Gold-catalyzed Hydroamination Research Articles

Gold-Catalyzed Access to Pyrrolo- and (Aryl)Indolo-Fused Phenazines.

Novel fused phenazines were synthesized through a combination of gold-catalyzed hydroamination and cascade cyclization reactions towards azaacenes. In total, 30 new compounds were synthesized and investigated with respect to their structural and optoelectronic properties. In solution, these targets exhibit strong green to red emission, with quantum yields of up to 60%. The emission wavelength can be finely adjusted by the choice of solvent due to their solvatochromic behavior, as demonstrated with a representative example.

Increasing the Donor Strength of Alkenylphosphines by Twisting the C=C Double Bond.

Electron-rich phosphines play a crucial role in transition metal-based homogeneous catalysis. While alkyl groups have traditionally been employed to increase the phosphine donor strength, recent studies have shown that zwitterionic functional groups such as phosphorus ylides can result in a further enhancement. Herein we report the concept of twisting a C=C double bond to introduce a zwitterionic substituent by the synthesis and application of N-heterocyclic olefin phosphines with a sulfonyl substituent (sNHOP). This sulfonyl group enables the twisting of the olefin moiety due to steric and electronic stabilization of the carbanionic center. The resulting zwitterionic structure leads to a significant increase of the donor strength of the sNHOP ligands compared to conventional NHOP systems with a planar N-heterocyclic olefin moiety. The potential of this new ligand platform for catalysis is demonstrated by its application in the gold-catalyzed hydroamination and cyclo-isomerization of alkynes. Here, the ligands outperform the original NHOP ligands suggesting favorable properties for future catalysis applications.

One-Pot Synthesis of Polycyclic Sultams Enabled by Gold-Catalyzed Hydroamination of o-Alkynylbenzenesulfonamides and Subsequent Iodine(III)-Mediated Counteranion-Assisted Intramolecular Annulation.

Herein we present a facile and efficient one-pot synthetic protocol for the construction of polycyclic sultams. This protocol involves gold-catalyzed intramolecular hydroamination of o-alkynylbenzenesulfonamides followed by HTIB-mediated counteranion-assisted intramolecular annulation. The transformation tolerates a wide range of functional groups, resulting in the formation of highly functionalized and valuable polycyclic sultam skeletons in moderate to excellent yields. These polycyclic sultams are widely used as key building blocks in organic science.

Gold Catalyzed 7-endo-dig Hydroaminations Yielding 1,4-Diazepineones.

Strategies to access the 1,4-diazepindiones heterocyclic core of the TAN-1057 family of natural products revealed a successful gold-catalyzed hydroamination of yneamide tethered amines. The precursor amino-yneamides are derived from easily accessible 1,2-diamines and alkynoic acids and are efficiently cyclized to the corresponding diazepineones.

Kinetics and Mechanisms of the Gold-Catalyzed Hydroamination of Axially Chiral 1-Aryl-1,2-butadienes with Aniline

The mechanisms of the hydroamination of enantiomerically enriched, axially chiral (R)-1-aryl-1,2-butadienes (R)-(4-C6H4R)C(H)=C=C(H)Me [R = Ph (1a), OMe (1b)] with aniline catalyzed by (IPr)AuOTf have been investigated employing a combination of kinetic and stereochemical analyses and in situ spectroscopy of catalytically active mixtures. These experiments were consistent with mechanisms involving essentially irreversible displacement of aniline from [(IPr)Au(NH2Ph)]+ by allene (R)-1 to form the enantiomerically enriched gold−π-allene intermediate {(R)-(IPr)Au[η2-(R)-ArC(H)=C=C(H)Me]}+ [(R)-I], followed by unimolecular stereomutation to form the racemic gold−π-allene intermediate rac-I. Intermediate rac-I, in turn, undergoes either allene displacement to form racemic allene rac-1 or C–N bond formation/protodeauration to form racemic (E)-N-(4-aryl-3-buten-2-yl)aniline (rac-2), favoring the former pathway by a factor of ∼2.4. As such, approximately 30% of the racemic product rac-2 is formed directly from (R)-1 without the intermediacy of rac-1.

Straightforward Synthesis of α-Chloromethylketimines Catalyzed by Gold(I). A Clean Way to Building Blocks.

