Synthesis of Alkenylgold(I) Complexes Relevant to Catalytic Carboxylative Cyclization of Unsaturated Amines and Alcohols.

The carboxylation of unsaturated amine and alcohol compounds, including 4-benzylamino-1-phenyl-1-butyne (homopropargylamine), 2-butyne-1-ol (propargylic alcohol), and 2,3-butadiene-1-ol (allenylmethyl alcohol), using the hydroxidogold(I) complex, AuOH(IPr) [IPr = 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene], produces corresponding alkenylgold(I) complexes with a cyclic urethane or carbonate framework in high yields. The reaction takes place in aprotic THF at room temperature under the atmospheric pressure of CO2 in the absence of base additives. The products were characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The functionalized alkenyl complexes prepared from the alkynes can be protonated by treatment with an equimolar amount of acetic acid to afford five- or six-membered carboxylation products, whereas the related alkenyl complex derived from allenylmethyl alcohol decomposed to recover the starting allene via ring-opening decarboxylation.

Asymmetric Reductive Amination of α-Keto Acids Using Ir-Based Hydrogen Transfer Catalysts: An Access to Unprotected Unnatural α-Amino Acids.

A direct asymmetric reductive amination of α-keto acids catalyzed by Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand is described. The combined use of optically active 2-phenyglycinol as an aminating agent is effective for the chemo- and stereoselective transfer hydrogenation using formic acid. The subsequent elimination of the hydroxyethyl moiety by orthoperiodic acid can afford various unprotected α-amino acids in satisfactory isolated yields (20 examples) with excellent optical purities (up to >99% ee).

Asymmetric Transfer Hydrogenative Amination of Benzylic Ketones Catalyzed by Cp*Ir(III) Complexes Bearing a Chiral N-(2-Picolyl)sulfonamidato Ligand.

A convenient asymmetric reductive amination of benzylic ketones (α-arylated ketones) catalyzed by newly designed Cp*Ir complexes bearing a chiral N-(2-picolyl)sulfonamidato ligand was developed. Using readily available ß-amino alcohols as chiral aminating agents, a range of benzo-fused and acyclic ketones were successfully reduced with formic acid in methanol at 40 °C to afford amines with favorable chemo- and diastereoselectivities. The amino alcohol-derived chiral auxiliary was easily removed by mild periodic oxidants, leading to optically active primary ß-arylamines without erosion of the optical purity (up to 97% ee). The excellent catalytic performance was retained even upon lowering the amount of catalyst to a substrate/catalyst (S/C) ratio of 20,000, and the amination could be performed on a large scale exceeding 100 g. The precise hydride transfer to iminium species generated from the ketonic substrate and the chiral amine counterpart was suggested by the mechanistic studies on stoichiometric reactions of isolable hydridoiridium complexes and model intermediates such as N,O-acetal, enamine, and iminium compounds.

Oxy-tethered Cp*Ir(III) complex as a competent catalyst for selective dehydrogenation from formic acid.

A bifunctional tethered iridium catalyst containing a 1,2-diphenylethylenediamine framework was synthesised for the first time. The ethereal tether chain was easily constructed via the intramolecular oxydefluorination of a perfluorophenylsulfonyl substituent by using a modified 1,2,3,4,5-pentamethylcyclopentadienyl ligand with a hydroxyalkyl chain. The conformationally constrained structure could hamper deactivation pathways in the catalytic hydrogen generation from formic acid, leading to advanced durability and complete conversion.

New Bifunctional Bis(azairidacycle) with Axial Chirality via Double Cyclometalation of 2,2'-Bis(aminomethyl)-1,1'-binaphthyl.

As a candidate for bifunctional asymmetric catalysts containing a half-sandwich C-N chelating Ir(III) framework (azairidacycle), a dinuclear Ir complex with an axially chiral linkage is newly designed. An expedient synthesis of chiral 2,2'-bis(aminomethyl)-1,1'-binaphthyl (1) from 1,1-bi-2-naphthol (BINOL) was accomplished by a three-step process involving nickel-catalyzed cyanation and subsequent reduction with Raney-Ni and KBH4. The reaction of (S)-1 with an equimolar amount of [IrCl2Cp*]2 (Cp* = η5-C5(CH3)5) in the presence of sodium acetate in acetonitrile at 80 °C gave a diastereomeric mixture of new dinuclear dichloridodiiridium complexes (5) through the double C-H bond cleavage, as confirmed by 1H NMR spectroscopy. A loss of the central chirality on the Ir centers of 5 was demonstrated by treatment with KOC(CH3)3 to generate the corresponding 16e amidoiridium complex 6. The following hydrogen transfer from 2-propanol to 6 provided diastereomers of hydrido(amine)iridium retaining the bis(azairidacycle) architecture. The dinuclear chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation of acetophenone with a substrate to a catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, leading to (S)-1-phenylethanol with up to an enantiomeric excess (ee) of 67%.

