Acceptorless Dehydrogenative Oxidation of Secondary Alcohols Catalysed by Cp*IrIII–NHC Complexes

A series of new Ir^III complexes with carbene ligands that contain a range of benzyl wingtip groups have been prepared and fully characterised by NMR spectroscopy, HRMS, elemental analysis and X‐ray diffraction. All the complexes were active in the acceptorless dehydrogenation of alcohol substrates in 2,2,2‐trifluoroethanol to give the corresponding carbonyl compounds. The most active complex bore an electron‐rich carbene ligand; this complex was used to catalyse the highly efficient and chemoselective dehydrogenation of a wide range of secondary alcohols to their respective ketones, with turnover numbers up to 1660. Mechanistic studies suggested that the turnover of the dehydrogenation reaction is limited by the H₂‐formation step.     

Iridium‐Catalyzed Dehydrogenative Decarbonylation of Primary Alcohols with the Liberation of Syngas

A new iridium ‐ catalyzed reaction in which molecular hydrogen and carbon monoxide are cleaved from primary alcohols in the absence of any stoichiometric additives has been developed. The dehydrogenative decarbonylation was achieved with a catalyst generated in situ from [Ir(coe)₂Cl]₂ (coe=cyclooctene) and racemic 2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl (rac‐BINAP) in a mesitylene solution saturated with water. A catalytic amount of lithium chloride was also added to improve the catalyst turnover. The reaction has been applied to a variety of primary alcohols and gives rise to products in good to excellent yields. Ethers, esters, imides, and aryl halides are stable under the reaction conditions, whereas olefins are partially saturated. The reaction is believed to proceed by two consecutive organometallic transformations that are catalyzed by the same iridium(I)–BINAP species. First, dehydrogenation of the primary alcohol to the corresponding aldehyde takes place, which is then followed by decarbonylation to the product with one less carbon atom.     

Selective Iridium‐Catalyzed Alkylation of (Hetero)Aromatic Amines and Diamines with Alcohols under Mild Reaction Conditions

Selective amine alkylation : A P,N‐ligand‐stabilized iridium complex has been used as an efficient catalyst for the alkylation of (hetero)aromatic amines with alcohols at mild reaction temperatures and catalyst loadings as low as 0.1 mol % Ir (see scheme). The excellent selectivity of the catalyst for monoalkylation of the amine function has also been exploited for the N,N′‐dialkylation of diamines in both symmetric and nonsymmetric fashions.

     

Iridium‐Catalyzed Intermolecular Dehydrogenative Silylation of Polycyclic Aromatic Compounds without Directing Groups

This study describes the iridium‐catalyzed intermolecular dehydrogenative silylation of C(sp²)?H bonds of polycyclic aromatic compounds without directing groups. The reaction produced various arylsilanes through both Si?H and C?H bond activation, with hydrogen as the sole byproduct. Reactivity was affected by the electronic nature of the aromatic compounds, and silylation of electron‐deficient and polycyclic aromatic compounds proceeded efficiently. Site‐selectivity was controlled predominantly by steric factors. Therefore, the current functionalization proceeded with opposite chemo‐ and site‐selectivity compared to that observed for general electrophilic functionalization of aromatic compounds.     

Cobalt‐Catalyzed Alkylation of Aromatic Amines by Alcohols

The implementation of inexpensive, Earth‐abundant metals in typical noble‐metal‐mediated chemistry is a major goal in homogeneous catalysis. A sustainable or green reaction that has received a lot of attention in recent years and is preferentially catalyzed by Ir or Ru complexes is the alkylation of amines by alcohols. It is based on the borrowing hydrogen or hydrogen autotransfer concept. Herein, we report on the Co‐catalyzed alkylation of aromatic amines by alcohols. The reaction proceeds under mild conditions, and selectively generates monoalkylated amines. The observed selectivity allows the synthesis of unsymmetrically substituted diamines. A novel Co complex stabilized by a PN₅P ligand catalyzes the reactions most efficiently.     

Manganese‐Catalyzed Dehydrogenative Alkylation or α‐Olefination of Alkyl‐Substituted N‐Heteroarenes with Alcohols

Catalysis with earth‐abundant transition metals is an option to help save our rare noble‐metal resources and is especially interesting when novel reactivity or selectivity patterns are observed. We report here on a novel reaction, namely the dehydrogenative alkylation or α‐olefination of alkyl‐substituted N‐heteroarenes with alcohols. Manganese complexes developed in our laboratory catalyze the reaction with high efficiency whereas iron and cobalt complexes stabilized by the same ligands are essentially inactive. Hydrogen is liberated during the reaction, and bromine and iodine functional groups as well as olefins are tolerated. A variety of alkyl‐substituted N‐heteroarenes can be functionalized, and benzylic and aliphatic alcohols undergo the reaction.     

