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. 2024 Dec 6;89(23):17635-17642.
doi: 10.1021/acs.joc.4c02389. Epub 2024 Nov 12.

Polysubstituted Pyridines from 1,4-Oxazinone Precursors

L C Thompson  1 , Adrianne M Kinsey  1 , Zannatul Shahla  1 , Jonathan R Scheerer  1
Affiliations

Polysubstituted Pyridines from 1,4-Oxazinone Precursors

L C Thompson et al. J Org Chem. .

Abstract

This study describes a general method for the preparation of 1,4-oxazin-2-one intermediates from acetylene dicarboxylate and β-amino alcohol precursors. Oxazinones prepared in this manner were employed in a tandem cycloaddition/cycloreversion reaction sequence with a model alkyne (phenyl acetylene) to give substituted pyridine products. Fundamental reactivity and selectivity studies are complemented by the synthesis of the polycyclic ergot alkaloid natural product xylanigripone A.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Diels–Alder/retro Diels–Alder sequence with 1,4-oxazinone.
Figure 2
Figure 2
Original and recent method preparing oxazinone intermediates.
Scheme 1
Scheme 1. Merged Cycloaddition, Cycloreversion, and Aldol Condensation with 2-ethynylbenzaldehyde
Scheme 2
Scheme 2. Cycloaddition and Cycloreversion with 2-Nitrophenylacetylene
Scheme 3
Scheme 3. Synthesis of Xylanigripone A
See this image and copyright information in PMC

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