Lewis Acid-Catalyzed Electrophilic Aminomethyloxygenative Cyclization Of Alkynols With N,O-Aminals

Oxygen-containing heterocyclic compounds are ubiquitous in natural product,and widely exist in some important biological activities and drug molecules;Meanwhile the use of cyclization to synthesize valuable heterocyclic compounds is also one of the important research directions in organic synthetic chemistry.Therefore,the development of direct and effective strategies to achieve the synthesis of oxygenated heterocyclic molecules has long been a research focus of scientists.We find that alkyne amides are an important special structure of alkynes,due to the electrical influence of the nitrogen atoms substituted on the alkynes,the triple bonds are highly reactive.At the same time,an electron-withdrawing substituent such as an amide or a sulfonamide is attached to the nitrogen atom,so that the ynamide compound can ensure its stability on the basis of not affecting the reactivity.In recent reports on the conversion of ynamides,the ring-forming reaction provides a powerful tool for the synthesis of complex and useful molecules.Therefore,the cyclization reaction using ynamide is also a research hotspot.In this thesis,using hydroxyalkynamide and N,O-Aminals as raw materials,under the catalysis of Lewis acid,enable hydroxyalkynamide to realized the electrophilic amine methylation oxygenation cyclization reaction,which was established a new and efficient synthesis strategy for the construction of oxygen-containing heterocyclic compounds.Using synthetic hydroxyalkynoyl raw materials and oxyacetal as substrates,the optimal conditions of the reaction were determined through systematic condition screening:5 mol%zinc trifluoromethanesulfonate was used as a catalyst,methylene chloride as a solvent,and react for 12 hours at room temperature.Under this condition,we have concluding a regular cognition after systematically studied from the reaction performance of hydroxyalkynamides with different chain lengths and N,O-Aminals with various substituents(total of 30 substrates).These substrates showed good reactivity,in the above reaction,which could yielded 5-8 membered oxetane compounds with a yield of up to 94%.The reaction showed a wide range of substrate versatility and functional group compatibility.A five-membered ring and a seven-membered ring can be reacted in gram-scale reaction to basically obtain the target product in high yield.The cyclized product can be converted by simple functional group derivatization to generate a practical oxocyclic compound.