Studies On The Synthesis Of Nine-Membered N-Heterocycles From N-vinyl Nitrones With Alkynes

Nine-membered N-heterocycles are a significant class of medium-sized Nheterocycles,existing in a broad range of bioactive molecules,natural products,pharmaceuticals,and materials science.It has extensive applications in drug synthesis(such as anticancer drugs,anti-inflammatory drugs,etc.)and functional materials.At the same time,nine-membered N-heterocycles are also important synthetic blocks in organic synthesis reactions,and are important intermediates for constructing various other novel nitrogen heterocyclic compounds and natural products.In this paper,Nvinyl-α,β-unsaturated nitrones and alkynes via [3+2] cycloaddition and [3,3]rearrangement reaction to construct nine-membered N-heterocycles and polysubstituted 1-pyrrolines were mainly discussed.This thesis is divided into two parts:In the first part,we developed a method for constructing chiral nine-membered Nheterocycles using a chiral auxiliary induction strategy.A variety of chiral ninemembered N-heterocycles were prepared with high diastereoselectivity through a silver(Ⅰ)-catalyzed [3+2] cycloaddition and [3,3] rearrangement of N-vinyl-α,β-unsaturated nitrones and chiral 3-propioloyloxazolidin-2-ones.Then,pyrrolizine carboxylate esters was obtained with high enantioselectivity by the removal of chiral auxiliary.The stereochemistry of the nine-membered N-heterocycles was controlled via [3,3]-rearrangement by chiral oxazolidinone-auxiliary through a boat-like transition state.Studies showed that the chiral oxazolidinone auxiliary not only controlled the stereochemistry of [3,3]-rearrangement to form nine-membered ring,but also had great inpact on the N-O bond cleavage to form the polysubstituted pyrrolizines.In the second part,we have developed a simple and efficient strategy for synthesizing quinazolinone-substituted 1-pyrrolines.A variety of quinazolinonesubstituted 1-pyrrolines were prepared through a nickel(II)-catalyzed [3+2]cycloaddition and [3,3] rearrangement of cinnamaldehyde-derived N-vinyl-α,β-unsaturated nitrones and alkynes with quinazolinone dominant skeleton.In this study,we found that the different structures of nitrone substrates had a significant impact on the structure of the generated products.When cinnamaldehyde-derived N-vinyl-α,β-unsaturated nitrones were used to react with 2-alkynylquinolinone,quinazolinonesubstituted 1-pyrrolines were obtained with high diastereoselectivity.And when chalcone-derived N-vinyl-α,β-unsaturated nitrones were used,polysubstituted pyrrolizines were obtained in moderate yields.Two types of [3+2] cycloaddition and[3,3] rearrangement reaction mechanisms can be controlled by the steric hindrance effect of nitrones.