Gold-catalyzed intramolecular cyclization of alkynones with pyridine anhydrobases

4-Alkylpyridines functionalized with alkynyl amide substituents can be converted to pyridyl-substituted lactams via Au-catalyzed cyclization at the pyridine benzylic carbon. These transformations proceed through alkylidene dihydropyridine (anhydrobase) intermediates and demonstrate the ability to utilize these species in metal-catalyzed C–C bond forming reactions.     

Sequential alkylation/gold-catalyzed annulation reactions of anilines with propargylic bromide derivatives

Preliminary results of sequential alkylation/gold-catalyzed annulation reactions of anilines with propargylic bromide derivatives to provide quinoline scaffolds are described. The efficiency of NaAuCl₄·2H₂O in the sequential procedure was investigated and compared with different transition metal salts and Au(I) complexes. Selectivity of the reaction of aniline derivatives with propargylic bromides has also been investigated.     

Gold-catalyzed intramolecular hydroamination of α-amino allenamides as a route to enantiopure 2-vinylimidazolidinones

An efficient gold-catalyzed procedure for the preparation of 2-vinylimidazolidinones has been developed. The starting materials for the synthesis of these compounds are α-amino allenamides which undergo heterocyclization by means of nucleophilic attack of the amino group on the inside double bond of the 1,2-diene moiety. This is the first example of a gold-catalyzed cyclization on allene substrates bearing an amido group which, however, resulted inactive.     

Transition metal catalyzed hydroarylation of olefins using unactivated substrates: Recent developments and challenges

The addition of aromatic C-H bonds across olefin CC bonds (olefin hydroarylation) is an important synthetic methodology for the preparation of alkylated arenes. Traditional methods utilizing Friedel-Crafts catalysts result in a significant waste stream and substantial polyalkyated products. In order to achieve high overall yield of monoalkylated compounds, Friedel-Crafts catalysis must be combined with a second transalkylation catalytic step. Reactions that incorporate substituted olefins are selective for branched products. In addition, the regioselective synthesis of disubstituted alkyl arenes is difficult to achieve. Recent development of transition metal based catalysts provides non-Friedel-Crafts pathways for the production of alkyl arenes. Systems based on Ru(II), Ir(III), and Pt(II) have been developed, and mechanistic studies have begun to provide insight into the details of these catalysts. Herein, we review recently published results in the area of transition metal catalyzed olefin hydroarylation with a comparison of known catalysts and discussion of challenges yet to be overcome.     

First-principle studies of intermolecular and intramolecular catalysis of protonated cocaine

We have performed a series of first-principles electronic structure calculations to examine the reaction pathways and the corresponding free energy barriers for the ester hydrolysis of protonated cocaine in its chair and boat conformations. The calculated free energy barriers for the benzoyl ester hydrolysis of protonated chair cocaine are close to the corresponding barriers calculated for the benzoyl ester hydrolysis of neutral cocaine. However, the free energy barrier calculated for the methyl ester hydrolysis of protonated cocaine in its chair conformation is significantly lower than for the methyl ester hydrolysis of neutral cocaine and for the dominant pathway of the benzoyl ester hydrolysis of protonated cocaine. The significant decrease of the free energy barrier, approximately 4 kcal/mol, is attributed to the intramolecular acid catalysis of the methyl ester hydrolysis of protonated cocaine, because the transition state structure is stabilized by the strong hydrogen bond between the carbonyl oxygen of the methyl ester moiety and the protonated tropane N. The relative magnitudes of the free energy barriers calculated for different pathways of the ester hydrolysis of protonated chair cocaine are consistent with the experimental kinetic data for cocaine hydrolysis under physiologic conditions. Similar intramolecular acid catalysis also occurs for the benzoyl ester hydrolysis of (protonated) boat cocaine in the physiologic condition, although the contribution of the intramolecular hydrogen bonding to transition state stabilization is negligible. Nonetheless, the predictability of the intramolecular hydrogen bonding could be useful in generating antibody-based catalysts that recruit cocaine to the boat conformation and an analog that elicited antibodies to approximate the protonated tropane N and the benzoyl O more closely than the natural boat conformer might increase the contribution from hydrogen bonding. Such a stable analog of the transition state for intramolecular catalysis of cocaine benzoyl-ester hydrolysis was synthesized and used to successfully elicit a number of anticocaine catalytic antibodies.     

