Hiroshi Naka

Hydration of Terminal Alkynes Catalyzed by Water-Soluble Cobalt Porphyrin Complexes

Water-soluble cobalt(III) porphyrin complexes were found to promote the hydration of terminal alkynes to give methyl ketones. The alkyne hydration proceeded in good to excellent yield with 0.1 to 2 mol % cobalt catalyst 1 and was compatible with the presence of acid/base- or redox-sensitive functional groups such as alkyl silyl ethers; allyl ethers; trityl ethers; benzyl ethers; carboxylic esters; boronic esters; carboxamides; nitriles; and nitro, iodo, and acetal groups. Some of the alkyne substrates tested here are otherwise difficult to hydrate. The alkyne hydration can be performed on a gram scale, and the catalyst can be recovered by aqueous workup.

Mixed alkylamido aluminate as a kinetically controlled base.

The mechanisms by which directed ortho metalation (DoM) and postmetalation processes occur when aromatic compounds are treated with mixed alkylamido aluminate i-Bu3Al(TMP)Li (TMP-aluminate 1; TMP = 2,2,6,6-tetramethylpiperidide) have been investigated by computation and X-ray diffraction. Sequential reaction of ArC(=O)N(i-Pr)2 (Ar = phenyl, 1-naphthyl) with t-BuLi and i-Bu3Al in tetrahydrofuran affords [2-(i-Bu3Al)C(m)H(n)C(=O)N(i-Pr)2]Li x 3 THF (m = 6, n = 4, 7; m = 10, n = 6, 8). These data advance the structural evidence for ortho-aluminated functionalized aromatics and represent model intermediates in DoM chemistry. Both 7 and 8 are found to resist reaction with HTMP, suggesting that ortho-aluminated aromatics are incapable of exhibiting stepwise deprotonative reactivity of the type recently shown to pertain to the related field of ortho zincation chemistry. Density functional theory calculations corroborate this view and reveal the existence of substantial kinetic barriers both to one-step alkyl exchange and to amido-alkyl exchange after an initial amido deprotonation reaction by aluminate bases. Rationalization of this dichotomy comes from an evaluation of the inherent Lewis acidities of the Al and Zn centers. As a representative synthetic application of this high kinetic reactivity of the TMP-aluminate, the highly regioselective deprotonative functionalization of unsymmetrical ketones both under mild conditions and at elevated temperatures is also presented.

N-Methylation of Amines with Methanol at Room Temperature

N-Methylation of amines with methanol proceeds at room temperature in the presence of a silver-loaded titanium dioxide (Ag/TiO2) photocatalyst under UV-vis light irradiation. This method allows facile synthesis/isolation of N-methylamines bearing various functional groups including N-benzyl, N-allyl, N-Boc, hydroxyl, ether, acetal, carboxamide, formamide, and olefin groups.

Organozinc reagents in DMSO solvent: remarkable promotion of SN2' reaction for allene synthesis.

The S N2 reaction of propragyl mesylates with organozinc reagents was dramatically improved in DMSO solvent, and the stereoselective conversion of chiral substrates was successfully achieved using LiCl-free diorganozinc without the loss of optical purity.

Chiral eta(6)-Arene/N-Tosylethylenediamine-Ruthenium(II) Complexes: Solution Behavior and Catalytic Activity for Asymmetric Hydrogenation

Aromatic ketones are enantioseletively hydrogenated in alcohols containing [RuX{(S,S)-Tsdpen}(eta(6)-p-cymene)] (Tsdpen=TsNCH(C(6)H(5))CH(C(6)H(5))NH(2); X=TfO, Cl) as precatalysts. The corresponding Ru hydride (X=H) acts as a reducing species. The solution structures and complete spectral assignment of these complexes have been determined using 2D NMR ((1)H-(1)H DQF-COSY, (1)H-(13)C HMQC, (1)H-(15)N HSQC, and (1)H-(19)F HOESY). Depending on the nature of the solvents and conditions, the precatalysts exist as a covalently bound complex, tight ion pair of [Ru(+)(Tsdpen)(cymene)] and X(-), solvent-separated ion pair, or discrete free ions. Solvent effects on the NH(2) chemical shifts of the Ru complexes and the hydrodynamic radius and volume of the Ru(+) and TfO(-) ions elucidate the process of precatalyst activation for hydrogenation. Most notably, the Ru triflate possessing a high ionizability, substantiated by cyclic voltammetry, exists in alcoholic solvents largely as a solvent-separated ion pair and/or free ions. Accordingly, its diffusion-derived data in CD(3)OD reflect the independent motion of [Ru(+)(Tsdpen)(cymene)] and TfO(-). In CDCl(3), the complex largely retains the covalent structure showing similar diffusion data for the cation and anion. The Ru triflate and chloride show similar but distinct solution behavior in various solvents. Conductivity measurements and catalytic behavior demonstrate that both complexes ionize in CH(3)OH to generate a common [Ru(+)(Tsdpen)(cymene)] and X(-), although the extent is significantly greater for X=TfO(-). The activation of [RuX(Tsdpen)(cymene)] during catalytic hydrogenation in alcoholic solvent occurs by simple ionization to generate [Ru(+)(Tsdpen)(cymene)]. The catalytic activity is thus significantly influenced by the reaction conditions.

