Study On Sp~3 C-H Functionalization Of Tetrahydrofuran Via Radical Process

Tetrahydrofuran as a basic and privileged raw material has numerous applications,involving in synthetic chemistry,and functional material through ring-opening polymerization.Tetrahydrofuran derivatives are also significant structural motifs,spreading in many natural products and pharmaceuticals.Consequently,the development of synthetic methodologies for tetrahydrofuran derivatives is of great significance to organic and medicinal chemists.In general,the most of the tetrahydrofuran derivatives were assembled mainly via the cyclization reaction of predesigned starting materials with the required functional groups and the prefunctional substrates,which limited their broad applications.Hence,development of highly efficient strategy to acquire substituted tetrahydrofuran is dramatically meaningful.In this paper,we mainly study on the three-component reaction for efficient synthesis of a series of α-indole,β-sulfonyl tetrahydrofuran derivatives with good yields starting from 2-phenylindole,p-methylbenzenesulfonylazide and tetrahydrofuran under the presence of tert-butyl peroxybenzoate(TBPB).The reaction is heated to 105℃ for 16 h.The method has great advantages in simple reaction conditions,easy operation,high atom economy,and realizes the difunctionalization of the sp3 C-H bond of tetrahydrofuran.The significance of this protocol is not only its convenient construction of tetrahydrofuran derivatives with multiple substituents,but also provides a practical and feasible example for the direct difunctionalization of the sp3 C-H bond of tetrahydrofuran to construct highly tetrahydrofuran derivatives.Scheme 1 Based the previous reports and results obtained,a possible reaction mechanism was proposed as shown in Scheme 2.