Issue 7, 2022

An organophotocatalytic late-stage N–CH3 oxidation of trialkylamines to N-formamides with O2 in continuous flow

Abstract

We report an organophotocatalytic, N–CH3-selective oxidation of trialkylamines in continuous flow. Based on the 9,10-dicyanoanthracene (DCA) core, a new catalyst (DCAS) was designed with solubilizing groups for flow processing. This allowed O2 to be harnessed as a sustainable oxidant for late-stage photocatalytic N–CH3 oxidations of complex natural products and active pharmaceutical ingredients bearing functional groups not tolerated by previous methods. The organophotocatalytic gas–liquid flow process affords cleaner reactions than in batch mode, in short residence times of 13.5 min and productivities of up to 0.65 g per day. Spectroscopic and computational mechanistic studies showed that catalyst derivatization not only enhanced solubility of the new catalyst compared to poorly-soluble DCA, but profoundly diverted the photocatalytic mechanism from singlet electron transfer (SET) reductive quenching with amines toward energy transfer (EnT) with O2.

Graphical abstract: An organophotocatalytic late-stage N–CH3 oxidation of trialkylamines to N-formamides with O2 in continuous flow

Supplementary files

Article information

Article type
Edge Article
Submitted
22 Okt. 2021
Accepted
26 Dec. 2021
First published
28 Dec. 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022,13, 1912-1924

An organophotocatalytic late-stage N–CH3 oxidation of trialkylamines to N-formamides with O2 in continuous flow

M. J. P. Mandigma, J. Žurauskas, C. I. MacGregor, L. J. Edwards, A. Shahin, L. d'Heureuse, P. Yip, D. J. S. Birch, T. Gruber, J. Heilmann, M. P. John and J. P. Barham, Chem. Sci., 2022, 13, 1912 DOI: 10.1039/D1SC05840A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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