Economical and Readily Accessible Preparation of o,o-Disubstituted Arylboronates through Palladium-Catalyzed Borylation of Haloarenes.

Miyaura borylation, that is, palladium-catalyzed cross-coupling between bromoarenes and diboron, offers a versatile method for preparing arylboronates; however, a costly and inaccessible catalyst has been required for synthesizing highly congested arylboronates with the method. Here the Pd(OAc)2-tri(4-methoxyphenyl)phosphine catalyst was found to work as an efficient catalyst for the sterically demanding borylation. A broad range of o,o-disubstituted bromoarenes were converted into the corresponding arylboronates in high yields by using the palladium catalyst with Cs2CO3 in EtOAc at 80 °C.

Ruthenium-Catalyzed Chemo- and Enantioselective Hydrogenation of Isoquinoline Carbocycles.

A chemoselective hydrogenation of isoquinoline carbocycles was achieved by using the catalyst prepared from Ru(methallyl)2(cod) and trans-chelate chiral ligand PhTRAP. The unique chemoselectivity achieved in this hydrogenation could be ascribed to the trans-chelation of the chiral ligand. The procedure for preparing the catalyst strongly affects the reproducibility of the carbocycle hydrogenation. Various 5-, 6-, 7-, and 8-substituted isoquinolines were selectively hydrogenated at their carbocycles to afford 5,6,7,8-tetrahydroisoquinolines as major products in high yields with moderate or good enantioselectivities. Some mechanistic studies suggested that the stereogenic center was created during the initial addition of H2 to the aromatic ring in the hydrogenation of 5-substituted isoquinolines. In other words, the stereochemical control was accompanied by the dearomatization.

Asymmetric Hydrogenation of Azaindoles: Chemo- and Enantioselective Reduction of Fused Aromatic Ring Systems Consisting of Two Heteroarenes.

High enantioselectivity was achieved for the hydrogenation of azaindoles by using the chiral catalyst, which was prepared from [Ru(η(3) -methallyl)2 (cod)] and a trans-chelating bis(phosphine) ligand (PhTRAP). The dearomative reaction exclusively occurred on the five-membered ring, thus giving the corresponding azaindolines with up to 97:3 enantiomer ratio.

Asymmetric Hydrogenation of Isoxazolium Triflates with a Chiral Iridium Catalyst.

The iridium catalyst [IrCl(cod)]2 -phosphine-I2 (cod=1,5-cyclooctadiene) selectively reduced isoxazolium triflates to isoxazolines or isoxazolidines in the presence of H2 . The iridium-catalyzed hydrogenation proceeded in high-to-good enantioselectivity when an optically active phosphine-oxazoline ligand was used. The 3-substituted 5-arylisoxazolium salts were transformed into 4-isoxazolines with up to 95:5 enantiomeric ratio (e.r.). Chiral cis-isoxazolidines were obtained in up to 89:11 e.r., with no formation of their trans isomers, when the substrates had a primary alkyl substituent at the 5-position. The mechanistic studies indicate that the hydridoiridium(III) species prefers to deliver its hydride to the C5 atom of the isoxazole ring. The hydride attack leads to the formation of the chiral isoxazolidine via a 3-isoxazoline intermediate. Meanwhile, in the selective formation of 4-isoxazolines, hydride attack at the C5 atom may be obstructed by steric hindrance from the 5-aryl substituent.

Catalytic asymmetric hydrogenation of quinoline carbocycles: unusual chemoselectivity in the hydrogenation of quinolines.

The reduction of quinolines selectively took place on their carbocyclic rings to give 5,6,7,8-tetrahydroquinolines, when the hydrogenation was conducted in the presence of a Ru(η(3)-methallyl)2(cod)-PhTRAP catalyst. The chiral ruthenium catalyst converted 8-substituted quinolines into chiral 5,6,7,8-tetrahydroquinolines with up to 91 : 9 er.

Catalytic asymmetric hydrogenation of pyrimidines.

