4570-11-0

4-Acetyltropolone is derived from hinokitiol (β-thujaplicin) in four steps, with an overall yield of 60percent, via readily available 8-azidohinokitiol. γ-Thujaplicin almost quantitatively forms its difluoroboron complex, which, upon bromination, provides an 85percent yield of the 8-bromo-γ-thujaplicin difluoroboron complex.This bromo compound readily gives γ-dolabrin (87percent with triethylamine) and 8-azido-γ-thujaplicin (88percent with sodium azide), from which 5-acetyltropolone is derived in an 80percent yield by ozonolysis or in 40percent yield with sulfuric acid.The considerable differences in the reactivities observed between these 4- and 5-substituted tropolones are discussed.The pKa values of 4- and 5-acetyltropolone and 4- and 5-(3,4,5-trimethoxycinnamoyl)tropolones are also reported.

The bromotropolones (4), (5) and (10) undergo palladium-mediated cross coupling with a wide range of organostannanes to produce alkenyl-, alkyl- and aryl-substituted tropolones.The methodology has been applied to the synthesis of the monoterpenes β-dolabrin (11), β-thujaplicin (12), 4-isopropyl-7-methoxytropolone (13) and β-thujaplicinol (14).Cross coupling of bromotropolones (4), (5) and (10) with various aryltrimethylstannanes or arylboronic acids has permitted the preparation of the bicyclic colchicine analogues (30)-(43) which have been tested for tubulin-binding activity.The X-ray crystal structure of the most active of these systems, compound (38), is reported.

The bromotropolones (1), (2), and (3) cross-couple with organostannanes in the presence of palladium(O) to produce alkyl, alkenyl, or aryl substituted tropolones; the methodology has been applied to the synthesis of the monoterpenes β-dolabrin (4), β-thujaplicin (5), 7-methoxy-4-isopropyltropolone (7), and β-thujaplicinol (8).