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[4+2] Cycloaddition Reactions Between 1,8‐Disubstituted Cyclooctatetraenes and Diazo Dienophiles: Stereoelectronic Effects, Anticancer Properties and Application to the Synthesis of 7,8‐Substituted Bicyclo[4.2.0]octa‐2,4‐dienes
Author(s) -
Grange Rebecca L.,
Gallen Michael J.,
Schill Heiko,
Johns Jenny P.,
Dong Lin,
Parsons Peter G.,
Reddell Paul W.,
Gordon Victoria A.,
Bernhardt Paul V.,
Williams Craig M.
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200903454
Subject(s) - cycloaddition , diazo , chemistry , bicyclic molecule , adduct , stereochemistry , medicinal chemistry , organic chemistry , catalysis
A detailed examination of [4+2] cycloaddition reactions between 1,8‐disubstituted cyclooctatetraenes and diazo compounds revealed that 4‐phenyl‐1,2,4‐triazole‐3,5‐dione (PTAD) reacts to form either 2,3‐ or 3,4‐disubstituted adducts. The product distribution can be controlled by modulating the electron density of the cyclooctatetraene. Unprecedented [4+2] cycloadditions between diisopropyl azodicarboxylate (DIAD) and 1,8‐disubstituted cyclooctatetraenes are also described and further manipulation of a resulting cycloadduct uncovered a new pathway to the synthetically challenging bicyclo[4.2.0]octa‐2,4‐diene family. Variation of the substituents resulted in a range of compounds displaying selective action against different human tumour cell types.