三野 孝

Phosphine-free hydrazone such as 1c was found to be an efficient ligand for the copper-catalyzed Goldberg-type N-arylation of amides and Ullmann-type N-arylation of azoles with aryl halides under mild conditions. A variety of N-arylamides and N-arylazoles were synthesized in good to high yields.

A photosensitized reaction was performed using molecular chirality, which was generated and amplified by the spontaneous crystallization of achiral coumarincarboxamide. The molecular chirality was retained in a cold solution caused by slow racemization and was transferred to optically active products by a photosensitized 2 + 2 cycloaddition reaction with high enantiomeric excesses.

2-Quinolone-4-carboxamide derived from (S)-proline, which exists as a mixture of two diastereomers before crystallization, converged to a single diastereomer by crystallization (CIDT), and the homochirality was transferred by a intermolecular 2 + 2 photocycloaddition reaction with high optical activity.

The asymmetric acylation of meso-2-substituted-1,3-propanediols by using an amphoteric chiral dinuclear zinc catalyst is described. It is has been demonstrated that both 2-alkyl- and 2-aryl-1,3-propanediols can be desymmetrized in high yields and enantioselectivities by using the same family of ligands. Given that both antipodes of the chiral catalyst are available, both enantiomers of the desymmetrized product can be obtained from the same starting material. The synthetic utility of the desymmetrized products has been demonstrated by the synthesis of several chiral building blocks with high enantiomeric purities.

N-Phenyldiethanolamine (1f) is an efficient ligand for zinc-catalyzed transesterification of alcohols with vinyl acetate (R-3 = Me) at room temperature. In the case of using other vinyl esters (R-3 = Et, n-Pr, Ph), the corresponding products were easily obtained in the presence of pyridine-type ligand 2 instead of aminoalcohol 1f. (c) 2007 Elsevier B.V. All rights reserved.

An asymmetric SNAr reaction was performed by using molecular chirality generated and amplified by the spontaneous crystallization of achiral naphthamides; the chirality was retained in a cold solution, caused by slow racemization, and was transferred to stable axially chiral materials with high enantiomeric excesses.

Naphthamides derived from L-proline, which exist as a mixture of several diastereomers in solution, converged to single diastereomer by crystallization, and the conformational transformation was controlled after the crystals were dissolved in the solvent at low temperature, where the frozen conformation was retained long enough for subsequent asymmetric reaction.

Intramolecular cyclization of 3-hydroxy acids was investigated using iodine as a catalyst under solvent-free conditions. The reaction proceeded to completion in the heterogeneous system. Lactones were obtained by intramolecular cyclization of 3-hydroxy acids. Propella lactone (11-oxatricyclo[4.4.3.0(1,6)]tridecan-12-one) was conveniently synthesized from 3-hydroxy acid ((6-hydroxyspiro[4.5]dec-6-yl)acetic acid) in 88% yield with carbon skeleton rearrangement. Spiro lactones and bicyclic lactones were also obtained from the corresponding 3-hydroxy acids in yields of over 75%. The most suitable reaction conditions were a temperature of 80 degrees C, a molar ratio of 3-hydroxy acid:iodine = 1:0.1, and a time period of 6 h. In addition, terpenic lactones were efficiently synthesized from the corresponding 3-hydroxy acids, derived from (+)-camphor, (-)-fencone, and (-)-pulegone, with skeleton rearrangement. The yield of the solvent-free reaction was as high as that of the corresponding reaction in solution.

Palladium/copper-catalyzed Sonogashira cross-coupling reaction of aryl halides with a variety of terminal alkynes under amine-free conditions in dimethylformamide (DMF) at 80 degrees C gave internal arylated alkynes using PdCl2(MeCN)(2) with phosphine-free hydrazone 2a as a ligand and CuI as the cocatalyst in good yields. We also found PdCl2/hydrazone ligand 1d in PhMe at 80 degrees C was a phosphine-free efficient catalyst system for a Hiyama cross-coupling reaction of aryl bromides with aryl(trialkoxy)silanes in good yields.

Optically active hydrazone and imine were found to act as effective ligands for enantio selective addition of diethylzinc to aldehydes. This reaction provided optically active secondary alcohols with ee up to 71%. (c) 2006 Elsevier B.V. All rights reserved.

Glyoxal bishydrazones 1 and pyridyl-hydrazone 2b were prepared and examined as a ligand for the Mizoroki-Heck cross-coupling reaction of aryl halides and olefin. We found that PdCl2(MeCN)(2)/hydrazone ligand 1e was a phosphine-free efficient catalyst system for a variety of substrates to produce the Mizoroki-Heck coupling products in good yields.

N-Aryl indoline-type aminophosphines 1a-c were obtained in good yields by a nucleophilic aromatic substitution (SNAr) reaction followed by silane reduction. Aminophosphine 1d was also prepared from 2,3- difluorobenzaldehyde (4) via dimethylhydrazone. Optical resolution of C(aryl)-N(amine) bond atropisomers was achieved using (5)-(+)-di-μ- chlorobis[2-[(dimethylamino)ethyl]phenyl-C2,N]dipalladium-(II) ((S)-10). The determination of absolute configuration and the investigation of the rotation barrier for C(aryl)-N(amine) bond axial stability of an aminophosphine 1 are described. Finally, the ability of the chiral phosphine ligand 1 is demonstrated in a catalytic asymmetric reaction, such as a palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate (up to 95% ee). © 2006 American Chemical Society.