α-Chloromethylketimines have been obtained through a gold-catalyzed hydroamination of aromatic and aliphatic 1-chloroalkynes with aromatic amines by using equimolar amounts of both reagents. This procedure has allowed the preparation and spectroscopic characterization of α-chloromethylketimines for the first time with a high degree of purity, complete conversion, and atom economy. The synthetic usefulness of the methodology has been demonstrated with the preparation of β-chloroamines and indoles.

Kinetics and Mechanism of the Gold-Catalyzed Hydroamination of 1,1-Dimethylallene with N-Methylaniline.

The mechanism of the intermolecular hydroamination of 3-methylbuta-1,2-diene (1) with N-methylaniline (2) catalyzed by (IPr)AuOTf has been studied by employing a combination of kinetic analysis, deuterium labelling studies, and in situ spectral analysis of catalytically active mixtures. The results of these and additional experiments are consistent with a mechanism for hydroamination involving reversible, endergonic displacement of N-methylaniline from [(IPr)Au(NHMePh)]+ (4) by allene to form the cationic gold π-C1,C2-allene complex [(IPr)Au(η2 -H2 C=C=CMe2 )]+ (I), which is in rapid, endergonic equilibrium with the regioisomeric π-C2,C3-allene complex [(IPr)Au(η2 -Me2 C=C=CH2 )]+ (I'). Rapid and reversible outer-sphere addition of 2 to the terminal allene carbon atom of I' to form gold vinyl complex (IPr)Au[C(=CH2 )CMe2 NMePh] (II) is superimposed on the slower addition of 2 to the terminal allene carbon atom of I to form gold vinyl complex (IPr)Au[C(=CMe2 )CH2 NMePh] (III). Selective protodeauration of III releases N-methyl-N-(3-methylbut-2-en-1-yl)aniline (3 a) with regeneration of 4. At high conversion, gold vinyl complex II is competitively trapped by an (IPr)Au+ fragment to form the cationic bis(gold) vinyl complex {[(IPr)Au]2 [C(=CH2 )CMe2 NMePh]}+ (6).

De Novo Approach to Izidines via A Gold-Catalyzed Hydroamination–N-acyliminium Ion Cyclization of Acyclic Ynamides

De Novo Approach to Izidines via A Gold-Catalyzed Hydroamination–N-acyliminium Ion Cyclization of Acyclic Ynamides

DFT study on the “Silver effect” in gold-catalyzed hydroamination of terminal alkynyl sulfamides

The mechanism and “silver effect” in regiodivergent gold-catalyzed hydroamination of terminal alkynyl sulfamides have been explored by the density functional theory (DFT) in the model systems composed of [AuCl(Ph3P)]/AgOTf (series A), AuCl(Ph3P)]/K2CO3 (series B) and [AuCl(Ph3P)]/Ag2CO3 (series C). Our results clearly showed that the regioselectivity of the terminal alkynyl sulfamides is mainly controlled by true involvement of Ag in the catalysis when using different silver salts as a component of gold-based catalytic system, rather than the steric effect. In the [AuCl(Ph3P)]/AgOTf and [AuCl(Ph3P)]/Ag2CO3 catalytic systems, the formation of π-activation or σ-gold-π-silver intermediates turns more favorable the 6-endo-dig cyclization in comparison with the 5-exo-dig pathway. On the other hand, the 5-exo-dig cyclization involving a three-membered Au-C-Au ring activated alkyne intermediate is likely the major pathway for the [AuCl(Ph3P)]/K2CO3 catalytic system. Furthermore, the regioselectivity and its origin as well as the rationalization of “silver effect” are also examined and discussed in detail.

Stereo- and regioselective gold(i)-catalyzed hydroamination of 2-(arylethynyl)pyridines with anilines.

The gold-catalyzed hydroamination of 2-(arylethynyl)pyridines with anilines affords stereoselectively Z-enamine products with excellent regioselectivity. The reaction proceeds with moderate to excellent yields and accommodates a diverse range of functional groups on alkynes (ether, bromo, trifluoromethyl, acetyl, and carbomethoxy) and anilines (ether, bromo, chloro, and carbethoxy). The stereochemistry of the obtained enamines is complementary to that reported in previous studies. A plausible explanation for the observed selectivity was attained by means of NMR experiments.

