Approach toward the total synthesis of orevactaene. Part 1: Assembly of the contiguous trisubstituted olefin component

An approach to the conjugated polyene chain component of orevactaene is reported. A modular approach has been devised to link the two stereocentre-containing ends of the structure together via a tri-substituted olefin-template. Key to the success of this approach is an efficient ‘one pot’ lithium/halogen exchange, boron/lithium exchange, borate ester saponification, and cross-coupling sequence to provide two contiguous trisubstituted olefins with absolute stereo- and regiocontrol in excellent overall yield. These results have paved the way for a parallel synthesis approach to prepare all 16 possible stereoisomers of orevactaene so that the relative and absolute stereochemistry of this compound can be determined.