Nitrogen-directed free radical rearrangements

Thesis



This thesis describes efforts to develop new methods for the synthesis of bridged azacycles using nitrogen-directed free radical rearrangements. Free radical addition to 7-azanorbornadienes were carried out to give 7-substituted 2- azanorbornenes (Scheme a.l, X-Y = RS-H or PhSe-H).

[illustration in text ...]

Scheme a. 1 Nitrogen-directed homoallylic radical rearrangement via intermolecular radical addition.

A conceptually novel and theoretically interesting nitrogen-directed neophyl rearrangement (Scheme a.2) was developed into a synthesis of 2- azabenzonorbornanes 2.

[illustration in text ...]

Scheme a.2 Nitrogen-directed neophyl-like rearrangement to 2-azabenzonorbornanes.

In this case the radical 1 was generated by Barton deoxygenation of 7- azabenzonorbornanols. The effect on rearrangement of bicyclic core substitution and of aromatic ring electronics was probed in some detail, and the process was synthetically useful for a wide range of substrates.

Variation of the protecting group on nitrogen was investigated and the product profiles from neophyl-like rearrangement were consistent with a process driven by the stability of a radical α to nitrogen as a result of SOMO-lone pair orbital interaction.

The kinetics and mechanism of these processes are examined where appropriate, leading to estimates of rate constants for the rearrangements.

Authors: Bebbington, M; Bebbington, M. W. P.

• Publication date: 2002
• DOI: 10.5287/ora-brrjpkxzn
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Bicyclic compounds; Free radical reactions