Gold Catalysis: One‐Pot Alkylideneoxazoline Synthesis/Alder‐Ene Reaction

Based on the gold‐catalyzed synthesis of methyleneoxazolines, a one‐pot combination with an Alder‐ene reaction was developed. For azodicarboxylates, good to very good yields (51–99 %) of the oxazolemethylhydrazinedicarboxylates were achieved with 3 mol % of the Gagosz catalyst, [Ph₃PAuNTf₃]. In a less‐selective reaction, 4‐phenyl‐3H‐1,2,4‐triazol‐3,5(4 H)‐dione gave lower yields (41–49 %) of the corresponding oxazolemethylphenyltriazolidinediones. Overall, five new bonds were formed. Tetracyanoethylene afforded a cyclobutane derivative through a [2+2] cycloaddition reaction at ?40 °C, but only 45 % of the spiro compound was obtained. The less‐readily available KITPHOS ligands on gold gave even higher yields at lower catalyst loadings (2 mol %), but longer reaction times were required.     

Acidic Co‐Catalysts in Cationic Gold Catalysis

A systematic study on the effects of Lewis or Brønsted acid co‐catalysts in gold‐catalyzed reactions was undertaken using representative reactions (O‐, N‐, and C‐nucleophilic additions to alkynes). Through these reactions, it was demonstrated that an acidic co‐catalyst can increase the catalyst turnover significantly, enabling practical reaction rates at competitive catalyst loadings (<1 mol %). Further investigation is currently underway to improve the understanding of the subtle principles underlying these experimental observations.     

Highly Efficient and Stereoselective Thioallylation of Alkynes: Possible Gold Redox Catalysis with No Need for a Strong Oxidant

Stereoselective thioallylation of alkynes under possible gold redox catalysis was accomplished with high efficiency (as low as 0.1 % catalyst loading, up to 99 % yield) and broad substrate scope (various alkynes, inter‐ and intramolecular fashion). The gold(I) catalyst acts as both a π‐acid for alkyne activation and a redox catalyst for Au^I/III coupling, whereas the sulfonium cation generated in situ functions as a mild oxidant. This novel methodology provides an exciting system for gold redox catalysis without the need for a strong oxidant.     

Meeting the Challenge of Intermolecular Gold(I)‐Catalyzed Cycloadditions of Alkynes and Allenes

The development of gold(I)‐catalyzed intermolecular carbo‐ and hetero‐cycloadditions of alkynes and allenes has been more challenging than their intramolecular counterparts. Here we review, with a mechanistic perspective, the most fundamental intermolecular cycloadditions of alkynes and allenes with alkenes.     

The AZARYPHOS Family of Ligands for Ambifunctional Catalysis: Syntheses and Use in Ruthenium‐Catalyzed anti‐Markovnikov Hydration of Terminal Alkynes

The family of AZARYPHOS (aza–aryl–phosphane) phosphane ligands, containing a phosphine unit and sterically shielded nitrogen lone pairs in the ligand periphery, is introduced as a tool for developing ambifunctional catalysis by the metal center and nitrogen lone pairs in the ligand sphere. General synthetic strategies have been developed to synthesize over 25 examples of structurally diverse (6‐aryl‐2‐pyridyl)phosphanes (ARPYPHOS), (6‐alkyl‐2‐pyridyl)phosphanes (ALPYPHOS), 4,6‐disubsituted 1,3‐diazin‐2‐ylphosphanes or 1,3,5‐triazin‐2‐ylphosphanes, quinazolinylphosphanes, quinolinylphosphanes, and others. The scalable syntheses proceed in a few steps. The incorporation of AZARYPHOS ligands ( L ) into complexes [RuCp( L )₂(MeCN)][PF₆] (Cp=cyclopentadienyl) gives catalysts for the anti‐Markovnikov hydration of terminal alkynes of the highest known activities. Electronic and steric ligand effects modulate the reaction kinetics over a range of two orders of magnitude. These results highlight the importance of using structurally diverse ligand families in the process of developing cooperative ambifunctional catalysis by a metal and its ligand.     

