“All-Aqueous” Tandem Boc-Deprotection and Alkylation of N-Bocbenzimidazole Derivatives under Visible Light with Alkyl Aryl Diazoacetates: Application to Site-Selective Insertion of Carbenes into the N–H Bond of Purines

Abstract

Herein, we have reported a blue LED-induced tandem Boc-deprotection and NH-alkylation of benzimidazole derivatives with methyl aryl diazoacetates. The reactions occur in water at room temperature. The desired products are obtained in good to excellent yields. The putative mechanism of this reaction is discussed based on control experiments and supported by DFT studies. Additionally, the strategy is used to alkylate various purine derivatives via site-selective N1-alkylation to generate acyclic nucleoside analogues.

Visible photons as ideal reagents for the activation of coloured organic compounds

“…61 As a matter of fact, carbenes readily inserted into the N–H bond of carbazole, 279 dibenzoazepines, 279 and even purine derivatives, causing a site-selective N 1 -alkylation for the construction of acyclic nucleoside analogues. 280…”

“…61 As a matter of fact, carbenes readily inserted into the N-H bond of carbazole, 279 dibenzoazepines, 279 and even purine derivatives, causing a site-selective N 1 -alkylation for the construction of acyclic nucleoside analogues. 280 Another approach for the C-N bond formation involves the addition of the carbene onto a nitrile (used as the reaction medium). The carbene, in turn generated from visible-light photolysis of diazoacetate 81.1, was trapped by MeCN to generate the corresponding nitrile ylide 81.4, which upon proton transfer with a carboxylic acid (81.2) yielded a nitrilium ion 81.5, which was prone to undergo a nucleophilic attack by the carboxylate anion.…”