrated in fluorinated drug analogue synthesis.Chapter III illustrates a new enantioselective allylic alkylation of acetonide protected trioses and furanosides by merging enamine catalysis with transition metal catalysis. An intrinsic sugar-assistedkinetic resolution mechanism between aldehyde and aminocatalystwas proposed and monitored in NMR studies.Chapter IV is about a new chiral amine-catalyzed C4’ α-aminomethylaction of furanoside and nucleoside derived C5’ aldehydes. The C4’ aminomethyl functionalized furanoside precursors have potentials fornew nucleoside analogue synthesis.