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (5) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of chiral pyridyl-hydrazone ligands such as 2c with moderate enantioselectivities (up to 67% ee).

X-ray crystallographic analysis and the photochemical aspects of N,N-diallylcoumarincarboxamides were investigated. Irradiation of the corresponding amides promoted stereoselective intramolecular cyclobutane formation exclusively. The solid-state photoreaction of the coumarinamide without substituent on the 4-position proceeded in a crystal-to-crystal manner. On the other hand, photolysis of the amide possessing a methyl group at the 4-position also effected 2+2 cycloaddition; however, the reaction proceeded much slower. The difference in the reactivity was explainable on the basis of the molecular conformation in the crystal lattice. (c) 2006 Elsevier Ltd. All rights reserved.

A series of chiral aminophosphine ligands with N, N-disubstituted 2-diphenylphosphinoaniline backbone are designed and readily prepared from (R)-2-(methoxymethyl)pyrrolidine or (S)-prolinol. The reactivity and selectivity in the palladium-catalyzed asymmetric allylic alkylation (AAA reaction) of 1,3-diphenyl-2-propenyl acetate with a dimethyl malonate-BSA-LiOAc system using these chiral ligands are evaluated. Furthermore, chiral fluorous aminophosphine bearing two fluo rous ponytails was prepared from (S)-prolinol. Chiral fluorous palladium catalyst from this ligand was easily reused in palladium-catalyzed AAA reaction with good enantipselectivity.

Quaternary chiral carbons were effectively generated from tertiary chiral carbons via photochemical intramolecular β-hydrogen abstraction reaction of thioimides involving the highly-controlled chiral-memory effect. © The Royal Society of Chemistry 2006.

Chiral fluorous aminophosphine 4c bearing two fluorous ponytails was prepared from (S)-prolinol and applied to palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (7) with a dialkyl. malonate-BSA-LiOAc system with high enantioselectivities (up to 97% ee). Results indicated that the chiral fluorous palladium catalyst from ligand 4c was easily separated from the reaction mixture by simple solid/liquid separation and could be reused up to five times.

Commercially available, inexpensive N-phenyldiethanolamine (6) is an efficient ligand for zinc-catalyzed transesterification. The use of 6/Et2Zn for reactions between various alcohols and vinyl acetate at room temperature produced the desired products in good yields. (c) 2005 Elsevier Ltd. All rights reserved.

N,N-Diisopropylcarbamoylisatin showed polymorphism and was crystallized into two different space groups, chiral P2(1)2(1)2(1) and racemic P2(1)/c from the solvent; the polymorphism could be controlled by crystallization from the melt using the difference of melting points. (c) 2005 Elsevier Ltd. All rights reserved.

Chiral diaminophosphines 4 were prepared from (S)-prolinol-derived aminophosphine oxide 5 by bromination with ring expansion followed by amination with ring contraction and reduction, using trichlorosilane. In the presence of 4 as ligand, palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (11) with a dialkyl malonate-BSA-LiOAc system was successfully carried out with good enantioselectivities (up to 98% ee).

Glyoxal bis(N-methyl-N-phenylhydrazone) (1) and its related compounds such as 2-pyridine-carboxaldehyde N-methyl-N-phenylhydrazone (3) were prepared and examined as ligands for the Suzuki-Miyaura cross-coupling reaction of aryl halides and arylboronic acids. We found phosphine-free catalysts, such as Pd(OAc)(2)/hydrazone ligand 1 or 3, to be efficient catalysts for a variety of substrates to produce the coupling products in good yields.

Synthesis of optical active compounds from achiral or racemic materials is one of the most impressive studies in organic chemistry. Here we provide two new technique of generation of optical activity without anyl outside chiral source. One is the breaking of chiral symmetry of axially chiral materials via racemization-preferential crystallization method. Another involves the asymmetric reaction using the frozen chirality generated by chiral crystallization of achiral materials.

A series of optically active 1,4-aminoalcohols were synthesized from the corresponding lactones, which were prepared from (+)-camphor and (—)-fenchone, via hydroxy amides. The addition reactions of diethylzinc to aldehydes using the 1,4-aminoalcohols as chiral catalysts were investigated. 1,4-Aminoalcohol catalysts derived from (+)-camphor resulted in secondary (S)-alcohols as the major product. The 1,4-aminoalcohols bearing two propyl groups achieved the highest enantioselectivity the enantiomeric excess was 95%. 1,4-Aminoalcohol catalysts derived from (—)-fencone resulted in secondary (R)-alcohols as the major product. In the chiral 1,4-aminoalcohols from (—)-fencone, the alcohol containing a morpholine structure appended to the amino group possessed the highest enantioselectivity with an enantiomeric excess of 79%. © 2005, Japan Oil Chemists' Society. All rights reserved.

