The key feature of the fourth-generation approach was the utilization of bidirectional fragment, vinyl iodide/phosphonium salt. phosphonium salt could be readily obtained as the trisubstituted vinyl iodide is less reactive than alkyl iodide. A Wittig reaction with followed by Suzuki coupling with alkyl iodide efficiently furnished the backbone of (+)-discodermolide. The Smith fourth-generation synthesis of (+)-discodermolide has an overall yield of 9.0% with a longest linear sequence of 17 steps and 36 total steps.