LeGrande M. Slaughter

Two series of sterically encumbered gold(I)-acyclic diaminocarbene (ADC) complexes were prepared by reaction of mono- and dialkylamines with gold-bound 2-mesitylphenyl isocyanide (monomesityl series) and 2,6-dimesitylphenyl isocyanide (dimesityl series). X-ray crystal structures and solution 1H NMR data showed that the ADC-gold complexes adopt major rotameric conformations with the bulky biaryl/terphenyl group and one alkyl group located syn to gold. This engenders substantial steric hindrance at the metal, as evidenced by percent buried volume (%Vbur) parameters of 35.7 – 37.2 for the monomesityl series and 46.4 – 52.4 for the dimesityl series. Modest out-of-plane distortions of the ADC N-substituents in the dimesityl series were attributed to attractive CH···π interactions between alkyl groups and mesityl rings on the basis of dispersion-corrected density functional theory calculations. Gold-catalyzed regiodivergent domino cyclization/hydroarylation reactions of a 1,6-enyne with indole revealed that the bulky biaryl/terphenyl substituents of the ligands exert a strong influence on product selectivity, with the bulkier dimesityl ADC-Au catalysts inducing a shift away from the cyclopropane-fused product toward the normally disfavored alkene product. Incorporation of a yet bulkier bis(2,6-diisopropylphenyl)-substituted terphenyl moiety into the ADC led to a gold catalyst that provided exclusive selectivity for the alkene product. Computational modeling suggested that bulky terphenyl groups hinder attack at the a carbon in the initially formed organogold intermediate, allowing steric effects to override the intrinsic electronic preference for the cyclopropane product.

Gold(I) catalyzes domino homodimerization of o-alkynylbenzaldehydes via a sequence of 6-endo-dig-cyclization, amine addition, and [4+2] cycloaddition involving two bicyclic intermediates. The resulting products integrate medicinally relevant 1,2-dihydronaphthalene and isochromene moieties into a single amine-substituted tetracyclic framework.

A Pd(OAc) ₂ /xantphos catalyst system can be tuned to promote either amination or C–H arylation of hindered binaphthyl 2-triflates, with xantphos's hemilability playing a key role.

Binding of an imino-N-heterocyclic carbene to tetrabenzylhafnium triggers complete removal of the carbene carbon via three successive benzyl migrations.

Gold-promoted cyclizations of 2,2-diaryl substituted γ-allenoic acids were found to give three isomeric lactone products, each of which could be obtained selectively by exploiting Brønsted acid/base and ligand effects. Simple 5-exo-trig cyclization products were favored by strong donor ligands or base additives, whereas weak donor ligands and a Brønsted acid additive gave isomeric enelactones resulting from double bond migration. Further optimization afforded a class of medicinally relevant bridged tricyclic lactones via a tandem hydroacyloxylation/hydroarylation process. Kinetic studies and control experiments indicated that the initial 5-exo-trig cyclization product serves as a branch point for further isomerization to the other lactone products via cooperative gold(I)/Brønsted acid catalysis.

Two complementary Kumada coupling methods for the conversion of monotriflated 1,1′-binaphthalene-2,2′-diol (BINOL) into 2′-substituted binaphthyl monoalcohols under mild conditions are reported. A protocol using NiCl₂(dppe), in combination with an improved preparation of the monotriflate, is effective for 1,1′-binaphthalene-2-ols containing unsubstituted or electron-poor aryl or benzyl 2′-substituents. An alternative procedure, using a potentially hemilabile-bidentate phosphinan-4-ol ligand, is superior for products containing neopentyl or electron-rich aryl 2′-substituents. The obtained binaphthyl alcohols represent potentially useful synthons for chiral ligands and auxiliaries.