Decagram-scale synthesis of the neocarzinostatin carboxylic acid

Neocarzinostatin carboxylic acid (2) was synthesized on a 10g scale in 9 st eps and 43% overall yield from 3,5-dimethylanisol (9) (Schemes 5, 7). The h indered bromoarene 23, reached after 3 steps, underwent a high-temperature Heck coupling with ethyl acrylate, generating cinnamic ester 24. The C=C bo nd was reduced and the C equivalent to N group methanolized to obtain diest er 30. This underwent a regioselective Dieckmann cyclization, furnishing th e dihydronaphthalene 13, that was then aromatized. The resulting eater 31 w as carefully hydrolyzed such that the target acid 2 arose free from decarbo xylation product 32.