Stereodivergent Desymmetrization of Phenols En Route to Modular Access to Densely Functionalized Quinazoline and Oxazine Scaffolds

The de novo assembly of stereochemically and skeletally diverse scaffolds is a powerful tool for the discovery of novel chemotypes. Hence, the development of modular, step- and atom-economic synthetic methods to access stereochemically and skeletally diverse compound collection is particularly impor...

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Bibliographic Details
Published in:Journal of organic chemistry 2023-02, Vol.88 (3), p.1600-1612
Main Authors: Srikanth, Gourishetty, Ravi, Anil, Sebastian, Anusha, Khanfar, Monther A., Abu-Yousef, Imad A., Majdalawieh, Amin F., El-Gamal, Mohammed I., Alkubaisi, Bilal O., Shahin, Afnan I., Joseph, Jobi, Al-Tel, Taleb H.
Format: Article
Language:English
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Summary:The de novo assembly of stereochemically and skeletally diverse scaffolds is a powerful tool for the discovery of novel chemotypes. Hence, the development of modular, step- and atom-economic synthetic methods to access stereochemically and skeletally diverse compound collection is particularly important. Herein, we show a metal-free, stereodivergent build/couple/pair strategy that allows access to a unique collection of benzo­[5,6]­[1,4]­oxazino­[4,3-a]­quinazoline, quinolino­[1,2-a]­quinazoline and benzo­[b]­benzo [4,5]­imidazo­[1,2-d]­[1,4]­oxazine scaffolds with complete diastereocontrol and wide distribution of molecular architectures. This metal-free process proceeds via desymmetrization of phenol derivatives. The cascade unites Mannich with aza-Michael addition reactions, providing expeditious entries to diverse classes of molecular shapes in a single operation.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.2c02653