Belén Rubial

A practically simple and direct α-alkylation of unactivated ketones using benzylic alcohols has been achieved. The in situ formed acetals are the key for the success of the reaction. The catalyst, silver hexafluoroantimonate(V) (AgSbF₆) provides double activation by converting the ketone into an enol ether via acetal and generation of carbocationic center at the benzylic position of the benzylic alcohol. The alcohols include benzylic propargyl alcohols, cinnamyl alcohols, and diarylmethanols.

Mixtures of [{PCy₂(o-biphenyl)}AuCl] and AgSbF₆ catalyze the tandem cycloaddition/hydroarylation of 7-aryl-1,6-enynes with electron-rich arenes to form 6,6-diarylbicyclo[3.2.0]heptanes in good yield under mild conditions. Experimental observations point to a mechanism involving gold-catalyzed cycloaddition followed by silver-catalyzed hydroarylation of a bicyclo[3.2.0]hept-1(7)-ene intermediate.

Gold first, silver second: Mixtures of [{PCy₂(o-biphenyl)}AuCl] and AgSbF₆ catalyze the tandem cycloaddition/hydroarylation of 7-aryl-1,6-enynes with electron-rich arenes to form 6,6-diarylbicyclo[3.2.0]heptanes in good yield under mild conditions. Experimental observations point to a mechanism involving a gold-catalyzed cycloaddition followed by a silver-catalyzed hydroarylation of the bicyclo[3.2.0]hept-1(7)-ene intermediate.

A method for the diastereoselective carboboration of 1,2-disubstituted styrenes with aryl/vinyl bromides and (Bpin)₂ is reported. High diastereoselectivities and yields are observed for the formation of either diastereomer of the product from a single alkene isomer. These reactions provide access to a diverse range of structures from simple starting materials.

The diastereoselective carboboration of 1,2-disubstituted styrenes with aryl/vinyl bromides and (Bpin)₂ proceeds with high diastereoselectivities and yields. The formation of either diastereomer of the product from a single alkene isomer is determined by the reaction conditions. The method thus provides access to a diverse range of structures from simple starting materials.

A new synthetic strategy was devised leading to the formation of complexes, such as [Au(IPr)(CH₂COCH₃)]. The approach capitalizes on the formation of a decomposition product observed in the course of the synthesis of [Au(IPr)(Cl)]. A library of gold acetonyl complexes containing the most common N-heterocyclic carbene (NHC) ligands has been synthesized. These acetonyl complexes are good synthons for the preparation of numerous organogold complexes. Moreover, they have proven to be precatalysts in common gold(I)-catalyzed reactions.

Organogold: A library of [Au(NHC)(acetonyl)] complexes (NHC=N-heterocyclic carbene) has been easily synthesized. These complexes represent valuable synthetic precursors to a plethora of organogold species, as well as active catalysts for gold(I)-catalyzed reactions (see scheme).

Various haloalkynes are converted in the presence of a dual activation gold catalyst. Via a dual activation process a completely atom economic head-to-tail coupling delivers gem-dihalogenated conjugated enynes as valuable building blocks for organic synthesis.

Various haloalkynes are converted in the presence of a dual-activation gold catalyst. Through a dual activation process, a completely atom-economic head-to-tail coupling delivers gem- dihalogenated conjugated enynes as valuable building blocks for organic synthesis.

A gold-catalyzed intramolecular cycloisomerization of α-yne-furans 1 is described in this contribution. A variety of cyclic α,β-unsaturated aldehyde or ketone derivatives and nitrogen-containing tricyclic adducts were obtained selectively in moderate to excellent yields under mild conditions by varying the substituents on the standard substrates.

Going for gold: A variety of cyclic α,β-unsaturated aldehyde or ketone derivatives and tricyclic adducts were obtained selectively through a gold-catalyzed intramolecular reaction of propargylic esters with furan rings (see scheme). Several interesting transformations of the products are also reported.

A scalable, high yielding, rapid route to access an array of nitriles from aldehydes mediated by an oxoammonium salt (4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and hexamethyldisilazane (HMDS) as an ammonia surrogate has been developed. The reaction likely involves two distinct chemical transformations: reversible silyl-imine formation between HMDS and an aldehyde, followed by oxidation mediated by the oxoammonium salt and desilylation to furnish a nitrile. The spent oxidant can be easily recovered and used to regenerate the oxoammonium salt oxidant.

