[4+2]Cycloaddition Reactions Of 3-methylene Azetidine

The C-N bond is one of the most abundant chemical bonds in nature and it is widely found in organic molecules and biological macromolecules.Therefore,the formation and transformation of C-N bonds has attracted a great deal of attention among chemists.The C-N bond broken of azo rings can provide both a nitrogen source and a carbon source simultaneously,which provides a good condition for the synthesis of nitrogen-containing heterocyclic compounds.The alkene functionalized strained nitrogen heterocycle has received extensive attention due to the carbon-carbon double bond that can coordinate with the transition metal and can participate in the formation of stable cations,anions or free radicals.At present,there are two main types of substrates that are reported to be based on the cleavage of the tension ring allyl C-N bond to obtain a nitrogen(carbon)source:(1)compounds that contain methylene aziridine;(2)compounds that contain 2-vinyl aziridine.Their reaction strategy is to open the ring to produce[1,3]or[1,5]dipoles with metal catalyst(Lewis acid),and then complete the[3+X]or[5+X]cycloaddition reaction with CO,olefins and isocyanates.The application of this strategy to alkene functionalized azetidine is rarely reported.In this paper,we designed a 3-methylene azetidine type compound,and formed a novel[1,4]dipole with silver,achieving intramolecular and intermolecular[4+2]cycloaddition reaction.First,a silver-promoted oxidative cascade reaction of N-(hetero)aryl-3-methylene azetidines with carboxylic acids is reported.Acetyloxy functionalized pyridine rings,aromatic rings(or heterocyclic)fused pyridine ring compounds can be efficiently obtained by this method.Mechanistic studies reveal that silver salt is essential for the chemo-and regioselective intramolecular[4+2]ring expansion,sequential oxidative nucleophilic additions and oxidative aromatization.With this method the pyridine ring can be introduced modified to drugs and natural products.Furthermore,this method has also been applied to the synthesis of asymmetrical phenanthroline ligands.In addition,the traditional Diels-Alder reaction to construct N-hetero six-membered ring can only form intracyclic double bond,and we have used 3-benzylidene azetidine and aryl ethylene to achieve intermolecular[4+2]cycloaddition with the catalytic action of silver salt,highly selectivity construction of six-membered azacyclic with double bond outside.Substrate scope,mechanism studies,and synthetic applications are still in progress.