Study On The Structure-Reactivity Relationship Of Domino Aryne Precursors

Multi-substituted aromatic structures are commonly found in natural products,pharmaceutical molecules,agrochemicals,dyes,and fine chemicals.Therefore,the efficient synthesis of polysubstituted aromatic compounds is important for improving human living standards and social development.A large number of literatures have reported on this work,in which the method via benzyne intermediate has significant advantages.It can realize ortho-difunctionalization of benzene ring under transition-metal-free conditions,and own the advantage of step economy.Synthetic chemists also achieved polysubstituted arenes by using benzdiyne and benztriyne equivalents.Our group has been dedicated to solving the shortcomings of traditional benzyne chemistry and exploring its new reaction modes as well as application potential.In order to construct polysubstituted aromatics efficiently and conveniently,we independently designed and prepared the first-generation domino aryne precursor（TPBT）and the second-generation domino aryne precursor（TTPM）,and developed several tandem process to realize multifunctionalization of arenes.In particular,a new domino aryne nucleophilic and Diels-Alder cascade process was developed,and the ergot alkaloid skeleton was efficiently synthesized by this method.It shows the potential value of this strategy in the synthesis of natural products.Moreover,we further explored structure-reactivity relationship of the second leaving group on a variety of1,2-benzdiyne precursor.It was found that a new generation of domino benzyne precursors with 2,6-difluoro substituted phenyl sulfonates can accomplish the nucleophilic and Diels-Alder cascade process under milder conditions.The new benzdiyne precursor(TTPB^2F)was more advantageous than others under a lower temperature,it could fill the leaving-ability gap between the highly active OTf group（TPBT）and the inert OTs group（TTPM）.At the same time,this 1,2-benzdiyne precursor can efficiently achieve the tandem nucleophilic process of sulfonamide,and thiobenzamide.In addition,the 1,2-benzdiyne precursor containing 2,4-difluoro substituents can achieve nucleophilic-ene cyclization reactions at a lower temperatures,breaking limitations of higher temperature conditions for this conversion reported previously.A new generation of domino aryne-TTPB^2F difluoro-substituted benzdiyne precursor was used to successfully achieve various domino reaction transformations from low to high temperatures.It shows an effective role in regulating domino aryne reaction.