Iridium‐Catalyzed Coupling Reaction of Primary Alcohols with 2‐Alkynes Leading to Hydroacylation Products

A novel iridium‐catalyzed intermolecular coupling reaction of primary alcohols or aldehydes with 2‐alkynes was successfully achieved with high regioselectivity to give hydroacylation products such as α,β‐unsaturated ketones in good yields. The mechanistic investigation of the reaction strongly indicated that the coupling proceeds through the initial formation of homoallylic alcohols followed by dehydrogenation to β,γ‐unsatutated ketones and then isomerisation, which leads to the hydroacylation products.     

Iridium‐Catalyzed Asymmetric Hydrogenation of 3,3‐Disubstituted Allylic Alcohols in Ethereal Solvents

Ir‐phosphinomethyl‐oxazoline complexes have been identified as efficient, highly enantioselective catalysts for the asymmetric hydrogenation of 3,3‐disubstituted allylic alcohols and related homoallylic alcohols. In contrast to other N,P ligand complexes, which require weakly coordinating solvents, such as dichloromethane, these catalysts perform well in more ecofriendly THF or 2‐MeTHF. Their synthetic potential was demonstrated with the formal total synthesis of four bisabolane sesquiterpenes.     

Efficient and Inexpensive Synthesis of Benzimidazoles and Quinoxalines

o-Phenylenediamines were reacted with carbonyl compounds, β-ketoesters, and 1,2-diketones in presence of ammonium salts to give benzimidazoles and quinoxalines in very good yields. Ammonium salts are commercial and environmentally benign catalysts.     

Amide Synthesis from Alcohols and Amines Catalyzed by Ruthenium N‐Heterocyclic Carbene Complexes

The direct synthesis of amides from alcohols and amines is described with the simultaneous liberation of dihydrogen. The reaction does not require any stoichiometric additives or hydrogen acceptors and is catalyzed by ruthenium N‐heterocyclic carbene complexes. Three different catalyst systems are presented that all employ 1,3‐diisopropylimidazol‐2‐ylidene (IiPr) as the carbene ligand. In addition, potassium tert‐butoxide and a tricycloalkylphosphine are required for the amidation to proceed. In the first system, the active catalyst is generated in situ from [RuCl₂(cod)] (cod=1,5‐cyclooctadiene), 1,3‐diisopropylimidazolium chloride, tricyclopentylphosphonium tetrafluoroborate, and base. The second system uses the complex [RuCl₂(IiPr)(p‐cymene)] together with tricyclohexylphosphine and base, whereas the third system employs the Hoveyda–Grubbs 1st‐generation metathesis catalyst together with 1,3‐diisopropylimidazolium chloride and base. A range of different primary alcohols and amines have been coupled in the presence of the three catalyst systems to afford the corresponding amides in moderate to excellent yields. The best results are obtained with sterically unhindered alcohols and amines. The three catalyst systems do not show any significant differences in reactivity, which indicates that the same catalytically active species is operating. The reaction is believed to proceed by initial dehydrogenation of the primary alcohol to the aldehyde that stays coordinated to ruthenium and is not released into the reaction mixture. Addition of the amine forms the hemiaminal that undergoes dehydrogenation to the amide. A catalytic cycle is proposed with the {(IiPr)Ru^II} species as the catalytically active components.     

New Iridium Catalysts for the Selective Alkylation of Amines by Alcohols under Mild Conditions and for the Synthesis of Quinolines by Acceptor‐less Dehydrogenative Condensation

A novel family of iridium catalysts stabilised by P,N‐ligands have been introduced. The ligands are based on imidazo[1,5‐b]pyridazin‐7‐amines and can be synthesised with a broad variety of substitution patterns. The catalysts were synthesised quantitatively from the protonated ligands and a commercially available iridium precursor. The catalysts mediate the alkylation of amines by alcohols under mild conditions (70 °C). In addition, the synthesis of quinolines from secondary or primary alcohols and amino alcohols is reported. This sustainable synthesis proceeds through the liberation of two equivalents of water and two equivalents of dihydrogen. The investigations indicate that catalysts suitable for hydrogen autotransfer or borrowing hydrogen chemistry might also be suitable for acceptor‐less dehydrogenative condensation reactions.     

