Diego Benitez

A bonding model for gold(I) carbene complexes

The last decade has witnessed dramatic growth in the number of reactions catalyzed by electrophilic gold complexes. While proposed mechanisms often invoke the intermediacy of gold-stabilized cationic species, the nature of bonding in these intermediates remains unclear. Herein, we propose that the carbon-gold bond in these intermediates is comprised of varying degrees of both σ and π-bonding; however, the overall bond order is generally less than or equal to unity. The bonding in a given gold-stabilized intermediate, and the position of this intermediate on a continuum ranging from gold-stabilized singlet carbene to gold-coordinated carbocation, is dictated by the carbene substituents and the ancillary ligand. Experiments show that the correlation between bonding and reactivity is reflected in the yield of gold-catalyzed cyclopropanation reactions.

Phosphine-Catalyzed Annulations of Azomethine Imines: Allene-Dependent [3 + 2], [3 + 3], [4 + 3], and [3 + 2 + 3] Pathways

In this paper we describe the phosphine-catalyzed [3 + 2], [3 + 3], [4 + 3], and [3 + 2 + 3] annulations of azomethine imines and allenoates. These processes mark the first use of azomethine imines in nucleophilic phosphine catalysis, producing dinitrogen-fused heterocycles, including tetrahydropyrazolo-pyrazolones, -pyridazinones, -diazepinones, and -diazocinones. Counting the two different reaction modes in the [3 + 3] cyclizations, there are five distinct reaction pathways-the choice of which depends on the structure and chemical properties of the allenoate. All reactions are operationally simple and proceed smoothly under mild reaction conditions, affording a broad range of 1,2-dinitrogen-containing heterocycles in moderate to excellent yields. A zwitterionic intermediate formed from a phosphine and two molecules of ethyl 2,3-butadienoate acted as a 1,5-dipole in the annulations of azomethine imines, leading to the [3 + 2 + 3] tetrahydropyrazolo-diazocinone products. The incorporation of two molecules of an allenoate into an eight-membered-ring product represents a new application of this versatile class of molecules in nucleophilic phosphine catalysis. The salient features of this protocol--the facile access to a diverse range of nitrogen-containing heterocycles and the simple preparation of azomethine imine substrates--suggest that it might find extensive applications in heterocycle synthesis.

Bimetallic Reductive Elimination from Dinuclear Pd(III) Complexes

In 2009, we reported C-halogen reductive elimination reactions from dinuclear Pd(III) complexes and implicated dinuclear intermediates in Pd(OAc)(2)-catalyzed C-H oxidation chemistry. Herein, we report results of a thorough experimental and theoretical investigation of the mechanism of reductive elimination from such dinuclear Pd(III) complexes, which establish the role of each metal during reductive elimination. Our results implicate reductive elimination from a complex in which the dinuclear core is intact and suggest that redox synergy between the two metals is responsible for the facile reductive elimination reactions observed.

Radically enhanced molecular recognition

The tendency for viologen radical cations to dimerize has been harnessed to establish a recognition motif based on their ability to form extremely strong inclusion complexes with cyclobis(paraquat-p-phenylene) in its diradical dicationic redox state. This previously unreported complex involving three bipyridinium cation radicals increases the versatility of host-guest chemistry, extending its practice beyond the traditional reliance on neutral and charged guests and hosts. In particular, transporting the concept of radical dimerization into the field of mechanically interlocked molecules introduces a higher level of control within molecular switches and machines. Herein, we report that bistable and tristable [2]rotaxanes can be switched by altering electrochemical potentials. In a tristable [2]rotaxane composed of a cyclobis(paraquat-p-phenylene) ring and a dumbbell with tetrathiafulvalene, dioxynaphthalene and bipyridinium recognition sites, the position of the ring can be switched. On oxidation, it moves from the tetrathiafulvalene to the dioxynaphthalene, and on reduction, to the bipyridinium radical cation, provided the ring is also reduced simultaneously to the diradical dication.

An acid-base-controllable [c2]daisy chain.

