Studies On Reaction Of Nitrones With Allenoates To Construct 1.2-fused Indoline Compounds

Substituted indoles are not only common structural scaffolds existing in natural products,pharmaceuticals,and biologically active compounds,but also one of the most important N-heterocycles in organic synthesis.Nitrone,as an important1,3-dipole,has been one of the most attractive building blocks for the construction of indole scaffolds or other azocyclic N-heterocyclic rings.In particular,the study of the cycloaddition reaction of nitrone and allenoate is one of the most effective strategies to construct indole derivatives.In this paper,we study the synthesis of N-heterocyclic compounds by [3+2] cycloaddition and [3,3] rearrangement cascade reaction betweenα,β-unsaturated aryl nitrone and disubstituted allenoates.The practicability of the method was demonstrated by gram preparation,substrate transformation,and chiral indole compounds obtained by using chiral auxiliary.This study is divided into two parts:In the first part,we described a copper(Ⅱ)-catalyzed [3+2] cycloaddition/[3,3]rearrangement and retro-Mannish reaction process of N-aryl-α,β-unsaturated nitrones with disubstituted allenoates bifurcated to prepare various[1,3]oxazino[3,2-a]indolines and dihydropyrido[1,2-a]indolines in moderate to excellent yields.Mechanistic studies revealed that [1,3]oxazino[3,2-a]indoline was a kinetically favored product and dihydropyrido[1,2-a]indoline was thermodynamically favored product.Moreover,the reaction was easily performed at gram scales and chiral dihydropyrido[1,2-a]indoline could be obtained by using chiral auxiliary.The present method highlights broad substrate scope,good functional group tolerance,and diversity of indoline scaffolds with high diastereoselectivity.In the second part,we studied a palladium(Ⅱ)-catalyzed [3+2] cycloaddition/[3,3]rearrangement reaction process of N-aryl-α,β-unsaturated nitrones with disubstituted allenoates,followed by sodium borohydride/methanol reduction to prepare benzo aza-seven-membered ring compounds in moderate yield.The effects of catalyst,ligand,solvent,additive and temperature on the reaction were investigated.After exploring the range of substrates,it was found that the method was tolerant to thiophene,benzaldehyde,and nitrone derived from estrone.In this reaction,a chiral benzodiazepineone compounds can be obtained by using chiral auxiliary.