Convincing Catalytic Performance of Oxo-Tethered Ruthenium Complexes for Asymmetric Transfer Hydrogenation of Cyclic α-Halogenated Ketones through Dynamic Kinetic Resolution.

A highly efficient dynamic kinetic resolution of cyclic halohydrins was achieved by the asymmetric transfer hydrogenation of racemic α-haloketones. Bifunctional oxo-tethered Ru(II) catalysts could promote the reduction without deterioration of halogens. By structural tuning of the catalyst, chiral alcohols having halogen, ester, carboxamide, and sulfone functions were obtained variably with excellent diastereo- and enantioselectivities (up to >99:1 d.r. and >99.9 ee), which provided a concise synthetic approach to a dopamine D3 receptor ligand, (+)-PHNO.

Transfer hydrogenation of carbon dioxide via bicarbonate promoted by bifunctional C-N chelating Cp*Ir complexes.

Metal-ligand cooperative Cp*Ir(iii) complexes derived from primary benzylic amines effectively promote transfer hydrogenation of atmospheric CO2 using 2-propanol at 80 °C. Isotope-labelling experiments strengthen that active Ir species can preferentially reduce bicarbonate congeners formed from CO2. The powerful transfer hydrogenation catalyst exhibits remarkable activity for the conversion of bicarbonates into formate salts with a turnover number up to 3200, even without H2 and CO2.

Formal Deoxygenative Hydrogenation of Lactams Using PNHP-Pincer Ruthenium Complexes under Nonacidic Conditions.

A formal deoxygenative hydrogenation of amides to amines with RuCl2(NHC)(PNHP) (NHC = 1,3-dimethylimizadol-2-ylidene, PNHP = bis(2-diphenylphosphinoethyl)amine) is described. Various secondary amides, especially NH-lactams, are reduced with H2 (3.0-5.0 MPa) to amines at a temperature range of 120-150 °C with 1.0-2.0 mol % of PNHP-Ru catalysts in the presence of Cs2CO3. This process consists of (1) deaminative hydrogenation of secondary amides to generate primary amines and alcohols, (2) dehydrogenative coupling of the transient amines with alcohols to generate imines, and (3) hydrogenation of imines to give the formally deoxygenated secondary amine products.

Multiple Absolute Stereocontrol in Cascade Lactone Formation via Dynamic Kinetic Resolution Driven by the Asymmetric Transfer Hydrogenation of Keto Acids with Oxo-Tethered Ruthenium Catalysts.

A straightforward asymmetric construction of chiral fused γ- and δ-lactones containing multiple contiguous stereocenters was successfully developed by either (1) the dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) reaction using oxo-tethered Ru(II) complexes followed by syn-selective lactonization or (2) the tandem DKR-ATH/lactonization in combination with asymmetric hydrogenation catalyzed by Ru-chiral diphosphine complexes. The expedient protocol is applicable to the enantioselective synthesis of natural wine lactone and a biologically active benzo-fused lactone with an unprecedented level of diastereo- and enantioselectivity.

Reductive Amination of Ketonic Compounds Catalyzed by Cp*Ir(III) Complexes Bearing a Picolinamidato Ligand.

Cp*Ir complexes bearing a 2-picolinamide moiety serve as effective catalysts for the direct reductive amination of ketonic compounds to give primary amines under transfer hydrogenation conditions using ammonium formate as both the nitrogen and hydrogen source. The clean and operationally simple transformation proceeds with a substrate to catalyst molar ratio (S/C) of up to 20,000 at relatively low temperature and exhibits excellent chemoselectivity toward primary amines.

