Metal- and Additive-Free Synthesis of α-Hydroxyamino Ketones Enabled by Organophotocatalyst

Dedicated to Professor Masahiro Murakami on the occasion of his retirement from Kyoto University

Abstract

We report herein a straightforward method for the synthesis of α-hydroxyamino ketones, which involves the benzoylation reaction of nitrones with 2-benzoyl-2-phenylbenzothiazoline under organophotocatalysis. This method offers access to a variety α-hydroxyamino ketones without the use of any transition-metal catalyst or base. Control experiments suggested that the reaction proceeded through a benzoyl radical addition to nitrone. Benzothiazoline was found to be a more suitable radical precursor than Hantzsch ester.

Key words

hydroxyamino ketone - hydroxylamine - nitrone - benzothiazoline - organophotocatalyst - metal-free

Publication History

Received: 09 February 2023

Accepted after revision: 21 March 2023

Accepted Manuscript online:
21 March 2023

Article published online:
14 April 2023

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• 14 Example Synthetic ProcedureSequentially, nitrone 1a (0.050 mmol), benzothiazoline 2a (0.10 mmol), 4CzIPN (1 mol%), and acetonitrile (1 mL, 0.05 M) were added to a dried 20 mL test tube containing a stirrer bar. The mixture was subjected to freeze-pump-thaw process (3 cycles) and back-filled with N₂. The reaction was irradiated with white LED at rt for 14 h. After being exposed to air, the reaction mixture was concentrated and purified by preparative thin-layer chromatography on silica gel (hexane/ethyl acetate, 5:1 v/v) to give the corresponding α-hydroxyamino ketone 3a in 73% yield as a white solid. Spectral Information for Compound 3a ¹H NMR (400 MHz, CDCl₃): δ = 8.87 (dd, J = 1.3, 8.5 Hz, 2 H), 7.60 (tt, J = 0.9, 7.6 Hz, 1 H), 7.46 (dd, J = 7.7, 8.1 Hz, 2 H), 7.33–7.22 (m, 5 H), 6.08 (br s, 1 H), 4.21 (d, J = 9.0 Hz, 1 H), 4.13 (d, J = 13.4 Hz, 1 H), 3.85 (d, J = 13.4 Hz, 1 H), 2.48–2.33 (m, 1 H), 1.17 (d, J = 6.6 Hz, 3 H), 0.87 (d, J = 6.8 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 205.7, 138.4, 137.5, 133.6, 129.0, 128.7, 128.4, 128.3, 127.3, 71.6, 61.2, 29.4, 20.3, 19.8 ppm. HRMS (ESI): m/z calcd for C₁₈H₂₁NO₂Na: 306.1470; found: 306.1470.

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