Azidly Radical Cyclization And Discovery Of Ynamide Coupling Reagents

Click reaction has evolved into an important method for constructing functional molecules because of its wide range of applications,the mild and simple reaction conditions,highly selective and efficient,easy to handle and many other advantages.We have developed a novel approach to NH-1,2,3-triazoles via an oxidative “click reaction” between alkynes and sodium azide,which involved a cascade initiated by the homolytic addition of the azidyl radical to C-C triple bond of non-activated alkynes.Meanwhile,a novel class of coupling reagent ynamides have been developed for facilating amide and peptide bond formation.The activation of carboxylic acids was accomplished via the hydroacyloxylation of ynamides to offer ?-acyloxyenamide,which acts as an active ester.Both the aminolysis of ?-acyloxyenamide and the hydroacyloxylation of ynamide proceeded in “click” manners and thus enabling ynamide to act as a dehydration reagent to facilitate amide bond formation from carboxylic acid and amine directly.This thesis is focused on the following two parts:1.Reaction between nitrogen-centered radicals and unsaturated C-C bonds is an effective synthetic strategy for the construction of nitrogen-containing molecules.Herein,the first example of reactions between azidyl radicals and alkynes is described.We reported the first reaction of azide radicals with alkynes and realized a transitionmetal-free "click reaction" between multiple alkynes and sodium azide via a radical strategy.It is foreseeable that the results reported here will spur the application of azidyl radical chemistry and shed light on the design of new reactions between N-centered radicals and alkynes in the future.2.Amide bond is one of the most important chemical bonds in nature.Proteins and peptides with important biological activity are also formed by linking amino acids through amide bonds.Herein,we have successfully developed a two-step,one-pot strategy for amide and peptide bond formation by employing ynamide as a novel coupling reagent under extremely mild reaction condition.The ynamide coupling reagent canbe prepared easily from readily available chemicals and are stable to air and moisture.More important,no epimerization/racemization of alpha-chiral acids was detected by employing ynamide as a novel coupling reagent.The ynamide coupling reagent not only effective for dipeptide and tripeptide synthesis but also can be used for peptide segment condensation.Therefore,development of ynamide coupling reagent is significant in academia as well as application.