A general strategy for the convergent synthesis of fused polycyclic ethers via B-alkyl Suzuki coupling: Synthesis of the ABCD ring fragment of ciguatoxins

A new method for convergent coupling of fused polycyclic ethers has been developed, which relies on B-alkyl Suzuki crosscoupling 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.