Photochemical Ring-Expansion of Pyridines to Azepines

Abstract

The synthesis of 4H-azepine 163 is reported in 36% yield through photochemical ring-expansion by one carbon from ring-closed lithiated enolate 154 at 385 nm irradiation.
The photochemistry of lithiated enolates 168 and 178 were also carried out at 385 nm
irradiation and 365 nm irradiation respectively to see if they could photochemically ring-expand into azepines. Instead, rearomatised 170 and 179 were formed.

N-benzylpicolinamides 182 and 188 were also studied to see if they could photochemically
ring-expand into azepines at 450 nm irradiation, which only returned their respective starting
materials 182 and 188.

There is evidence that n-BuLi may behave as a nucleophile on some pyridyl substrates, where
an alternative lithiated enolate was generated from n-BuLi adding at the 4-position of the
aromatic ring in 153 that could then undergo photochemistry when irradiated at 385 nm,
forming 164 in a 15% yield. Compound 164 was racemic and isolated as a single diastereomer.

Studying the photochemistry of alternative lithiated enolates further by using n-BuLi as a
nucleophile on achiral 201 and chiral 202, displayed that n-BuLi is favoured to add at the 4-
position on the aromatic ring.

Date of Award	18 Mar 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Jonathan Clayden (Supervisor)