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

Mandigma, Mark John P. and Žurauskas, Jonas and MacGregor, Callum I. and Edwards, Lee J. and Shahin, Ahmed and d'Heureuse, Ludwig and Yip, Philip and Birch, David J. S. and Gruber, Thomas and Heilmann, Jörg and John, Matthew P. and Barham, Joshua P. (2022) An organophotocatalytic late-stage N–CH3 oxidation of trialkylamines to N-formamides with O2 in continuous flow. Chemical Science, 13 (7). pp. 1912-1924. ISSN 2041-6520 (https://doi.org/10.1039/d1sc05840a)

[thumbnail of Mandigma-etal-CS-2021-An-organophotocatalytic-late-stage-N-CH3-oxidation-of-trialkylamines]
Preview
Text. Filename: Mandigma_etal_CS_2021_An_organophotocatalytic_late_stage_N_CH3_oxidation_of_trialkylamines.pdf
Final Published Version
License: Creative Commons Attribution 3.0 logo

Download (2MB)| Preview

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.

ORCID iDs

Mandigma, Mark John P., Žurauskas, Jonas, MacGregor, Callum I., Edwards, Lee J., Shahin, Ahmed, d'Heureuse, Ludwig, Yip, Philip ORCID logoORCID: https://orcid.org/0000-0003-2725-7474, Birch, David J. S. ORCID logoORCID: https://orcid.org/0000-0001-6400-1270, Gruber, Thomas, Heilmann, Jörg, John, Matthew P. and Barham, Joshua P.;