Iron-catalyzed synthesis of phenanthrenes via intramolecular hydroarylation of arene-alkynes

An Fe(OTf)₃-catalyzed intramolecular hydroarylation of arene-alkynes with high functional group tolerance has been reported, affording a series of phenanthrene derivatives efficiently. A low catalytic amount of Fe(OTf)₃ is applied in this reaction. This transformation provides a convenient and practical method for the preparation of phenanthrenes.     

Theoretical studies of intramolecular electron transfer reactions: Distance and free energy dependences

Electron tunneling through a square potential energy barrier is used to calculate the distance-dependent factors of electron transfer (ET) processes in metal-monolayer-metal junctions, donors and acceptors dispersed in rigid organic glasses, intramolecular ET in rigid donorbridge—acceptor species in solution and redox centers attached to electrodes through adsorbed monolayers. This tunneling model of distancedependent non-adiabatic factors is incorporated in the intersecting state model (ISM). The result is a simple semiclassical theory which is used to calculate the rates of non-adiabatic ET reactions. When the electron is originally located in a π* molecular orbital of the donor and the reaction free energy is no lower than approximately −50 kJ mol⁻¹, no adjustable parameters are necessary to calculate the intramolecular ET rates from a donor, through a rigid bridge, to an acceptor. Such calculated rates are within an order of magnitude of the experimental values. The model can also account for the ET rates of more exothermic reactions provided that the value of an empirical parameter, which is constant for structurally related reactants and solvents of similar polarity, is estimated. The physical meaning of this parameter is related to the dynamics of the reactions. The profiles of the distance and free energy dependences of photoinduced ET rates are closely reproduced. The occurrence of distance-dependent non-adiabatic factors in intermolecular σ*-d ETs is rationalized.     

Gold-catalyzed intramolecular hydroamination of allenes: a case of chirality transfer

The hydroamination of allenes proceeded smoothly in the presence of gold catalysts to give the corresponding 2-vinyl pyrrolidines and piperidines in high yields. The reaction is very efficient and can be carried out with only 1-5 mol % catalyst at room temperature and under extremely mild conditions. As an example of chirality transfer, it is shown that aminoallene 1a (96% ee), synthesized from (S)-(−)-1-octyn-3-ol, was converted into the corresponding pyrrolidine 2a (94% ee) in 99% yield.     

Gold-catalyzed rearrangement of substituted allyl aryl ethers

Triphenylphosphinegold(I) complexes catalyze the Claisen-type rearrangement of aryl allyl ethers to the corresponding branched and linear products. The product distribution depends on the olefin geometry of the allylic ether. Stereochemical transfer experiments support an ionic mechanism.     

Gold-catalyzed cyclization of tert-butyl allenoate: general synthesis of 2,4-functionalized butenolides

AuCl₃ efficiently catalyzes cyclization of tert-butyl allenoates into γ-butenolides. Advantage of directly using allenic ester precursor instead of corresponding acid is demonstrated in the synthesis of a variety of 2,4-disubstituted butenolides. A low catalyst loading and mild reaction condition makes this process an attractive alternative over conventional methods using strong Lewis acids.     

Catalytic activity of gold nanoclusters in intramolecular hydroamination of alkenes and alkynes with toluenesulfonamide under aerobic and basic conditions

Gold nanoclusters stabilized by a hydrophilic polymer, poly(N-vinyl-2-pyrrolidone) (Au:PVP), catalyzed the intramolecular hydroamination of toluenesulfonamides to unactivated alkenes/alkynes in EtOH under aerobic and basic conditions. The reaction proceeds via anti-addition of toluenesulfonamide to the alkenes assisted by π-activation of the gold clusters.     

