The first synthesis of [2‐¹³C]phloroglucinol

Abstract

A fast and efficient synthesis of [2-13 C]phloroglucinol in six steps from acyclic, non-aromatic precursors is presented, with regioselective placement of a 13 C-atom in the aromatic ring. The 13 C-label was introduced by reaction of [ 13 C]methyl iodide with methyl 4-chloroformyl butyrate. Cyclization via an intramolecular Claisen condensation, followed by aromatization gave [2-13 C]resorcinol. Following subsequent methylation of the hydroxyl groups, the third hydroxyl group was introduced using an iridium-catalysed C-H activation/borylation/oxidation procedure. Demethylation then yielded the desired [2-13 C]phloroglucinol.

Facile Synthesis of Halogen Decorated para-/meta-Hydroxy­benzoates by Iridium-Catalyzed Borylation and Oxidation

“…The group of Smith and Maleczka has reported iridiumcatalyzed aromatic C-H borylation/oxidation route for the synthesis of meta-substituted phenols directly from the hydrocarbon feedstock. [34][35][36][37] This transition-metal-catalyzed reaction is highly selective for aromatic C-H activation in the presence of other functional groups and thus allows for the incorporation of various substituents including halogens into the final phenol products. Moreover, sterically governed regioselectivity observed in this C-H functionalization reaction is complementary to that obtained through the traditional electrophilic aromatic substitution and directed ortho-metalation approaches.…”

A gram scale synthesis of a multi-13C-labelled anthocyanin, [6,8,10,3′,5′-13C5]cyanidin-3-glucoside, for use in oral tracer studies in humans

“…Silyl enol ether 13, generated from acetophenone [3,5-13 C 2 ]12, was treated with mCPBA, and after in situ hydrolysis gave a-hydroxy-3,4-diacetoxy-[3,5-13 C 2 ]acetophenone 15 as illustrated in Scheme 4. 15,24 Glycosylation of 15 required avoiding the use of heavy metals such as mercury and silver 13,15,25 and therefore a BF 3 Á OEt 2 catalysed coupling of a-hydroxyacetophenone 15, using 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl trichloroacetimidate was employed. [26][27][28] This resulted in the glycosylated aromatic ketone 3 in a modest yield of 40-50%.…”