The asymmetric hydrogenation of pyrimidines proceeded with high enantioselectivity (up to 99% ee) using an iridium catalyst composed of [IrCl(cod)]2, a ferrocene-containing chiral diphosphine ligand (Josiphos), iodine, and Yb(OTf)3 (cod = 1,5-cyclooctadiene). The chiral catalyst converted various 4-substituted pyrimidines into chiral 1,4,5,6-tetrahydropyrimidines in high yield. The lanthanide triflate is crucial for achieving the high enantioselectivity as well as for activating the heteroarene substrate.

Catalytic asymmetric hydrogenation of 3-substituted benzisoxazoles.

A variety of 3-substituted benzisoxazoles were reduced with hydrogen using the chiral ruthenium catalyst, {RuCl(p-cymene)[(R,R)-(S,S)-PhTRAP]}Cl. The ruthenium-catalyzed hydrogenation proceeded in high yield in the presence of an acylating agent, affording α-substituted o-hydroxybenzylamines with up to 57% ee. In the catalytic transformation, the N-O bond of the benzisoxazole substrate is reductively cleaved by the ruthenium complex under the hydrogenation conditions. The C-N double bond of the resulting imine is saturated stereoselectively through the PhTRAP-ruthenium catalysis. The hydrogenation produces chiral primary amines, which may work as catalytic poisons, however, the amino group of the hydrogenation product is rapidly acylated when the reaction is conducted in the presence of an appropriate acylating agent, such as Boc2O or Cbz-OSu.

Intramolecular SN'-type aromatic substitution of benzylic carbonates at their para-position.

The benzylic carbonates, which connect with an active methine through an o-phenylene tether at their meta-position, are cyclized by Pd(η(3)-C(3)H(5))Cp-S-Phos catalyst, yielding 3-methyl-9,10-dihydrophenanthrenes. In the catalytic cyclization, the internal nucleophile attacks not the ortho-carbon but the para-carbon of the benzylic ester. The [3 + 2] cycloaddition of m-(silylmethyl)benzyl carbonates with alkylidene malonates was developed from the palladium-catalyzed intramolecular S(N)'-type aromatic substitution.

Catalytic asymmetric hydrogenation of N-Boc-imidazoles and oxazoles.

Substituted imidazoles and oxazoles were respectively hydrogenated into the corresponding chiral imidazolines and oxazolines (up to 99% ee). The highly enantioselective hydrogenation was achieved by using the chiral ruthenium catalyst, which is generated from Ru(η(3)-methallyl)(2)(cod) and a trans-chelating chiral bisphosphine ligand, PhTRAP. This is the first successful catalytic asymmetric reduction of 5-membered aromatic rings containing two or more heteroatoms.

Palladium-catalyzed [4 + 2] cycloaddition of o-(silylmethyl)benzyl esters with ketones: an equivalent to oxo-Diels-Alder reaction of o-xylylenes.

o-(Silylmethyl)benzyl carbonates reacted with various electron-deficient ketones in the presence of a palladium catalyst, affording the [4 + 2] cycloaddition products, isochromanes, in high yields. The palladium-catalyzed cycloaddition is equivalent to the oxo-Diels-Alder reaction of o-xylylene with ketones. The regioselectivities were extraordinarily affected by the structures of the o-xylylene precursors and ketones. The unusual regiochemistry may support two competitive reaction pathways in the catalytic reaction.

Fluorescence and chemiluminescence properties of indolylmaleimides: experimental and theoretical studies.

Various indolylmaleimides (IMs) were synthesized, and their fluorescence (FL) and chemiluminescence (CL) were measured. The substitution at the 2-position of the indole ring and the 3- or 4-position of the maleimide moiety caused an obvious change in the FL and CL of the IMs. An almost on-off switching of the FL of the IMs was observed. The intramolecular charge transfer from the indole moiety to the maleimide moiety occurred in 3-(1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrroledione. In the FL of the IMs, CASPT2 calculations showed deprotonation of the NH group of the indole ring and the maleimide moiety at the excited state. The C[double bond, length as m-dash]C bond in the maleimide moiety was needed for strong CL in the IMs without substitution at the 2-position of the indole ring. The relationships between the FL or CL properties and the structures of the IMs were clarified. These results provide significant information on the rational design of IMs as FL and CL probes.

