A shape-persistent alleno-acetylenic macrocycle with a modifiable periphery: synthesis, chiroptical properties and H-bond-driven self-assembly into a homochiral columnar structure.

A shape-persistent alleno-acetylenic macrocycle, peripherally decorated with eight phenolic rings, has been synthesized in enantiomerically pure form. Its electronic circular dichroism spectrum features a strong chiroptical response. In the solid state, the macrocycle stacks in pillars to form channels and the stacks undergo further self-assembly into a three-dimensional porous architecture through lateral intermolecular hydrogen-bonding.

Catalytic asymmetric C-N bond formation: phosphine-catalyzed intra- and intermolecular γ-addition of nitrogen nucleophiles to allenoates and alkynoates.

Pin the amine on the gamma: A new method has been developed for the γ-addition of nitrogen nucleophiles to γ-substituted alkynoates or allenoates through intra- and intermolecular processes that are catalyzed by spirophosphine 1. An asymmetric version of this reaction affords enantioenriched pyrrolidines, indolines, and γ-amino-α,ß-unsaturated carbonyl compounds.

Modified [(IPr)Pd(R-acac)Cl] complexes: influence of the acac substitution on the catalytic activity in aryl amination.

The synthesis of a series of [(IPr)Pd(R-acac)Cl] precatalysts (acac=acetylacetonato; IPr=1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), where the acac ligand on palladium has been systematically modified through terminal substitution, is reported. The following substituted acac ligands are employed in this study: dibenzoylmethanato (dbm), benzoylacetonato (bac), tetramethylheptanedionato (tmhd), and hexafluoroacetylacetonato (hfac). Full spectroscopic characterization of the new complexes is provided along with X-ray studies for three of these. Investigation of their catalytic activity in cross-coupling is also presented through a comparative study in an aryl amination reaction. The catalytic results show a strong correlation between the increased steric bulk of the acac substituents and an increased activation rate of the precatalyst, going from the acac to the tmhd ligand. This observation, along with the inertness of the hfac compound, seems to support our previous proposal for the activation mechanism of these complexes under cross-coupling conditions.

Au/Ag-cocatalyzed aldoximes to amides rearrangement under solvent- and acid-free conditions.

The gold/silver-cocatalyzed conversion of aldoximes into primary amides is reported. The reaction, which proceeds under neat and acid-free conditions, allows for the conversion of a range of aldoximes, and is a rare example of cooperative catalysis involving well-defined gold species.

Gold- and platinum-catalyzed cycloisomerization of enynyl esters versus allenenyl esters: an experimental and theoretical study.

Ester-way to heaven: Unexpected formation of bicyclo[3.1.0]hexene 4 was the main focus of combined experimental and theoretical studies on the Au-catalyzed cycloisomerization of branched dienyne 1 (see scheme), which provided better understanding of the mechanistic details governing the cyclization of enynes bearing a propargylic ester group.Experimental and theoretical studies on Au- and Pt-catalyzed cycloisomerization of a branched dienyne with an acetate group at the propargylic position are presented. The peculiar architecture of the dienyne precursor, which has both a 1,6- and a 1,5-enyne skeleton, leads, in the presence of alkynophilic gold catalysts, to mixtures of bicyclic compounds 3, 4, and 5. Formation of unprecedented bicyclo[3.1.0]hexene 5 is the main focus of this study. The effect of the ancillary ligand on the gold center was examined and found to be crucial for formation of 5. Further mechanistic studies, involving cyclization of an enantioenriched dienyne precursor, (18)O-labeling experiments, and DFT calculations, allowed an unprecedented reaction pathway to be proposed. We show that bicyclo[3.1.0]hexene 5 is likely formed by a 1,3-OAc shift/allene-ene cyclization/1,2-OAc shift sequence, as calculated by DFT and supported by Au-catalyzed cyclization of isolated allenenyl acetate 7, which leads to improved selectivity in the formation of 5. Additionally, the possibility of OAc migration from allenyl acetates was supported by a trapping experiment with styrene that afforded the corresponding cyclopropane derivative. This unprecedented generation of a vinyl metal carbene from an allenyl ester supports a facile enynyl ester/allenenyl ester equilibrium. Further examination of the difference in reactivity between enynyl acetates and their corresponding [3,3]-rearranged allenenyl acetates toward Au- and Pt-catalyzed cycloisomerization is also presented.

[(NHC)Au(I)]-catalyzed acid-free alkyne hydration at part-per-million catalyst loadings.

