Gold-catalyzed cyclization reactions of allenes Public Deposited

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  • March 21, 2019
  • Tarselli, Michael Andrew
    • Affiliation: College of Arts and Sciences, Department of Chemistry
  • 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 Pt(II) 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.
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  • Gagne, Michel
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