Construction Of Pyrazoloquinazoline Derivatives And Benzazepine-Bridge Skeleton With Thiolated Quaternary Carbon Centers

Heteroatomic quaternary carbon centers are widely found in natural products,drugs,and biologically active drug candidates.In recent years chemist has focus on developing effective methods to construct quaternary carbon centers On the other hand,quinazoline cocyclic compounds,as a natural products skeleton,are widely synthesized due to their good activity.Therefore,It is of great significance to find an efficient and simple method to synthesize this framworks.Aza-bridging-ring skeletons are widely present in various alkaloids and drugs.The synthesis of aza-bridging-ring skeletons have long been a hot topic in an efficient way.Some of the compounds showed excellent activity,which makes this research has great potential value.Base on previous work,We have designed a method to synthesize α-thioalkyl substituted phenylpropanal.In the assembly of α-thioalkyl substituted phenylpropanal adducts and containing an azomethine imine moity,using an enolate activation strategy,which undergo an[4+2] cycloaddition by base-catalyzing.Affording a range of Pyrazo-quinazoline frameworks containing S atom quaternary carbon centers in good yield(up to 99% yield)with excellent distereoseletivity(from 3:1 to >19:1 dr).The amplification and derivatization reactions confirmed the utility of the compounds.Moreover,the excepted discovery of benzodiazepine bridging ring compounds,sulfurcontaining alkyl quaternary carbon centers,was transformed by quinazoline derivatives.We also propose a possible reaction mechanism.After a series of conditions screening for rearrangement reaction,the skeleton of bridge ring with sulfur alkyl quaternary carbon center was effectively constructed with excellent substrate scope.The rearrangement reaction will provide a new method to construt benzodiazepine bridge ring skeleton with sulfur alkyl quaternary carbon center.