A General Strategy for the Convergent Synthesis of Fused Polycyclic Ethers via B-Alkyl Suzuki Coupling: Synthesis of the ABCD Ring Fragment of Ciguatoxins.

Abstract A new method for convergent coupling of fused polycyclic ethers has been developed, which relies on B -alkyl Suzuki cross-coupling of lactone-derived enol triflates or phosphates. The strategy was successfully applied to a convergent synthesis of the ABCD ring fragment 4 of ciguatoxins, the causative toxin for ciguatera fish poisoning. The synthetic route includes a convergent union of the B and D rings ( 18 and 29c , respectively) by the B -alkyl Suzuki coupling, introduction of a double bond into the D ring followed by reductive closure of the tetrahydropyran C ring to afford the BCD ring system 51 , and, finally, ring-closing metathesis reaction to construct the oxepene A ring.