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