Pd(?)-catalyzed C-H Lactonization (Lactamization) Applying On Total Synthesis

Palladium-catalyzed C-H activation has attrated increasing attention as a novel strategy in modern organic synthesis.In this dissertation,we summarized the history and current status of this field,especially for directed C-H functionalizations.Considering the difficulty for the derivation of directing groups used so far,our solution is to develop new synthetic methods of heterocycles via C-H functionalizations,in which the directing groups were used also as building blocks.Firstly,we developed a highly atom-economic carboxylic-directed C-H activation/C-0 cyclization catalyzed by Pd(II)to construct biaryl lactones.With mono-protected amino acid ligand added to improve the catalytic reactivity of the C-H cleavage step,the reductive elimination,which is the primary problem in C(sp2)-O bond formation,was accelerated via Pd(II)/Pd(IV)catalytic cycle with iodobenzene diacetate used as an oxidant.The effeciency of this new method was demonstrated as key steps for two times in the total synthesis of cannabinol.Next,we developed a Pd(II)-catalyzed amino-directed carbon monoide insertion to synthesis isoindolin-1-one.Using TEMPO as the key oxidant,we furnished the lactams through Pd(II)-catalyzed C-H activation/CO insertion in sterically hindered amines.This new method was then applied to study the total synthesis of spiropachysine as a key step.