The Palladium-Mediated Cross Coupling of Bromotropolones With Organostannanes or Arylboronic Acids: Applications to the Synthesis of Natural Products and Natural Product Analogs

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 ß- dolabrin (11),ß- thujaplicin (12), 4-isopropyl-7-methoxytropolone (13) and ß- 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.