A serendipitous find: The scalable and high yielding title reaction is mediated by 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate and hexamethyldisilazane (HMDS). The reaction likely involves reversible silyl-imine formation between HMDS and an aldehyde, and subsequent oxidation and desilylation. The spent oxidant can be easily recycled.

A direct organocatalytic carbonyl/olefin oxo-metathesis has been developed. The reaction is catalyzed by trityl tetrafluoroborate (TrBF₄) and utilizes unactivated alkenes for the olefination of aromatic aldehydes to give trans β-alkylstyrenes in yields of 44–85 % with only acetone as the byproduct. The pronounced Lewis acidity of the carbocation results in unusual reactivity that is proposed to catalyze a stepwise [2+2] cycloaddition to give an oxetane intermediate. Fragmentation of the latter in a formal retro [2+2] reaction gives the oxo-metathesis product.

A new partner in the metathesis dance: Trityl tetrafluoroborate (TrBF₄) catalyzes the direct oxo-metathesis of aldehydes and unactivated olefins to give β-alkylstyrene derivatives and acetone through an unusual metal-free formal [2+2]/retro [2+2] reaction sequence.

Aromatic diyne systems bearing one terminal propargylic acetate moiety and one tertiary propargylic alcohol subunit were converted in the presence of a gold catalyst. After an initial 1,2-migration of the acetoxy group at the terminal alkyne, a gold carbenoid is formed which is then transferred onto the internal alkyne of the propargylic alcohol. This combination enables the use of propargylic acetates as precursors for a gold-catalyzed pinacol-type rearrangement. In the final pinacol-like step the shift of an alkyl or aryl moiety onto an electrophilic gold carbenoid/cation terminates the reaction and 1-naphthyl ketones are obtained as products. If electron-rich aromatic backbones are used, a mechanistically interesting alternative pathway including a retro-Buchner reaction is opened.

1,5-Diynes bearing halogen-substituted alkynes were synthesized and converted in the presence of a gold catalyst. In contrast to the corresponding hydroarylating aromatization reaction with terminal alkynes, a totally different reaction mode was observed. Instead of the expected dual catalysis pathway, only one gold center is needed and a 1,2-halogen migration is initiated in which either a gold vinylidene species or a gold carbenoid is involved. By the incorporation of one solvent molecule, diiodinated aromatic products are obtained in high selectivity.

One class of potential Lewis acids that has received negligible attention as a catalyst is the carbocation. Here we show the potential of triarylmethylium ions as highly powerful Lewis acid catalysts for organic reactions. The Lewis acidity of the triarylmethylium ion can be easily tuned by variation of the electronic properties of the aromatic rings and the catalytic activity of the carbocation is shown to correlate directly to the level of stabilization of the empty p_C-orbital at the cationic carbon. The versatility of triarylmethylium ions as efficient Lewis acid catalysts for organic reactions is demonstrated in Diels–Alder, aza-Diels–Alder, conjugate addition, halogenation, epoxide rearrangement and intramolecular hetro-ene reactions.

Modulating the diastereoselectivity of stereochemically complex molecules in asymmetric synthesis remains a challenge, especially when the reaction cycle produces no net change in the catalysts, ligands, substrates or additives. Here we accomplish a controlled diastereodivergence in the asymmetric synthesis of fully functionalized tetrahydropyrans by adjusting the sequence of an organocatalytic cascade reaction. We also show that this one-pot operation provides two synthetically important architectures with excellent stereocontrol. To the best of our knowledge, this is the first published kinetic resolution of MBH alcohols in an organocascade.

Chiral complexes formed by privileged phosphoramidites and silver triflate or silver benzoate are excellent catalysts for the general 1,3-dipolar cycloaddition between azomethine ylides generated from α-amino acid-derived imino esters and nitroalkenes affording with high dr the exo-cycloadducts 4,5-trans-2,5-cis-4-nitroprolinates in high ee at room temperature. In general, better results are obtained using silver rather than copper(II) complexes. In many cases the exo-cycloadducts can be obtained in enantiomerically pure form just after simple recrystallization. The mechanism and the justification of the experimentally observed stereodiscrimination of the process are supported by DFT calculations. These enantiomerically enriched exo-nitroprolinates can be used as reagents for the synthesis of nitropiperidines, by ester reduction and ring expansion, which are inhibitors of farnesyltransferase.