A highly efficient [(NHC)Au(I)]-based (NHC = N-heterocyclic carbene) catalytic system for the hydration of an array of alkynes that operates under acid-free conditions and at very low catalyst loadings (typically 50-100 ppm and as low as 10 ppm) was developed. Terminal and internal alkynes possessing any combination of alkyl and aryl substituents (alkyl/H, aryl/H, alkyl/alkyl, alkyl/aryl, and aryl/aryl) were found suitable substrates in the present catalytic system.

Mechanism of the [(NHC)Au(I)]-catalyzed rearrangement of allylic acetates. A DFT study.

The DFT study of the mechanism of the rearrangement of H(2)C=CHC(CH(3))OCOCH(3) to (CH(3))(H)C=CHCH(2)OCOCH(3) catalyzed by [(NHC)Au](+) (NHC = N-heterocyclic carbene) shows that a low energy path exists, with a barrier of 14.2 kcal x mol(-1), going through a six-membered ring acetoxonium intermediate and where gold coordinates one of the carbon atoms in the alkene system. The qualitative features of the mechanism are not affected by the introduction of other NHC ligands, counterions, or solvation effects.

N-heterocyclic carbenes in gold catalysis.

The appealing properties of N-heterocyclic carbenes (NHC) as ancillary ligands and the high potential of gold as an organometallic catalyst have made their encounter inevitable. Still in its infancy, NHC-gold catalysis is nevertheless growing rapidly. In this tutorial review, catalytic transformations involving NHC-containing gold(I) and gold(III) complexes are presented. Particular attention is drawn to the versatility and selectivity of these catalysts.

Well-defined N-heterocyclic carbenes-palladium(II) precatalysts for cross-coupling reactions.

Metal-catalyzed cross-coupling reactions, notably those permitting C-C bond formation, have witnessed a meteoritic development and are now routinely employed as a powerful synthetic tool both in academia and in industry. In this context, palladium is arguably the most studied transition metal, and tertiary phosphines occupy a preponderant place as ancillary ligands. Seriously challenging this situation, the use of N-heterocyclic carbenes (NHCs) as alternative ligands in palladium-catalyzed cross-coupling reactions is rapidly gaining in popularity. These two-electron donor ligands combine strong sigma-donating properties with a shielding steric pattern that allows for both stabilization of the metal center and enhancement of its catalytic activity. As a result, the number of well-defined NHC-containing palladium(II) complexes is growing, and their use in coupling reactions is witnessing increasing interest. In this Account, we highlight the advantages of this family of palladium complexes and review their synthesis and applications in cross-coupling chemistry. They generally exhibit high stability, allowing for indefinite storage and easy handling. The use of well-defined complexes permits a strict control of the Pd/ligand ratio (optimally 1/1), avoiding the use of excess costly ligand that usually requires end-game removal. Furthermore, it partly removes the "black box" character often associated with cross-coupling chemistry and catalyst formation. In the present Account, four main classes of NHC-containing palladium(II) complexes will be presented: palladium dimers with bridging halogens, palladacycles, palladium acetates and acetylacetonates, and finally pi-allyl complexes. These additional ligands are best described as a protecting shell that will be discarded going from the palladium(II) precatalyst to the palladium(0) true catalyst. The synthesis of all these precatalysts generally requires simple and short synthetic procedures. Their catalytic activity in different cross-coupling reactions is discussed and put into context. Remarkably, some NHC-containing catalytic systems can achieve extremely challenging coupling reactions such as the formation of tetra-ortho-biphenyl compounds and perform reactions at very low loadings of palladium (ppm levels). The chemistry described here, combining fundamental organometallic, catalysis, and pure organic methodology, remains rich in opportunities considering that only a handful of palladium(II) architectures have been studied. Hence, en route to an "ideal catalyst", [(NHC)Pd(II)] compounds exhibit remarkable stability and allow for fine-tuning of the NHC and of surrounding ligands in order to control the activation and the catalytic activity. Finally, unlike [Pd(PPh(3))(4)], [(NHC)Pd(II)] compounds have so far been examined only in palladium-mediated reactions (most often cross-coupling such as the Suzuki-Miyaura and Heck reactions), leaving a treasure trove of exciting discoveries to come.

[(NHC)AuI]-catalyzed rearrangement of allylic acetates.