Cleavage of N-H Bond of Ammonia via Metal-Ligand Cooperation Enables Rational Design of a Conceptually New Noyori-Ikariya Catalyst.

The asymmetric transfer hydrogenation (ATH) of ketones/imines with Noyori-Ikariya catalyst represents an important reaction in both academia and fine chemical industry. The method allows for the preparation of chiral secondary alcohols/amines with very good to excellent optical purities. Remarkably, the same chiral Noyori-Ikariya complex is also a precatalyst for a wide range of other chemo- and stereoselective reductive and oxidative transformations. Among them are enantioselective sulfonamidation of acrylates (intramolecular aza-Michael reaction) and carboxylation of indoles with CO2. Development of these catalytic reactions has been inspired by the realized cleavage of the N-H bond of sulfonamides and indoles by the 16e- amido derivative of the 18e- precatalyst via metal-ligand cooperation (MLC). This paper summarizes our efforts to investigate N-H bond cleavage of gaseous ammonia in solution via MLC and reports the serendipitous discovery of a new class of chiral tridentate κ3[ N, N', N″] Ru and Ir metallacycles, derivatives of the famous M-FsDPEN catalysts (M = Ru, Ir). The protonation of these metallacycles by strong acids containing weakly coordinating (chiral) anions generates ionic complexes, which were identified as conceptually novel Noyori-Ikariya precatalysts. For example, the ATH of aromatic ketones with some of these complexes proceeds with up to 99% ee.

Accessible Bifunctional Oxy-Tethered Ruthenium(II) Catalysts for Asymmetric Transfer Hydrogenation.

A concise synthesis of new oxy-tethered ruthenium complexes effective for the asymmetric transfer hydrogenation of aromatic ketones is described. The oxy-tether was constructed via a defluorinative etherification arising from an intramolecular nucleophilic substitution of a perfluorinated phenylsulfonyl substituent. The obtained tethered complexes exhibited desirable catalytic activity and selectivity, especially in the asymmetric transfer hydrogenation of functionalized aromatic ketones. The robustness and rigidity of the tether contribute to their superior catalytic performance relative to the nontethered prototype complex.

N-Monomethylation of Aromatic Amines with Methanol via PNHP-Pincer Ru Catalysts.

The use of methanol for the selective methylation of aromatic amines with RuHCl(CO)(PNHP) (PNHP = bis(2-diphenylphosphinoethyl)amine) is reported. Various aromatic amines were transformed into their corresponding monomethylated secondary amines in high yields at 150 °C with a very low catalyst loading (0.02-0.1 mol %) in the presence of KO tBu (20-60 mol %). The catalyst precursor, RuHCl(CO)(PNHP), was converted to [RuH(CO)2(PNHP)]+ under the catalytic conditions and also serves as a highly effective catalyst. The robustness of this catalyst contributes to its outstanding catalytic activity, even under reaction conditions, in which CO is liberated from methanol.

Protic NNN and NCN Pincer-Type Ruthenium Complexes Featuring (Trifluoromethyl)pyrazole Arms: Synthesis and Application to Catalytic Hydrogen Evolution from Formic Acid.

NNN and NCN pincer-type ruthenium(II) complexes featuring two protic pyrazol-3-yl arms with a trifluoromethyl (CF3 ) group at the 5-position were synthesized and structurally characterized to evaluate the impact of the substitution on the properties and catalysis. The increased Brønsted acidity by the highly electron-withdrawing CF3 pendants was demonstrated by protonation-deprotonation experiments. By contrast, the IR spectra of the carbonyl derivatives as well as the cyclic voltammogram indicated that the electron density of the ruthenium atom is negligibly influenced by the CF3 group. Catalysis of these complexes in the decomposition of formic acid to dihydrogen and carbon dioxide was also examined. The NNN pincer-type complex 1 a with the CF3 group exhibited a higher catalytic activity than the tBu-substituted analogue 1 b. In addition, the bis(CF3 -pyrazolato) ammine derivative 4 catalyzed the reaction even in the absence of base additives.

Comparative Study of Bifunctional Mononuclear and Dinuclear Amidoiridium Complexes with Chiral C-N Chelating Ligands for the Asymmetric Transfer Hydrogenation of Ketones.

