Transition-metal Free C-N Bond Formation from Alkyl Iodide via Halogen-atom Transfer (XAT): Dual Roles of Diazonium Salts

Abstract

The precise and effective construction of challenging C-N bond continues to be one part of the most significant goals in organic chemistry because of the universal applications of amines containing C-N bonds in pharmaceuticals, materials as well as agrochemicals. However, E2 elimination through classic SN2 substitution of alkyl halides with nitrogen nucleophiles often occurs and alkenes are generated as the major side-products especially when secondary or tertiary substrates are employed. Thus, formation of a challenging C(sp3)-N bond especially on tertiary carbon center remains highly desirable. Herein, we present a practically alternative approach to prepare primary, secondary and tertiary alkyl amines with high efficiency between alkyl iodides and electrophilic diazonium salts which are easily accessible and widely utilized in synthetic chemistry. This robust transformation only employs Cs2CO3 as the base promoting the halogen-atom transfer (XAT) process under transition-metal-free reaction conditions, thus providing a rapid and green method to assemble diverse C(sp3)-N bonds. And also, the reaction can be achieved by continuous-flow technology in large scare with Et3N was employed as organic base. Moreover, diazonium salts are found to serve as two important roles (alkyl radical initiator and amination reagent) in this process which was rarely explored in the previous radical reactions. Initial mechanism studies suggest this reaction undergoes through a halogen-atom transfer (XAT) between alkyl iodides and diazonium salts, resulting in the generation of the active alkyl radical which can couple well with diazonium cations to furnish the final products.