Gold(I)‐Catalyzed Diastereoselective Hydroacylation of Terminal Alkynes with Glyoxals

The reaction of an α‐ketoaldehyde and a terminal alkyne in the presence of piperidine and a catalytic amount of AuCl delivers 1,2‐dicarbonyl‐3‐enes, products of the formal hydroacylation of the triple bond. The scope of the method is broad; different aryl substituents on the dicarbonyl unit and on the alkyne are well tolerated. The products can be transformed selectively into vinylquinoxalines. Mechanistic studies, including isotope‐labeling experiments, indicate that after an initial A³‐type conversion to propargylic amines, a subsequent base‐mediated alkyne‐to‐allene isomerization and a hydrolysis of the enamine substructure during the workup deliver the formal hydroacylation products.     

Regioselective Hydration of Alkynes by Iron(III) Lewis/Brønsted Catalysis

The triflimide iron(III) salt [Fe(NTf₂)₃] promotes the direct hydration of terminal and internal alkynes with very good Markovnikov regioselectivities and high yields. The enhanced carbophilic Lewis acidity of the Fe^III cation mediated by the weakly‐coordinating triflimide anion is crucial for the catalytic activity. The iron(III) metal salt can be recycled in the form of the OPPh₃/[Fe(NTf₂)₃] system with similar activity and selectivity. However, spectroscopic and kinetic studies show that [Fe(NTf₂)₃] hydrolyzes under the reaction conditions and that catalytically less active Brønsted species are formed, which points to a Lewis/Brønsted co‐catalysis. This triflimide‐based catalytic system is regioselective for the hydration of internal aryl‐alkynes and opens the door to a new synthetic route to alkyl ketophenones. As a proof of concept, the synthesis of two antipsychotics Haloperidol and Melperone, with general butyrophenone‐like structure, is shown.     

Room‐Temperature Hydrohydrazination of Terminal Alkynes Catalyzed by Saturated Abnormal N‐Heterocyclic Carbene–Gold(I) Complexes

A number of saturated abnormal N‐heterocyclic carbene (NHC) complexes of gold, in combination with KBAr^F₄ as activator, were successfully applied in the chemoselective addition of hydrazine to alkynes. The reaction proceeds even at room temperature, which was not possible to date with gold catalysts. The reaction can be applied to a number of substituted arylalkynes. With alkylalkynes the yields are low. The saturated abnormal NHC ligands are resistant to isomerization to the saturated normal NHC coordination mode under basic reaction conditions. Under acidic conditions, a simple protonation at the nitrogen atom not neighboring the carbene center was observed and unambiguously characterized by an X‐ray crystal‐structure analysis. Computational studies confirm that such an isomerization would be highly exothermic, the observed kinetic stability probably results from the need to shift two protons in such a process.     

Broad‐Spectrum Catalysts for the Ambient Temperature Anti‐Markovnikov Hydration of Alkynes

Anti‐Markovnikov alkyne hydration provides a valuable route to aldehydes. Half‐sandwich ruthenium complexes ligated by 5,5′‐bis(trifluoromethyl)‐2,2′‐bipyridine are remarkably active for this transformation. In the presence of 2 mol % metal, a wide range of functionalized aliphatic and aromatic alkynes are hydrated in high yield at ambient temperature.     

Catalytic Selective Dihydrosilylation of Internal Alkynes Enabled by Rare‐Earth Ate Complex

Hydrosilylation of alkynes generally yield vinylsilanes, which are inert to the further hydrosilylation because of the steric effects. Reported here is the first successful dihydrosilylation of aryl‐ and silyl‐substituted internal alkynes enabled by a rare‐earth ate complex to yield geminal bis‐ and tris(silanes), respectively. The lanthanum bis(amido) ate complex supported by an ene‐diamido ligand proved to be the ideal catalyst for this unprecedented transformation, while the same series of yttrium and samarium alkyl and samarium bis(amido) ate complexes exhibited poor activity and selectivity, indicating significant effects of the ionic size and ate structure of the rare‐earth catalysts.