[(NHC)AuCl] complexes (NHC = N-heterocyclic carbene), in conjunction with a silver salt, were found to efficiently catalyze the rearrangement of allylic acetates under both conventional and microwave-assisted heating. The optimization of several reaction parameters (solvent, silver salt, and ligand) as well as a study of the reaction scope are reported. The steric hindrance of the ligand bound to gold was found crucial for the outcome of the reaction as only extremely bulky ligands permitted the isomerization.

[(NHC)AuI]-catalyzed formation of conjugated enones and enals: an experimental and computational study.

The [(NHC)AuI]-catalyzed (NHC=N-heterocyclic carbene) formation of alpha,beta-unsaturated carbonyl compounds (enones and enals) from propargylic acetates is described. The reactions occur at 60 degrees C in 8 h in the presence of an equimolar mixture of [(NHC)AuCl] and AgSbF6 and produce conjugated enones and enals in high yields. Optimization studies revealed that the reaction is sensitive to the solvent, the NHC, and, to a lesser extent, to the silver salt employed, leading to the use of [(ItBu)AuCl]/AgSbF6 in THF as an efficient catalytic system. This transformation proved to have a broad scope, enabling the stereoselective formation of (E)-enones and -enals with great structural diversity. The effect of substitution at the propargylic and acetylenic positions has been investigated, as well as the effect of aryl substitution on the formation of cinnamyl ketones. The presence or absence of water in the reaction mixture was found to be crucial. From the same phenylpropargyl acetates, anhydrous conditions led to the formation of indene compounds via a tandem [3,3] sigmatropic rearrangement/intramolecular hydroarylation process, whereas simply adding water to the reaction mixture produced enone derivatives cleanly. Several mechanistic hypotheses, including the hydrolysis of an allenol ester intermediate and SN2' addition of water, were examined to gain an insight into this transformation. Mechanistic investigations and computational studies support [(NHC)AuOH], produced in situ from [(NHC)AuSbF6] and H2O, instead of cationic [(NHC)AuSbF6] as the catalytically active species. Based on DFT calculations performed at the B3LYP level of theory, a full catalytic cycle featuring an unprecedented transfer of the OH moiety bound to the gold center to the C[triple chemical bond]C bond leading to the formation of a gold-allenolate is proposed.

N-heterocyclic carbenes as organocatalysts.

Organocatalyzed reactions represent an attractive alternative to metal-catalyzed processes notably because of their lower cost and benign environmental impact in comparison to organometallic catalysis. In this context, N-heterocyclic carbenes (NHCs) have been studied for their ability to promote primarily the benzoin condensation. Lately, dramatic progress in understanding their intrinsic properties and in their synthesis have made them available to organic chemists. This has resulted in a tremendous increase of their scope and in a true explosion of the number of papers reporting NHC-catalyzed reactions. Here, we highlight the ever-increasing number of reactions that can be promoted by N-heterocyclic carbenes.

Au(I)-catalyzed cycloisomerization of 1,5-enynes bearing a propargylic acetate: formation of unexpected bicyclo[3.1.0]hexene.

The use of N-heterocyclic carbene (NHC) as a ligand in the gold(I)-catalyzed cycloisomerization of enyne results in the assembly of a new carbocyclic product.

(IPr)Pd(acac)Cl: an easily synthesized, efficient, and versatile precatalyst for C-N and C-C bond formation.

A very straightforward synthesis of (IPr)Pd(acac)Cl from two commercially available starting materials, Pd(acac)2 and IPr.HCl [acac = acetylacetonate; IPr = N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene], has been developed. The resulting complex, (IPr)Pd(acac)Cl (1), has proven to be a highly active PdII precatalyst in the Buchwald-Hartwig and the alpha-ketone arylation reactions. A wide range of substrates has been screened, including unactivated, sterically hindered, and heterocyclic aryl chlorides.

Rapid room temperature Buchwald-Hartwig and Suzuki-Miyaura couplings of heteroaromatic compounds employing low catalyst loadings.

The use of second-generation [(NHC)Pd(R-allyl)Cl] complexes for Suzuki-Miyaura and Buchwald-Hartwig cross-coupling reactions involving heteroaromatic halides at room temperature is reported. The first examples of room temperature Suzuki-Miyaura cross-coupling of deactivated aryl chlorides with alkenyl boronic acids are also disclosed. Terminal substitution at the allyl moiety of the palladium complex facilitates its activation at room temperature leading to very active catalytic species enabling the present catalytic transformations to be performed rapidly using very mild reaction conditions. Catalyst loadings can be as low as 10 ppm for the Buchwald-Hartwig aryl amination and 50 ppm for the Suzuki-Miyaura reaction.