Gold-catalyzed cyclization reactions of allenes

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

Gold(I)-Catalyzed Intramolecular Hydroarylation of Allenes

Gold(I) complexes react with 4-allenyl arenes in an exo fashion to furnish vinyl-substituted benzocycles. Phosphite gold(I) monocations were found to be optimal, and the catalyst was tolerant of ethers, esters, and pyrroles. Reactions proceeded in unpurified solvent at room temperature

Mechanistic Surprises in the Gold(I)-Catalyzed Intramolecular Hydroarylation of Allenes

Zwei machen die Show: Mechanistische Studien über die Cyclisierung von allenischen Arenen zeigen, dass die Ruheform des Katalysators ein zweikerniges verbrücktes Vinylsystem ist. Dieses wurde..

Gold(I)-catalyzed intermolecular hydroarylation of allenes with nucleophilic arenes: scope and limitations

The addition of nucleophilic methoxyarenes to allenes proceeds at room temperature in dichloromethane with a catalytic amount of phosphite-gold(I) precatalyst and silver additive. The addition is regioselective for the allene terminus, and generates E-allylation products without the need for prefunctionalization of the synthons as organometallics or allyl bromides. Coordinating heteroaromatics and sterically hindered allenes do not participate in the reaction

Gold(I)-Catalyzed Cascade Cyclization of Allenyl Epoxides

Cationic gold(I) phosphite catalysts activate allenes for epoxide cascade reactions. The system is tolerant of numerous functional groups (sulfones, esters, ethers, sulfonamides) and proceeds at room temperature in dichloromethane. The cyclization pathway is sensitive to the substitution pattern of the epoxide, and the backbone structure of the A-ring. It is capable of producing medium-ring ethers, fused 6-5 bicyclic, and linked pyran-furan structures. The resulting cycloisomers are reminiscent of structures found in numerous polyether natural products

Synthesis of a Novel Type of 2,3'-BIMs via Platinum-Catalysed Reaction of Indolylallenes with Indoles

Optimisation, scope and mechanism of the platinum-catalysed addition of indoles to indolylallenes is reported here to give 2,3'-BIMs with a novel core structure very relevant for pharmaceutical industry. The reaction is modulated by the electronic properties of the substituents on both indoles, with the 2,3'-BIMs favoured when electron donating groups are present. Although simple at first, a complex mechanism has been uncovered that explains the different behaviour of these systems with platinum when compared with other metals (e.g. gold). Detailed labelling studies have shown Pt-catalysed 6-endo-trig cyclisation of the indollylallene as the first step of the reaction and the involvement of two cyclic vinyl-platinum intermediates in equilibrium through a platinum carbene, as the key intermediates of the catalytic cycle towards the second nucleophilic attack and formation of the BIMs

Chirality transfer in metal-­‐catalysed intermolecular addition reactions involving allenes

Allene chemistry in the presence of transition metal complexes is nowadays a very important topic that underpins many challenges and advances in organic synthesis. The amount of research articles covering new transformations of allenes is vast and the development of enantioselective reactions involving allenes has flourished in the last 10-15 years. In this review we cover three important topics in allene chemistry that we feel are timely appropriate for this special issue celebrating the work of Prof Trost: the metal-catalysed reactions involving chirality transfer from chiral allenes to products; the analysis of the possible racemization processes that have been observed in the interaction of some metals with allenes; and the chirality transfer using racemic allenes in reactions catalysed by metal complexes bearing chiral ligands to produce enantioriched products. We have focussed the review on intermolecular addition reactions as they are still much less explored than the intramolecular version

Response to Science Magazine NextGen special issue, 20 May

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Tarselli Interview for UMass Goessmann Gazette

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