Cu(OTf)₂‐Catalyzed Dehydrogenative C–H Activation under Atmospheric Oxygen: An Expedient Approach to Pyrrolo[3,2‐d]pyrimidine Derivatives

Abstract

A new dehydrogenative C–H activation of uracil in an open atmosphere was developed to synthesize pyrrolo‐pyrimidines, which are potentially bioactive molecules. This new approach establishes the selective catalytic activity of Cu(OTf)2 to accomplish the uracil C‐6–H activation.

Oxidative coupling reactions for the functionalisation of C–H bonds using oxygen

“…A similar approach was reported in 2013 by the group of Majumdar for the cyclisation of various uracil amides (Scheme 24). 59 In this case, Cu(OTf) 2 was found to be the optimal catalyst and the presence of a base was required. Oisaki et al have utilised molecular oxygen as terminal oxidant for the Mn-catalysed cyclisation of indoles with malonic ester residues to produce ring fused indoles.…”

Cu-Catalyzed C–H Activation Reaction: One-Pot Direct Synthesis of Xanthine and Uric Acid Derivatives from 5-Bromouracil

“…We envisioned that if we would manage to activate uracil C6-H bond 20 to form C-N bond, a possible disconnection could be hypothesized which would bring high degree of variability into the core structure of xanthine derivatives. Our goal was to carry out an amidination reaction on 5-halo uracil with amidine and then, to explore the amidinated product for a C-H activation study (Scheme 2).…”

“…The first method involves multiple steps, from 5,6-disubstituted uracil and amidines, 18a in the second method 5,6-diaminouracil was microwave irradiated with triethyl orthoformate (not shown here), 18b and the third way involves treating sodium azide with 5-halo-6-substituted uracil (Scheme 1). 19 We envisioned that if we would manage to activate the uracil C6-H bond 20 to form a C-N bond, a possible disconnection could be hypothesized which would bring high degree of variability into the core structure of xanthine derivatives. Our goal was to carry out an amidination reaction on 5-halouracil with amidine and then to explore the amidinated product for a C-H activation study (Scheme 2).…”

Catalytic C–H bond functionalisation of purine and pyrimidine nucleosides: a synthetic and mechanistic perspective

“…Furthermore, Roy, Majumdar and co-workers 79 employed the idea of dehydrogenative C-H activation and have recently reported a novel copper-catalysed intramolecular cyclisation reaction under atmospheric oxygen to provide an easy access to pyrrolopyrimidines (Scheme 36). The authors propose a single electron transfer type mechanism that could be acting in such processes.…”