[4+2] cycloaddition of o-xylylenes with imines using palladium catalyst.

The cycloaddition of o-(silylmethyl)benzylic carbonates with imines proceeded in the presence of the Pd(eta(3)-C(3)H(5))Cp-DPPPent catalyst, affording the tetrahydroisoquinolines in good to high yields. The reaction rate was remarkably increased by a fluoride additive. In the catalytic cycloaddition, the palladium(0) reacted with the benzylic substrate to form 2-palladaindane, which works as an o-xylylene equivalent. The catalytic reaction is equivalent to the hetero-Diels-Alder reaction of o-xylylene with imines.

Nickel-catalyzed formation of a carbon-nitrogen bond at the beta position of saturated ketones.

Gone fishing: When propiophenone and related ethyl ketones are treated with morpholine in the presence of K(3)PO(4), chlorobenzene, and [Ni(cod)(2)]/PMe(3) catalyst, a carbon-nitrogen bond is formed selectively at the beta position (see scheme; cod = cycloocta-1,5-diene). Secondary amines were employed as substrates to give the corresponding beta-enaminones.

Benzyl protection of phenols under neutral conditions: palladium-catalyzed benzylations of phenols.

Benzyl protection of phenols under neutral conditions was achieved by using a Pd(eta3-C3H5)Cp-DPEphos catalyst. The palladium catalyst efficiently converted aryl benzyl carbonates into benzyl-protected phenols through the decarboxylative etherification. Alternatively, the nucleophilic substitution of benzyl methyl carbonates with phenols proceeded in the presence of the catalyst, yielding aryl benzyl ethers.

Suzuki-Miyaura coupling of diarylmethyl carbonates with arylboronic acids: a new access to triarylmethanes.

Suzuki-Miyaura coupling of diarylmethyl carbonates with arylboronic acids proceeded in the presence of [Pd(eta3-C3H5)Cl]2-DPPPent (1,5-bis(diphenylphosphino)pentane) catalyst, yielding a variety of triarylmethanes.

Catalytic asymmetric hydrogenation of 2,3,5-trisubstituted pyrroles.

Catalytic asymmetric hydrogenation of N-Boc-protected pyrroles proceeded with high enantioselectivity by using a ruthenium catalyst modified with a trans-chelating chiral bisphosphine PhTRAP. The ruthenium catalyst prepared from Ru(eta3-methallyl)2(cod) and (S,S)-(R,R)-PhTRAP in the presence of triethylamine was the most enantioselective for the asymmetric hydrogenation of methyl pyrrole-2-carboxylate, giving the desired (S)-proline derivative with 79% ee in 92% yield. Moreover, 2,3,5-trisubstituted pyrroles bearing a large substituent at the 5-position were hydrogenated with 93-99.7% ee. The asymmetric reduction of 4,5-dimethylpyrrole-2-carboxylate gave only all-cis isomer and created three chiral centers with high degree of stereocontrol in a single process. This is the first highly enantioselective reduction of pyrroles.

Bisindolylmaleimides with large Stokes shift and long-lasting chemiluminescence properties.

Various bisindolylmaleimides have fluorescence emission maxima wavelengths longer than 500 nm, large Stokes shifts longer than 200 nm, different fluorescence emission wavelengths at an excitation wavelength of 365 nm, and a long-lasting chemiluminescence. The expansion of the pi-conjugation, the pi-bond electronic structure, and oxidation of the C=C bond at the 2,3-position of the maleimide moiety are crucial for producing these fluorescence and chemiluminescence properties.