Scope and mechanistic studies of electrophilic alkoxyetherification

A one-pot electrophilic alkoxyetherification using an olefin, a cyclic ether, a carboxylic acid, and N-bromosuccinimide has been developed. The oxygen nucleophiles, the olefinic substrates, and the cyclic ether partners can be varied to produce a wide range of alkoxyether derivatives.     

Gold-catalyzed intermolecular hydroalkoxylation of allenes; difference in mechanism between hydroalkoxylation and hydroamination

A wide range of alcohols 2 react with various allenes 1 in the presence of ClAuPPh₃/AgOTf catalyst at ambient temperature without solvent to produce allylic ethers 3. Contrary to the hydroamination, which proceeds through high chiral-face selectivity for chiral allenes to give the corresponding chiral allylic amines, transfer of chirality is not observed in the hydroalkoxylation, suggesting that the mechanism of the gold-catalyzed hydroalkoxylation is different from that of hydroamination.     

Gold-catalyzed cascade C–C and C–N bond formation: synthesis of polysubstituted indolequinones and pyrroles

The combination of Ph₃PAuCl and AgOTf was proven to be an efficient catalyst for the cascade C–C and C–N bond formation reactions from enamines and bromoquinones or nitroolefins. This protocol affords a straightforward method for the synthesis of polysubstituted indolequinones and pyrroles in good yields.     

Selectivity studies in the reaction between iodobenzene and phenylacetylene: Sonogashira coupling vs hydroarylation

The selectivity of the coupling reaction between iodobenzene and phenylacetylene was evaluated. Several palladium catalysts, ligands and reaction conditions were tested, showing that supported catalysts, room temperature or ionic liquids (NHC precursors) favor Sonogashira coupling, while the non‐supported ones, higher temperature and PPh₃ as ligand, favor hydroarylation. Neither excess of iodobenzene nor phenylboronic acids are required; and it is possible to avoid the use of PPh₃, although this lowers selectivity. Copyright © 2008 John Wiley & Sons, Ltd.     

Palladium complexes of phosphinamine ligands in the intramolecular asymmetric Heck reaction

The synthesis of two novel cyclisation substrates for the asymmetric intramolecular Heck reaction is reported. Their cyclisation, in addition to a known substrate for cis-decalin formation, were tested with palladium complexes of BINAP and heterobidentate oxazoline-containing ligands. In general BINAP provides a more active catalyst system for the range of substrates tested although excellent enantioselectivities of up to 85% were obtained with the P,N ligands studied. A trend was noted whereby the t-leucine-derived oxazoline ligands were more reactive and enantioselective than the valine-derived analogues. Similarly, the diphenylphosphinoferrocenyloxazoline ligands were more reactive and selective than the corresponding diphenylphosphinophenyloxazoline ligands.     

金催化炔基苯并二𫫇英环化合成8-羟基异香豆素的理论研究

Density functional theory（DFT） calculations were carried out on the gold-catalyzed cyclization of alkynyl benzodioxin to 8-hydroxy-isocoumarin reaction to show the molecular mechanism of the reaction. The conclusions obtained from this work are different from those in the previous experimental study. The results show that water molecule acts as both the reactant and the proton shuttle, and promotes the reaction with gold complexes under mild conditions. The nucleophilic addition site of water on the substrate is the C（sp³） atom on the side of the substrate far away from the oxabenzene ring, resulting in C（sp³）—O bond breaking in the substrate. The formation of new C—O bond and the cleavage of C—O bond in the substrate follow a step-by-step mechanism. The oxygen in the side-product acetone comes from the contribution of water in the reaction system. The regioselectivity of the reaction originates from the polarization of alkynyl π-electrons induced by substituents.