10.1002/chem.201905712
Chemistry - A European Journal
COMMUNICATION
We hope this methodology will prove to be a general route to
valuable quinazolinone scaffolds.
Acknowledgements
Financial support for this work was provided by GSK via the
GSK/University of Strathclyde Centre for Doctoral Training in
Synthetic and Medicinal Chemistry. Further funding was
provided by the EPSRC via Prosperity Partnership
EP/S035990/1, who we thank. We also thank Stephen Richards
(GSK) for his assistance with NMR analysis.
Keywords: cyclisation • hydrogen transfer • iron(III) • cyanamide
• radicals
Scheme 4. Proposed mechanism of the HAT-mediated radical domino
reaction towards quinazolinones VI and structures of side-products VII–X.
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Scheme 5. Switch in ortho:para (o:p) selectivity with varying electronic groups
on the phenyl ring. Isolated yields quoted. All reactions performed on a 0.5
mmol scale using conditions from Table 1 entry 2. *Products inseparable on
silica.
In summary, we have developed HAT methodology to
enable the synthesis of (spiro)quinazolinone scaffolds from
tractable N-cyanamide alkenes (synthesised from their acid and
cyanamide counterparts). The reaction has been shown to be
scalable and has been optimised to accept challenging electron-
deficient heterocycles. An oxidative step is believed to be the
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