A series of new bifunctional C-N chelating Ir complexes possessing a metal/NH group was synthesized by cyclometalation of optically active primary benzylic amines such as O-silylated (S)-2-amino-2-phenylethanols (1 a and 1 a'), (R)-5-amino-6,7,8,9-tetrahydro-5H-benzocycloheptene (1 b), and (R)-1-phenyl-2,2-dimethylpropylamine (1 c). Although treatment of KOtBu with the amine complexes originating from 1 a and 1 a' afforded amido-bridged dinuclear complexes (3 a and 3 a'), more sterically hindered complexes were solely transformed into the coordinatively unsaturated mononuclear amido complexes (3 b and 3 c), which can serve as real catalyst species in the asymmetric transfer hydrogenation. The structural difference in the C-N chelate framework markedly affected the catalytic performance. Among them, amido complex 3 c showed a pronounced ability to catalyze the transfer hydrogenation of acetophenone in 2-propanol, even at a low temperature of -30 °C. A hydridoiridium complex (4 c) was also identified in the reaction of 3 c in 2-propanol, which provides mechanistic insights into the enantiodiscriminating step in the hydrogen transfer to prochiral ketones.

Efficient Access to Chiral Benzhydrols via Asymmetric Transfer Hydrogenation of Unsymmetrical Benzophenones with Bifunctional Oxo-Tethered Ruthenium Catalysts.

A concise asymmetric transfer hydrogenation of diaryl ketones, promoted by bifunctional Ru complexes with an etherial linkage between 1,2-diphenylethylenediamine (DPEN) and η(6)-arene ligands, was successfully developed. Because of the effective discrimination of substituents at the ortho position on the aryl group, unsymmetrical benzophenones were smoothly reduced in a 5:2 mixture of formic acid and triethylamine with an unprecedented level of excellent enantioselectivity. For the non-ortho-substituted benzophenones, the oxo-tethered catalyst electronically discerned biased substrates, resulting in attractive performance yielding chiral diarylmethanols with >99% ee.

Atmospheric Hydrogenation of Esters Catalyzed by PNP-Ruthenium Complexes with an N-Heterocyclic Carbene Ligand.

New pincer ruthenium complexes bearing a monodentate N-heterocyclic carbene ligand were synthesized and demonstrated as powerful hydrogenation catalysts. With an atmospheric pressure of hydrogen gas, aromatic, heteroaromatic, and aliphatic esters as well as lactones were converted into the corresponding alcohols at 50 °C. This reaction protocol offers reliable access to alcohols using an easy operational setup.

Enhanced Hydrogen Generation from Formic Acid by Half-Sandwich Iridium(III) Complexes with Metal/NH Bifunctionality: A Pronounced Switch from Transfer Hydrogenation.

By switching the catalytic function from transfer hydrogenation based on the metal/NH bifunctionality, facile dehydrogenation of formic acid was achieved by amido- and hydrido(amine)-Ir complexes derived from N-triflyl-1,2-diphenylethylenediamine (TfDPEN) at ambient temperature even in the absence of base additives. Further acceleration was observed by the addition of water, leading to a maximum turnover frequency above 6000 h(-1). A proton-relay mechanism guided by the protic amine ligand and water is postulated for effective protonation of metal hydrides.

Highly selective carboxylative cyclization of allenylmethylamines with carbon dioxide using N-heterocyclic carbene-silver(I) catalysts.

Silver(I) carboxylate complexes promote the carboxylative cyclization of allenylmethylamines to afford 5-alkenyl-1,3-oxazolidin-2-ones in 2-propanol. The use of an N-heterocyclic carbene ligand (IPr) under pressurized CO2 is effective in suppressing the intramolecular hydroamination that leads to 2,5-dihydropyrroles. The mechanism involving a nucleophilic attack of the carbamate of the allene moiety and a subsequent protonation was realized on the basis of experimental and theoretical results involving a model intermediate, the alkenylgold(I) complex, which was synthesized from Au(OH)(IPr) and 1-methylamino-2,3-butadiene.

Efficient dynamic kinetic resolution of racemic secondary alcohols by a chemoenzymatic system using bifunctional iridium complexes with C-N chelate amido ligands.

The combined catalyst system of bifunctional amidoiridium complexes derived from benzylic amines with CALB was found to provide a range of chiral acetates from racemic secondary alcohols in excellent yields with nearly perfect enantioselectivities via dynamic kinetic resolution.