Artificial molecular-based muscles, which can convert chemical, electrochemical, or photochemical energy into mechanical motion, have attracted attention as a result of their potential for spawning nanoelectromechanical systems (NEMS). Several materials, such as conducting polymers, single-walled carbon nanotubes, and dielectric elastomers, have been developed which exhibit muscle-like behavior at the nanoscale level. However, all these systems rely upon the response of a bulk substance, rather than on the behavior of individual molecules. Recently, artificial muscles have been designed on a molecular scale by taking advantage of conformational changes exerted by electrochemical stimuli. For example, oligothiophene-calix[4]arene copolymers and thiophene-fused annulenes exhibit molecular actuating behavior under redox control while crown-etherannelated oligothiophenes and polyheterocyclic strands have ion-triggered muscle-like properties. Nanoscale molecular motions, based on artificial molecular machines, offer alternative opportunities to design artificial muscle-like materials. Bistable rotaxanes are a promising component for such materials, because relative linear mechanical translocation of the ring and dumbbell components can be achieved upon activation by chemical, electrical, or light irradiation stimuli. Converting such internal molecular motions into practical actuating materials requires relocating these internal motions into components, which, when taken together, exhibit linear expansion and contraction. Sauvage et al. have reported a linear molecular muscle, based on a transition-metal templated, doubly threaded rotaxane, which can undergo the required expansion and contraction motions on the addition or removal of metal ions. On the other hand, we have reported a switchable, palindromically constituted, doubly bistable [3]rotaxane which can be selfassembled onto gold-coated microcantilevers with disulfideterminated tethers emanating from its two rings in such a manner that they can be moved towards and away from each other under redox control. Controllable and reversible deflection of the microcantilevers can be achieved when the integrated system is exposed to the addition of oxidants or reductants (or subjected to oxidizing or reducing electrochemical potentials). Acid–base controllable, bistable, rotaxane-based molecular shuttles have been reported in which a dibenzo[24]crown-8 (DB24C8) ring switches under acid–base control between two different recognition sites on a dumbbell component, where one of the sites is a secondary dialkylammonium (R2NH2 ) center and the other site, an N,N’dialkylated-4,4’-bipyridinium (Bpym) unit. Although this switching has subsequently been employed in the design of more complex machines, such as nanoscale elevators, the mechanical motions are still only relative internal movements, that is to say, there is no contraction/expansion in their overall molecular dimensions. Herein, a bistable molecular architecture incorporating a two-component [c2]daisy chain topology is designed and synthesized (Scheme 1), wherein two mechanically interlocked filaments glide along one another through the terminal crown ether rings and in which the end of each filament is attached to bulky stoppers to prevent

Gold-Catalyzed Intramolecular Aminoarylation of Alkenes: C-C Bond Formation through Bimolecular Reductive Elimination

Gold-ilocks and the 3 mol % catalyst: Bimetallic gold bromides allow the room temperature aminoarylation of unactivated terminal olefins with aryl boronic acids using Selectfluor as an oxidant. A catalytic cycle involving gold(I)/gold(III) and a bimolecular reductive elimination for the key CC bond-forming step is proposed. dppm= bis(diphenylphosphanyl)methane.

Two Metals Are Better Than One in the Gold Catalyzed Oxidative Heteroarylation of Alkenes

We present a detailed study of the mechanism for oxidative heteroarylation, based on DFT calculations and experimental observations. We propose binuclear Au(II)-Au(II) complexes to be key intermediates in the mechanism for gold catalyzed oxidative heteroarylation. The reaction is thought to proceed via a gold redox cycle involving initial oxidation of Au(I) to binuclear Au(II)-Au(II) complexes by Selectfluor, followed by heteroauration and reductive elimination. While it is tempting to invoke a transmetalation/reductive elimination mechanism similar to that proposed for other transition metal complexes, experimental and DFT studies suggest that the key C-C bond forming reaction occurs via a bimolecular reductive elimination process (devoid of transmetalation). In addition, the stereochemistry of the elimination step was determined experimentally to proceed with complete retention. Ligand and halide effects played an important role in the development and optimization of the catalyst; our data provides an explanation for the ligand effects observed experimentally, useful for future catalyst development. Cyclic voltammetry data is presented that supports redox synergy of the Au···Au aurophilic interaction. The monometallic reductive elimination from mononuclear Au(III) complexes is also studied from which we can predict a ~15 kcal/mol advantage for bimetallic reductive elimination.

Alkylgold complexes by the intramolecular aminoauration of unactivated alkenes

Alkylgold(I) complexes were formed from the gold(I)-promoted intramolecular addition of various amine nucleophiles to alkenes. These experiments provide the first direct experimental evidence for the elementary step of gold-promoted nucleophilic addition to an alkene. Deuterium-labeling studies and X-ray crystal structures provide support for a mechanism involving anti-addition of the nucleophile to a gold-activated alkene, which is verified by DFT analysis of the mechanism. Ligand studies indicate that the rate of aminoauration can be drastically increased by use of electron-poor arylphosphines, which are also shown to be favored in ligand exchange experiments. Attempts at protodeauration lead only to recovery of the starting olefins, though the gold can be removed under reducing conditions to provide the purported hydroamination products.

On the Impact of Steric and Electronic Properties of Ligands on Gold(I)-Catalyzed Cycloaddition Reactions

It is shown that [4 + 3] and [4 + 2] cycloaddition pathways are accessible in the Au(I) catalysis of allene-dienes. Seven-membered ring gold-stabilized carbenes, originating from the [4 + 3] cycloaddition process, are unstable and can rearrange via a 1,2-H or a 1,2-alkyl shift to yield six- and seven-membered products. Both steric and electronic properties of the AuL(+) catalyst affect the electronic structure of the intermediate gold-stabilized carbene and its subsequent reactivity.

Relevance of cis- and trans-dichloride Ru intermediates in Grubbs-II olefin metathesis catalysis (H2IMesCl2Ru=CHR).

Using density functional theory with the B3LYP and M06 functionals, we show conclusively that the (H(2)IMes)(Cl)(2)Ru olefin metathesis mechanism is bottom-bound with the chlorides remaining trans throughout the reaction, thus attempts to effect diastereo- and enantioselectivity should focus on manipulations that maintain the trans-dichloro Ru geometry.