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. 2024 Nov 15;89(22):16865-16872.
doi: 10.1021/acs.joc.4c02244. Epub 2024 Nov 3.

Three-Component 1,2-Dioxygenation of 1,3-Dienes Using Carboxylic Acids and TEMPO

Sophia M Baldassarre  1 , Heidi S Sato  1 , Adam P Louise  1 , Layna L Summer  1 , Benjamin P Wilson  1 , Brett N Hemric  1
Affiliations

Three-Component 1,2-Dioxygenation of 1,3-Dienes Using Carboxylic Acids and TEMPO

Sophia M Baldassarre et al. J Org Chem. .

Abstract

A mild, metal-free 1,2-dioxygenation of 1,3-dienes using TEMPO and carboxylic acids is reported. This method includes examples for a variety of 1,3-dienes as well as aliphatic and aromatic carboxylic acids. This reaction also demonstrates complete site- and regioselectivity in the oxygen addition. Furthermore, extensive derivatization of the differential oxygen groups in the product has been demonstrated, including reduction of the remaining alkene to access alkyl, vicinally dioxygenated scaffolds. Finally, this reaction is shown both experimentally and computationally to occur through carboxylic acid-driven disproportionation of TEMPO.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Challenges in Selectivity with the 1,2-Difunctionalization of 1,3-Dienes
Scheme 2
Scheme 2. Methods for the 1,2-Dioxygenation of 1,3-Dienes
Scheme 3
Scheme 3. Competition of 1,3-Dienes and Alkenesa
Isolated yields on a 0.1 mmol scale. Isolated as a 1:9.7 mixture. ND = not detected by 1H NMR. [T] = 2,2,6,6-tetramethylpiperidine.
Scheme 4
Scheme 4. Derivatization of the Product Scaffold
Isolated yields on a 0.05 mmol scale.
Scheme 5
Scheme 5. TEMPO Oxidation
Scheme 6
Scheme 6. Mechanism for the 1,2-Dioxygenation of 1,3-Dienes through TEMPO Disproportionation (A) or Radical (B) Pathways
Scheme 7
Scheme 7. Insights into the Mechanism of the 1,2-Dioxygenation of 1,3-Dienes
ND = not detected by 1H NMR. Isolated yields on a 0.1 mmol scale.
Scheme 8
Scheme 8. Reactions and Calculated ΔG Values in DCE for the Disproportionation (A) and Radical (B) Mechanisms
Figure 1
Figure 1
Molecular orbitals relevant to the proposed mechanism. (A) SOMO for TEMPO (3a), (B) SOMO for TEMPOH+ radical (i), and (C) LUMO for TEMPO+ (ii).
See this image and copyright information in PMC

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