A direct and stereocontrolled route to conjugated enediynes

A unified synthetic route to 3-hex-en-1,5-diynes, a key building block foun d in many of the enediyne antitumor agents and designed materials, was deve loped. The method, which relies on a carbenoid coupling-elimination strateg y is tolerant of a wide range of functionalities, and was applied to the sy nthesis of a variety of linear and cyclic enediynes. Reaction parameters ca n be adjusted to control stereoselectivity of the process, producing linear enediynes from 1:12 to >100:1 E:Z ratio, and in-the case of cyclic enediyn es, giving the exclusively Z C-9, C-10, or C-11 products. Key features of t he process are the ready availability of precursors and the mildness and ef ficiency of the reaction. Application of the process in the design of mater ials precursors and preparation of enediyne antitumor agents are presented.