Phospha-Michael Reaction on 4H-Chromen-4-one: A Useful Application for the Synthesis of Phosphorated 4-Oxochromanes, 4-Hydroxychromanes, and 4-Oxo-4H-chromenes

Abstract

We report here a practical method for the synthesis of dimethyl (4-oxochroman-2-yl)phosphonate and ethyl (4-oxochroman-2-yl)phenylphosphinate through regioselective phospha-Michael addition on chromone followed by the first high diastereoselective reduction with NaBH₄ to obtain the novel dimethyl cis-(4-hidroxychroman-2-yl)phosphonate and ethyl cis-(4-hidroxychroman-2-yl)phenylphosphinate, which using the Mitsunobu reaction were converted into trans diastereoisomers. Additionally, dimethyl (4-oxo-chroman-2-yl)phosphonate and ethyl (4-oxochroman-2-yl)phenylphosphinate were transformed into (4-oxo-4H-chromen-2-yl)phosphonic acid and (4-oxo-4H-chromen-2-yl)phenylphosphinic acid, analogues of 4-oxo-4H-chromene-2-carboxylic acid.

Keywords

4H-Chromen-4-one - Heterocyclic phosphonates - Heterocyclic phosphinates - 1,4-Addition - Diastereoselective reduction - Mitsunobu reaction

Publikationsverlauf

Eingereicht: 03. Juli 2025

Angenommen nach Revision: 18. August 2025

Accepted Manuscript online:
18. August 2025

Artikel online veröffentlicht:
01. Oktober 2025

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