| Cycloisomerization is a so-called "atom-economic" tool to produce complex carbocycles from simple precursors. Gold catalysis is an extension of cation-olefin cyclization utilizing Pt2+ that had been a previous focus of our group. As a homogeneous metal catalyst, gold - especially in the (I) oxidation state - is highly carbophilic, exhibits high functional group tolerance, and is not inhibited by trace moisture or air. This combination of attributes is ideal for use of gold as a catalytic C-C bond-forming tool.;Eneallene cycloisomerization catalyzed by gold(I) yields vinylcyclohexenes in a rare example of 6-membered ring formation. However, enantioselective synthesis with gold is challenging due to the linear bonding geometries observed for gold(I) salts. A sufficiently bulky chiral di-gold complex with judicious counterion choice produces the desired vinylcyclohexene in up to 72% yield (77% ee).;Allenes tethered to an electron-rich aromatic ring in place of an alkene partner cyclize to form tetrahydronaphthalene skeletons, even at 1 mol% catalyst loading in commercial-grade solvent. This catalysis was accelerated by more electrophilic phosphite ligands, along with a larger, weakly coordinated counterion (-SbF6). Yields range from 59-94%. If the tethered arene is non-nucleophilic (Ph) or strongly deactivating ( p-NO2), selective hydration of the allene to a methyl ketone is preferred, which provides both a mechanistic rationale and a benchmark for arene nucleophilicity that correlates well with literature. More electrophilic catalyst precursors are able to catalyze the intermolecular addition of electron-rich arenes to allenes, although the scope of this transformation was significantly more limited (9 examples, 22-90% yield). This reaction does not proceed with coordinating arenes and sterically demanding allenes.;Cascade cyclization of allenyl epoxides proceeds rapidly under gold(I) catalysis to produce polyethers remniscient of those found in marine and soil polyethers. Initial attempts to cyclize simple allenyl mono- or bis-epoxides led to complex product mixtures, but use of a hydroxyl "trapping group" yields polycycles in 35-65% yield. Carbocation stability (3° > 2° > 1°) controls ring formation in the cascade; the resultant polycycles appear to be stereospecific with respect to initial epoxide geometry. The cyclization can be extended to form both fused and linked polyethers from properly-substituted polyepoxides. |