Dialkyl(1,3-diarylimidazolin-2-ylidenamino)phosphines: Strongly Electron-Donating, Buchwald-Type Phosphines

The synthesis and properties of a series of strongly electron-donating, sterically demanding dialkyl(1,3-diarylimidazolin-2-ylidenamino)phosphines (IAPs) are reported. Determination of the TEP values shows that the bulky IAPs are better donor ligands than classical N-heterocyclic carbenes. The steric profiles of the IAPs in neutral and cationic gold(I) complexes were analyzed by X-ray diffraction studies and computational methods, revealing similar structural features to the Buchwald-type phosphines. The new phosphines were tested in the gold-catalyzed hydroamination of phenylacetylene with anilines.

ChemInform Abstract: Chiral Ditopic Cyclophosphazane (CycloP) Ligands: Synthesis, Coordination Chemistry, and Application in Asymmetric Catalysis.

A series of dichlorocyclophosphazanes [{ClP(μ-NR)}2 ] containing chiral and achiral R groups was obtained from simple commercially available amines and PCl3 . Their condensation reactions with axially chiral biaryl diols yielded ansa-bridged chiral cyclophosphazane (CycloP) ligands. This highly modular methodology allows extensive elaboration of the ligand set, in which the chirality can be introduced at the diol bridge and/or the amido R group. This provides the possibility to observe match and mismatch effects in catalysis. A series of twenty CycloP ligands was synthesized and characterized by multinuclear NMR spectroscopy, HRMS, elemental analysis, and in selected cases, single-crystal X-ray diffraction. These studies show that all of the ditopic CycloP ligands are C2 symmetric, rendering their metal coordination sites symmetry equivalent. Two well-established enantioselective reactions were explored by using late-transition metal CycloP complexes as catalysts; the gold-catalyzed hydroamination of γ-allenyl sulfonamides and the asymmetric nickel-catalyzed three-component coupling of a diene and an aldehyde. The steric demands of the CycloP ligands have a subtle influence on the reactivity and selectivity observed in both reactions. Good enantiomeric ratios (e.r.) as high as 89:11 in the gold-catalyzed reaction and 92:8 in the nickel-catalyzed bis-homoallylation reaction were observed.

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

A new approach to the total synthesis of (−)-epimyrtine has been developed from D-alanine. The key step to access the enantiopure pyridone intermediate was achieved by a gold-mediated cyclization. Finally, various transformations afforded the natural product in a few steps and good overall yield.

Combination of gold catalysis and Selectfluor for the synthesis of fluorinated nitrogen heterocycles

We herein report the synthesis of 3-fluoro-2-methylene-pyrrolidine (3a) and -piperidine (3b) from 1,5- and 1,6-aminoalkynes, respectively, using a combination of a gold-catalyzed hydroamination reaction followed by electrophilic trapping of an intermediate cyclic enamine by Selectfluor. Careful attention was paid to the elucidation of the mechanism and Selectfluor was suggested to play the double role of promoting the oxidation of gold(I) to a gold(III) active species and also the electrophilic fluorination of the enamine intermediates.

Gold-Catalyzed Hydroamination of Internal Alkynes

This paper describes an efficient method to synthesize functionalized enamines. Utilizing gold catalysis, densely functionalized enamines can be obtained directly from an internal alkyne and an amine. The products are also produced in high regio- and stereoselectivities from symmetrical and unsymmetrical alkynes in most cases.

Stereo- and Regioselective Gold-Catalyzed Hydroamination of Internal Alkynes with Dialkylamines

We report the use of a P,N-ligand to support a gold complex as a state-of-the-art precatalyst for the stereoselective hydroamination of internal aryl alkynes with dialkylamines to afford E-enamine products. Substrates featuring a diverse range of functional groups on both the amine (ether, sulfide, N-Boc amine, fluoro, nitrile, nitro, alcohol, N-heterocycles, amide, ester, and carboxylic acid) and alkyne (ether, N-heterocycles, N-phthalimide amines, and silyl ethers) are accommodated with synthetically useful regioselectivity.

Gold‐Catalyzed Hydroamination of C—C Multiple Bonds

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