Electrosynthesis in flow reactors. Part 1: Anodic deprotection of nitrogen containing compounds. Part 2: Cathodic cyclisation of aryl halides

Abstract

Flow electrosynthesis is an important field of chemistry, with the ability to deliver improved selectivity, higher yields, and higher productivities compared to both batch electrochemistry and chemical oxidative and reductive processes, in a manner that satisfies the global need for sustainable production of materials. Herein discusses the flow electrosynthesis carried out using a spiral, extended channel length microflow cell designed for routine and convenient application in an organic synthesis laboratory: The Ammonite 8 reactor. Specifically, two chemical transformations were explored in this work: the anodic deprotection of the 4-methoxybenzyl (PMB) protecting group from nitrogen containing compounds, and the cathodic cyclisation of aryl halides. By the anodic process, the PMB group was successfully removed from seventeen substrates, including two biologically active b lactams, with yields of up to 91%. The process could be scaled to operate in the Ammonite 15 reactor, where productivities of 43 mmol/hour could be achieved. As a continuation to this work, in collaboration with Dr Ana Folgueiras, a paired electrosynthesis was implemented using an oxidatively and reductively active molecule, 2-Iodo-N- (4-methoxybenzyl)benzamide in a parallel-plate divided electrolysis reactor developed in-house. Selective anodic removal of the PMB group, and cathodic dehalogenation of the aryl iodide were achieved, and the methodology was extended to further substrates. By the cathodic process, heterocycles were furnished from their respective aryl iodides, bromides and chlorides in what is the first metal-free mediated reductive electrosynthesis of its kind. Thirteen substrates were cyclised successfully, in yields of up to 92% and productivities of 12 mmol/hour. The mediator used to induce cyclisation was found to operate catalytically, further providing merit to the sustainability criteria of the process.

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ORCID for Richard Brown: orcid.org/0000-0003-0156-7087

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