Chromium‐Catalyzed Alkylation of Amines by Alcohols

The alkylation of amines by alcohols is a broadly applicable, sustainable, and selective method for the synthesis of alkyl amines, which are important bulk and fine chemicals, pharmaceuticals, and agrochemicals. We show that Cr complexes can catalyze this C?N bond formation reaction. We synthesized and isolated 35 examples of alkylated amines, including 13 previously undisclosed products, and the use of amino alcohols as alkylating agents was demonstrated. The catalyst tolerates numerous functional groups, including hydrogenation‐sensitive examples. Compared to many other alcohol‐based amine alkylation methods, where a stoichiometric amount of base is required, our Cr‐based catalyst system gives yields higher than 90 % for various alkyl amines with a catalytic amount of base. Our study indicates that Cr complexes can catalyze borrowing hydrogen or hydrogen autotransfer reactions and could thus be an alternative to Fe, Co, and Mn, or noble metals in (de)hydrogenation catalysis.     

Iridium‐Catalyzed Asymmetric Isomerization of Primary Allylic Alcohols

Nothing to sm(Ir)k at : Under appropriate reaction conditions, iridium hydride catalysts promote the isomerization of primary allylic alcohols. The best catalysts, like (R)‐ 1 (P green, O red, N blue, Ir yellow), deliver the desired chiral aldehydes with excellent enantioselectivity and good yields. Mechanistic hypotheses have been developed on the basis of preliminary investigations.

     

Iridium‐Catalyzed Enantioselective Allylic Alkylation with Functionalized Organozinc Bromides

Iridium‐catalyzed enantioselective allylic alkylation of branched racemic carbonates with functionalized alkylzinc bromide reagents is described. Enabled by a chiral Ir/(P,olefin) complex, the method described allows allylic substitution with various primary and secondary alkyl nucleophiles with excellent regio‐ and enantioselectivities. The developed reaction was showcased in a concise, asymmetric synthesis of (?)‐preclamol.     

Enantioselective Synthesis of Vicinal All‐Carbon Quaternary Centers via Iridium‐Catalyzed Allylic Alkylation

The development of the first enantioselective transition‐metal‐catalyzed allylic alkylation providing access to acyclic products bearing vicinal all‐carbon quaternary centers is disclosed. The iridium‐catalyzed allylic alkylation reaction proceeds with excellent yields and selectivities for a range of malononitrile‐derived nucleophiles and trisubstituted allylic electrophiles. The utility of these sterically congested products is explored through a series of diverse chemo‐ and diastereoselective product transformations to afford a number of highly valuable, densely functionalized building blocks, including those containing vicinal all‐carbon quaternary stereocenters.     

Synthesis,Structure, and Catalytic Activity of Cyclometalated Iridium Complexes with a Bidentate POC Ligand

Synthesis, characterization and catalytic activity of cyclometalated iridium complexes with a bidentate POC ligand is presented. Metalation of POC-H (di-tert-butyl(phenoxy)phosphane) with [Ir(COD)Cl]₂ proceeded rapidly at room temperature and afforded mixture of (POC)(POC-H)IrHCl ( 1 a ) and (POC)(COD)IrHCl ( 1 b ), from which complexes (POC)(L)IrHCl where L=PPh₃ ( 1 c ), bipyridine ( 1 d ) and [2,2′-bipyridine]-6,6′-diol ( 1 e ) were prepared through ligand exchange. The compounds were tested in acceptorless dehydrogenation of 1-phenylethanol and transfer dehydrogenation of ethanol in a context of comparison with pincer counterparts (POCOP)IrHCl and (PCN)IrHCl. An attempt to prepare a dihydride complex from 1 e led to dimeric complex [(POC)(bipy-diol−)IrH]₂ ( 3 ) that could explain the low activity of 1 e . DFT studies provided insight into POC-H vs POCOP-H metalation mechanism.     

Iridium‐Catalyzed Stereoselective Allylic Alkylation Reactions with Crotyl Chloride

The development of the first enantio‐, diastereo‐, and regioselective iridium‐catalyzed allylic alkylation reaction of prochiral enolates to form an all‐carbon quaternary stereogenic center with an aliphatic‐substituted allylic electrophile is disclosed. The reaction proceeds with good to excellent selectivity with a range of substituted tetralone‐derived nucleophiles furnishing products bearing a newly formed vicinal tertiary and all‐carbon quaternary stereodyad. The utility of this protocol is further demonstrated via a number of synthetically diverse product transformations.