REGIOSELECTIVE SYNTHESIS OF 14-MEMBERED BIARYL ETHERS - TOTAL SYNTHESIS OF RA-VII AND DEOXYBOUVARDIN

In order to obtain a key compound (22a'') for synthesis of RA-VII (1) and deoxybouvardin (2), construction of the 14-membered ring system wa s performed by means of thallium trinitrate-mediated oxidation of the tetrahalogeno amides 5-7. The dibromo dichloro amide 6 or the bromo tr ichloro amide 7 gave a natural type of 14-membered ring dienone (23a o r 23c), whereas the tetrabromo amide 5 gave an unnatural type of produ ct, 19a. The formation of the latter product 19a could be understood o n the basis of energy calculations on plausible intermediates 26a-c an d 27a-c in the transition state in the oxidaive coupling reaction. Com pound 23a was further converted to 22a'' through conventional procedur es (aromatization; methylation; catalytic hydrogenation). This interme diate was readily converted to 1 and 2, Thus, total synthesis of RA-VI I (1) and deoxybouvardin (2) was achieved for the first time.