Synthesis of skipped enynes via phosphine-promoted couplings of propargylcopper reagents

Ladder Polyether Synthesis via Epoxide-Opening Cascades Directed by a Disappearing Trimethylsilyl Group

“…We began our program directed toward the rapid assembly of trans -fused polyether natural products by way of epoxide-opening cascades using methods that we had previously developed for a related stepwise, or iterative, synthesis of polytetrahydropyrans 15. This strategy had four basic design elements: 1.…”

“…Toward this end, a three-carbon homologation that we had previously developed was used to prepare enyne 18 , which was then subjected to Shi asymmetric epoxidation (Scheme 2). 15a The epoxide product was not easily separated from the ketone catalyst, and thus preliminary studies were performed on the mixture. The low yield of this two-step process is attributed to the loss of material to C-H oxidation of the primary alcohol.…”

“…Similarly, triene 27 was available using the direct coupling of an alkenyl cuprate derived from hydroalumination/transmetallation of alkyne 20 ,16c with dienyl mesylate 34 15b (Scheme 6). …”

“…Building upon our results from the regioselective cyclization of monoepoxysilanes, we turned our attention toward cascades (more than one epoxide per substrate) under similar conditions 15a. Simply put, the incorporation of even just one additional epoxide complicated significantly the outcome under similar reaction conditions.…”

“…Mechanistic insight into how these products could be produced proved instrumental in our understanding of the behavior of epoxysilanes. In the case of diepoxide 36 , a bisfuran ( 37 ) was formed, a puzzling result in light of the 6- endo regioselectivity observed in the acid-mediated cyclizations of monoepoxysilanes 15a. In order to arrive at a bistetrahydrofuran, the two epoxysilanes must be opened, regioselectively, in the contrary 5- exo fashion (Figure 10, A ).…”