Study On The Asymmetric Reaction Of N-Alkyne/Allyl-β-Ketoamid

With the continuous development of the social economy and the increasing material demand of the people,synthetic chemistry has gradually played an increasingly important role.Especially since the novel coronavirus pandemic began,people further realized the important role of synthetic chemistry in the field of medicine.However,with the rapid development of synthetic chemistry in the past decades,environmental pollution and energy scarcity have become increasingly apparent.The main reasons are that many drug molecules or compounds currently have low synthesis efficiency,poor tolerance for functional groups,harsh reaction conditions,and the use of toxic and harmful starting materials.To address these issues,chemists have proposed the concept of green chemistry,which aims to improve the utilization of atoms,increase the synthesis efficiency of reactions,and reduce the emission of toxic and harmful substances from the perspective of atomic economy.And based on this,more and more green,efficient,and environmentally friendly synthesis methods have gradually been developed.Chiral 1,2,3-triazoles and chiral 2-piperazinone are highly active chemical skeletons,widely present in natural products and bioactive molecules.The drugs developed based on these two types of skeletons have played an important role in human health and disease treatment.However,there are still certain limitations in achieving chiral conversion through existing chemical synthesis methods.Therefore,we hope to combine the concept of green chemistry to efficiently synthesize chiral compounds of these two types of frameworks.1)Through asymmetric cycloaddition reaction of terminal N-propargyl-β-ketoamides and azide reagents,A green and efficient synthesis of 1,5-disubstituted chiral 1,2,3-triazole compounds was achieved.The direct synthesis of 1,5-disubstituted chiral 1,2,3-triazole compounds through asymmetric cycloaddition reactions has not been reported before.Therefore,even though these compounds play important roles in fields such as biomedicine,they can only be conjugated through multi-step conversion of chiral substrates.We used inexpensive copper salts and chiral ligands as catalysts to efficiently synthesize a series of 1,5-disubstituted chiral 1,2,3-triazole compounds with80-99% yields and 78-95% ees under mild reaction conditions.This method has the characteristics of being green,efficient,easy to operate,and highly tolerant of functional groups,meeting the requirements of environmentally friendly synthesis strategies.2)Through asymmetric cycloaddition reaction of non terminal N-propargyl group-β-ketoamides and azide reagents,A green and efficient synthesis of 1,4,5-trisubstituted chiral 1,2,3-triazole compounds was achieved.The direct synthesis of 1,4,5-trisubstituted chiral 1,2,3-triazole compounds through asymmetric cycloaddition has not been reported until recent years,but it relies on the conversion between specific substrates,and uses more complex metals and chiral catalysts,so there are still certain limitations.We used inexpensive copper salts and chiral ligands as catalysts to efficiently synthesize a series of 1,4,5-trisubstituted chiral 1,2,3-triazole compounds with 40-75% yields and 83-95% ees under mild reaction conditions.This method has the characteristics of being green,efficient,easy to operate,and highly tolerant of functional groups,meeting the requirements of environmentally friendly synthesis strategies3)Chiral 2-piperazinone compounds were synthesized by asymmetric reaction of N-allyl group-β-ketoamides with azide reagents.This type of compounds typically relies on the asymmetric reduction hydrogenation of pyrazine derivatives under high temperature and pressure for conversion.On the basis of the above work,by using inexpensive copper salts and chiral ligands as catalysts,under mild reaction conditions,a series of chiral 2-piperazinone compounds were synthesized with 36-80% yields and80-97% ees through asymmetric reactions of N-allyl group-β-ketoamides ketoamides and azide reagents.