Concise, diastereoconvergent synthesis of endiandric-type tetracycles by iterative cross coupling

Both fused and bridged tetracyclic scaffolds characteristic of endiandric acid-type natural products have been prepared in just seven steps each (longest linear sequence) from Burke's commercial cis-2-bromovinylboronic acid MIDA ester. Three iterative Suzuki-Miyaura couplings using MIDA boronates, including the first such example of a Z-Z coupling, trigger an 8 pi/6 pi-electrocyclization cascade. The mixture of endo and exo bicycles thus formed are elaborated into tetracycles via Horner-Wadsworth-Emmons and Diels-Alder reactions. In the process, the endo and exo diastereomers interconvert to ultimately deliver the desired products. (C) 2016 Elsevier Ltd. All rights reserved.