Intermolecular Hydrogen Abstraction Reaction between Nitrogen Radicals in Purine Rings and Alkyl Ethers: A Highly Selective Method for the Synthesis of N‐9 Alkylated Purine Nucleoside Derivatives

Abstract

A highly selective method for the synthesis of N-9 alkylated purine nucleoside derivatives via an intermolecular hydrogen abstraction reaction between nitrogen radicals in purine rings and alkyl ethers was developed. Novel purine nucleoside derivatives were obtained with good to high yields in the presence of (diacetoxyiodo)benzene (DIB) and iodine in one-step reaction.

Photochemical C−H Amination of Ethers and Geminal Difunctionalization Reactions in One Pot

“…Recently, radical‐based oxidative methods were explored for the amination of ethers . Following up on intramolecular oxidative radical C(sp 3 )−H amination of alkyl sulfonamides mediated by iodobenzene diacetate/I 2 , the Crabtree/Gunnoe and Guo/Qu, and Lin groups developed similar methods for the intermolecular amination of ethers with trichloroethyl sulfamate C or purine bases D . More recently, Buslov and Hu reported oxidative aminations of ethers with sulfonamides or carboxylic amides E , as well as nitrogen heterocycles using diphenyliodonium salts as the stoichiometric oxidant in the presence of NaH as a base .…”

Transition Metal‐Free Intermolecular α‐CH Amination of Ethers at Room Temperature

“…Guo and co‐workers developed the metal‐free direct alkylation of purines with tetrahydrofuran (THF) and ethers, but the reactions required illumination and heating at 70 °C and only purines were alkylated 17. Ochiai and co‐workers reported metal‐free α‐CH amination of ethers, but only the triflylamino group could be transferred 18.…”

Efficient Synthesis of α-Branched Purine-Based Acyclic Nucleosides: Scopes and Limitations of the Method

“…N -Alkoxyalkylation of nucleobases with cyclic or aliphatic ethers was performed under the catalyzed (CuCl 2 or n -Bu 4 NI) peroxide-promoted ( t -BuOOH) coupling conditions giving preferentially N -9 alkylated purine derivatives in moderate to high yields [ 23 , 24 ]. Another efficient and highly selective method for the synthesis of N -9 alkylated purine nucleosides exploited a reaction between purines and alkyl ethers in the presence of (diacetoxyiodo)benzene and iodine [ 25 ]. Finally, asymmetric synthesis of purine acyclonucleosides containing a hemiaminal ester moiety was reported via a three-component reaction of purines, aldehydes, and acid anhydrides [ 26 ].…”