Chiral Bisphosphazides as Dual Basic Enantioselective Catalysts

Chiral bisphosphazides complexed with lithium salts efficiently catalyze the direct enantioselective 1,4-addition of dialkyl malonates to acyclic enones. Spectroscopic studies on the stoichiometry of the bisphosphazide and lithium salt have indicated the formation of a 1:1 species as the active enantioselective catalyst. It is suggested that the catalyst generates a complex of the protonated phosphazide and the chiral nucleophile as the key intermediate. The phosphazide moiety appears to be a promising dual basic functionality for stereo- and chemoselective catalytic transformations.

One‐Pot Nitrile Aldolization/Hydration Operation Giving β‐Hydroxy Carboxamides

Carboxamide functionalities (CONH2) are versatile synthetic intermediates or building blocks, and have been widely used in the Hofmann rearrangement, N-arylation, N-allylation, and N-alkylation reactions. In addition, CONH2 is a useful protected form of carboxylic acid [5] and a potent pharmacophore in many drug candidates. Therefore, a catalytic chemical transformation incorporating the CR2CONH2 moiety (R= H or alkyl) into a molecular framework through a carboxamide enolate, thus effecting a carbon carbon bond-forming reaction would be of considerable practical importance. However, such a reaction has thus far remained elusive, primarily due to the considerably low acidity of the a-proton of carboxamide in comparison to CONH2 (pKa =~25 in dimethyl sulfoxide). The pKa value of carboxamides in dimethyl sulfoxide is approximately 35, the highest value out of those reported for aldehydes and ketones (pKa =~27 in dimethyl sulfoxide), or for esters (pKa =~31 in dimethyl sulfoxide). Herein, we report an alternative pathway to break out of this problem (Scheme 1). The formal aldol products of carboxamides were obtainable by the RhOR-catalyzed aldoltype reaction (R=H, Me) of nitriles (pKa =~31 in dimethyl sulfoxide), followed by in situ hydration of the nitrile functionality. This consecutive process was accommodated in a one-pot operation that minimized the amount and different varieties of salt wastes. First, the rhodium(I) catalyst was prepared by treatment of [Rh ACHTUNGTRENNUNG(OMe) ACHTUNGTRENNUNG(cod)]2 (cod=cycloocta-l,5-diene) with Cy3P (1:2; Cy=cyclohexyl) in anhydrous tetrahydrofuran at 25 8C for 15 minutes under argon. After removal of tetrahydrofuran and residual cycloocta-l,5-diene in vacuo, argon-filled tert-butanol was added to yield a solution of rhodium catalyst. Nitrile aldolization was carried out by using PhCHO (1 a) and acetonitrile (2 a) with the rhodium(I) catalyst at 25 8C (Rh: 1.0 10 2 m). Subsequent removal of any volatile components including excess acetonitrile gave a bright red/ orange slurry containing b-hydroxy nitrile 4 aa. Addition of argon-filled isopropanol, followed by treatment with Na2CO3 and H2O at 25 8C, gave b-hydroxy carboxamide 3 aa in 96 % yield. Likely dehydration products, such as a,bunsaturated carboxamide and nitrile, were not detected. Addition of a catalytic amount of Na2CO3 was critical for this one-pot operation. In the absence of Na2CO3, little hy[a] Dr. A. Goto, Dr. R. Noyori, Dr. S. Saito Department of Chemistry Graduate School of Science Nagoya University Chikusa, Nagoya 464-8602 (Japan) Fax: (+81) 52-789-5945 E-mail : saito.susumu@f.mbox.nagoya-u.ac.jp [b] Dr. H. Naka, Dr. R. Noyori Research Center for Materials Science Nagoya University Chikusa, Nagoya 464-8602 (Japan) [c] Dr. R. Noyori, Dr. S. Saito Institute for Advanced Research Nagoya University Chikusa, Nagoya 464-8601 (Japan) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201000921. Scheme 1. General scheme of the nitrile aldolization/hydration sequence.

Hydration of nitriles to amides by a chitin-supported ruthenium catalyst

Chitin-supported ruthenium (Ru/chitin) promotes the hydration of nitriles to carboxamides under aqueous conditions. The nitrile hydration can be performed on a gram-scale and is compatible with the presence of various functional groups including olefins, aldehydes, carboxylic esters and nitro and benzyloxycarbonyl groups. The Ru/chitin catalyst is easily prepared from commercially available chitin, ruthenium(III) chloride and sodium borohydride. Analysis of Ru/chitin by high-resolution transmission electron microscopy indicates the presence of ruthenium nanoparticles on the chitin support.

Activation of organozinc reagents with t-Bu-P4 base for transition metal-free catalytic SN2′ reaction

The t-Bu-P4 base was found to be an excellent catalyst for activating organozinc reagents and was used to promote the S(N)2 reaction of alpha,beta-unsaturated esters bearing a gamma-chloride using various organozinc reagents: these reactions proceeded in high yields with excellent chemo-and regioselectivity.

Why p-Cymene? Conformational Effect in Asymmetric Hydrogenation of Aromatic Ketones with a η6-Arene/Ruthenium(II) Catalyst

The global reaction route mapping (GRRM) methods conveniently define transition states in asymmetric hydrogenation and transfer hydrogenation of aromatic ketones via the [RuH{(S,S)-TsNCH(C6 H5 )CH(C6 H5 )NH2 }(η(6) -p-cymene)] intermediate. Multiple electrostatic CH/π interactions are the common motif in the preferred diastereometric structures.