Studies On The Boron-catalyzed β-functionalization Of Cyclic Tertiary Amines

C-H bond is one of the most common and important basic structural units in nature,which exists extensively in various natural active substances,synthetic materials,including hydrocarbons（low grade alkanes,aromatic hydrocarbons and polyaromatic hydrocarbons）,complex organic compounds and biopolymers.Therefore,the activation functionalization of C-H bond is an important means to construct complex compound molecules.At present,the activation of the catalytic inert C-H bond has been more transition metal catalytic systems.However,due to its own defects,it is expensive and not friendly to human body and environment.Therefore,chemists developed a non-transition metal catalytic system for catalytic activation of the inert C-H bond.The reports of alkali catalysis and the activation of exogenous oxidants are relatively more.In recent years,scientists began to develop the method of catalytic activation of the inert C-H bond of borane,especially the activation of the inert Csp³-H bond of amine compounds to achieve the direct functional group.This novel catalytic system requires no transition metal activation,no addition of exogenous oxidants,and the reaction conditions are relatively mild,which is of great significance for the efficient green synthesis of complex amine compounds,and provides a new idea for the fixed-point modification of amine drugs at a later stage.At present,catalytic activation of the inert C-H bond has been reported mainly transition metal catalytic systems.However,the current research of this system mainly focuses on the activation of the aminoα-Csp3-H bond to achieve the functionalization of the aminoαposition,and there are few studies on the direct functionalization of theβposition of amine compounds catalyzed by borane.In this paper,under the condition of borane catalysis,a"borrow hydrogen"tandem reaction strategy was designed to borrowing hydrogen strategy to the direct functionalization of inertβ-C-H bond of the cyclic tertiary amine,and the 3-substituted pyrrolidine derivatives were synthesized efficiently.the specific contents are as follows:In the first part of this paper,the functionalization of cyclic tertiary amine inertβ-C-H bond catalyzed by borane B（C₆F₅）₃ are mainly described.Based on the strategy of"hydrogen borrowing reaction",the series reaction of"oxidation/nucleophilic addition/reduction"between indirubin and tertiary amine was successfully realized.A series of 3-enyl substituted pyrrolidine derivatives were synthesized with good yield and good cis-inverse selectivity under mild reaction conditions and wide application range of substrates.This non-transition metal-catalyzed,oxidation-free intermolecular redox reaction provides a new method for the direct functionalization of cyclic tertiary amines.Due to the influence of the electron effect,the highly efficient and highly selective synthesis of-substituted pyrrole derivatives is a difficult problem.In the second part of this paper,based on the hydrogen transfer strategy,the dehydrogenation coupling reaction between saturated cyclic tertiary amine and indirubin catalyzed by borane B（C₆F₅）₃was realized for the first time by one-pot method,and a series ofβ-substituted-pyrrole derivatives were synthesized with excellent yield.The reaction is based on cheap indirubin and pyrrolidine,which is easy to operate,effectively avoids the selectivity of C-2 and C-3 in the synthesis of substituted pyrrole derivatives,and provides a new idea for the efficient synthesis of substituted pyrrole derivatives.