A mild route to alpha-alkoxyacetylenes mediated by Lewis acids and synthetic routes to 10-, 11-, and 12-membered ring enediyne carbocycles

The condensation of silyl substituted acetylenes with dimethoxy acetals via a modified "Mukaiyama-type reaction" to afford alpha -alkoxyacetylenes is described. These propargylic ethers 17-21 were synthesized from the reactio n of aluminum or zinc acetylides with acetals mediated by Lewis acids. In a ppropriate cases, when a second acetal was present in the initial acyclic p roduct (24), a subsequent intramolecular acetal-ene (Prins) cyclization ens ued to afford the silylalkylidenealkoxycyclopentane (25). Enediyne species were unreactive under these conditions, even in an intramolecular case. Rou tes to 11- and 12-membered carbocyclic enediyne compounds (43, 44) were dev eloped via an intramolecular pinacol coupling of the dialdehydes 39 with sa mmarium diodide/HMPA. The requisite double bond was introduced using the th iocarbonate expulsion method with trimethyl phosphite. A route to the highl y substituted 10-membered ring enediyne 50 is also described based on the u se of an isopropylidene acetal tether control group to facilitate an intram olecular chromium (II)/nickel (II)-mediated coupling of the iodoacetylene a ldehyde 49.