Aziridine Synthesis Of Oxazolines Via Electrophilic Ring Expansion Of Aziridines With Diazoketoesters

Aziridines are common three-membered heterocyclic organic compounds that are widely used in the synthesis for natural products,pharmaceuticals,and intermediates.Because of the ring tension in the molecular structure,they are highly susceptible to ring opening and ring expansion reactions.Aziridines are commonly used synthons in organic synthesis for the construction of various nitrogen-containing organic compounds.In this dissertation,alkyl 2-(oxazolin-2-yl)alkanoates were synthesized from N-unprotected 2-arylaziridines and alkyl2-diazo-3-oxoalkanoates.The benzo-δ-phosphonolactams were synthesized from benzylphosphonochlorides and cyclic imines as raw materials,analogs of aziridines with similar nucleophilicity.Firstly,a variety of alkyl-2-(oxazolin-2-yl)alkanoates were synthesized from N-unprotected 2-arylaziridines and alkyl 2-diazo-3-oxoalkanoates.Oxazolines and their derivatives are an important class of nitrogen-and oxygencontaining five-membered unsaturated heterocycles,which are ubiquitous in some natural products and drugs.Under microwave heating,alkyl 2-diazo-3-oxoalkanoates undergo a Wolff rearrangement reaction to generate α-oxoketenes followed by electrophilic ring expansion reaction with aziridines to afford alkyl-2-(oxazolin-2-yl)alkanoates.The reaction is simple and clean without any additives and catalysts,and can also be used for the synthesis of 2-(oxazolin-2-yl)alkanamides and 1-(oxazolin-2-yl)alkylphosphonates.In addition,a formal [4+2] annulation reaction between cyclic imines(dibenzo[b,f][1,4]oxazepines)and benzylphosphonochlorides was used to prepare various benzo-δ-phosphonolactams.In the reaction,the imines first nucleophilically attack on the phosphorus atom of benzylphosphinic chlorides to form phosphonylated intermediates through addition-elimination.Then a strong base abstracts the α-proton of phosphonyl group to generate phosphorylcarbanion intermediates,making the adjacent benzene electron-rich.Due to the influence of electronic effects,the generated iminium undergoes an intramolecular Friedel-Crafts alkylation with the benzene ring followed by further aromatization to yield benzo-δ-phosphonolactams.It provides a new method for the synthesis of novel phosphonolactam compounds.In summary,in this dissertation,studies on the synthesis of nitrogencontaining heterocycles from aziridines and their analog seven-membered cyclic imines with similar nucleophilicity was carried out.New methods for the syntheses of oxazolines and β-phosphonolactams were developed.It provides new synthetic routes for synthesis of diverse nitrogen-containing heterocycles.