(Chemical Equation Presented) Frozen chirality: Achiral naphthamide 1 can be crystallized to give chiral 1*, whose chiral molecular conformation is retained ("frozen") after the crystals are dissolved in cold THF. Asymmetric photocycloaddition of 1* with 9-cyanoanthracene (9-CNAN) in solution gives cycloadduct 2 with high enantioselectivity. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

A series of novel chiral aminophosphine ligands are designed and readily prepared from (S)-prolinol. The reactivity and selectivity in the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with a dimethyl malonate-BSA-LiOAc system using these chiral ligands are evaluated, and the structural elucidation of ligands and palladium complex is also conducted. Moreover, a series of trialkylsilylated chiral aminophosphine ligands are prepared and applied to palladium-catalyzed asymmetric allylic alkylation (up to 98% ee).

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of chiral phosphine-hydrazone ligands such as 3a in good yields with good enantioselectivities (up to 84% ee). (C) 2004 Elsevier B.V. All rights reserved.

Irradiation of a benzene solution of 2-alkoxy-3-cyanopyridines in the presence of 2-cyanofuran gave 4+4 photoadducts in good yields, and the structure was established by X-ray single crystal analysis. (C) 2004 Published by Elsevier Ltd.

Reaction of the chiral crystals of the achiral amides with n-butyllithium in toluene at -80 degreesC gave optically active alcohols in 17-84% ee.

2-(1-indolinyl)benzaldehyde dimethylhydrazones are prepared by nucleophilic aromatic substitution of the corresponding 2-fluorobenzaldehyde dimethylhydrazones with lithiated indoline in good yields.

The existence of 3 as a pair of stable atropisomers has been demonstrated analytically through chiral phase LC-CD investigations. Resolution of 3d was achieved by preparative chiral HPLC. Finally, the ability of the first C(aryl)-N(amine) axially chiral phosphine ligand 3d is demonstrated in a catalytic asymmetric reaction. (C) 2003 Elsevier Ltd. All rights reserved.

New type chiral ligands 3, which have a chiral carbon center and stable C(aryl)-N(amine) axial chirality, were prepared from chiral prolinol-derived aminophosphine oxide 4. Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (6) with a dimethyl malonate-BSA-LiOAc system was successfully carried out in the presence of 3d resulting in a good yield with good enantioselectivity (up to 95% ee). (C) 2003 Elsevier Science Ltd. All rights reserved.

Glyoxal bis(methylphenylbydrazone) 1 was prepared and examined as a ligand for the Suzuki-Miyaura cross-coupling reaction of aryl bromides and arylboronic acids. We found pbosphine-free catalyst, such as Pd(OAc)(2)/hydrazone ligand 1 to be an efficient catalyst for a variety of substrates to produce the coupling products in good yields at room temperature.

Chiral hydrazone ligands 2 are easily accessible in good yields by nucleophilic phosphanylation of corresponding orthofluorobenzaldehyde SAMP hydrazone derivatives with KPPh2. Palladium-catalyzed asymmetric allylic alkylation of 1,3diphenyl-2-propenyl acetate (6) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of chiral hydrazone ligands 2g in high yields with high enantioselectivities. (C) 2002 Elsevier Science B.V. All rights reserved.

A dinuclear asymmetric zinc catalyst generated by mixing a 2:1 ratio of diethylzinc and 2,6-bis[5-2-diarylhydroxy methyl-1-pyrrolidinyl]-4-methylphenol has been contrasted with enzymes for the desymmetrization of some meso diols. The best ligand has a p-biphenylyl group as the aromatic substituent defining the chiral space. A series of 2-substituted propanediols were examined. The best acyl transfer agent proved to be vinyl benzoate. Diacylation normally did not occur. The phenyl substituted substrate gave 91-95% ee which compares favorably with the best ee of 92% reported for an enzymatic desymmetrization. The methyl substituted substrate gave significantly better results with the dinuclear zinc catalyst (89% yield, 82% ee) as compared to the best enzymatic esterification (70% yield, 60% ee). One case of a 1,4-diol, cis-1,2-bis(hydroxymethyl) cyclohexane, also gave much better results with the dinuclear zinc catalysts (93% yield, 91% ee) as compared to the reported enzymatic process (44% yield, 7% ee). A model to rationalize the results is presented. Copyright © 2003 American Chemical Society.

Asymmetric synthesis using frozen chirality generated by spontaneous crystallization was performed. Achiral asymmetrically substituted imide with a tetrahydronaphthyl group on the nitrogen atom crystallized in a chiral fashion, with space group P2(1)2(1)2(1). The molecular chirality generated by spontaneous crystallization was retained in cold THF. The half-life determined on the basis of decreasing optical activity followed by CD spectrometer was 7.8, 33.1, and 150.0 min at -20, -30, -40 degreesC, respectively. The energy barrier (DeltaG*) of racemization was calculated with the temperature dependence of the kinetic constant to be 18.24-18.36 kcal mol(-1) at 233-253 K. The memorized frozen chirality was transferred to permanent optically active alcohols by nucleophilic addition with n-buthyllithium.

Irradiation of a benzene solution of 3-cyano-2,6-dimethoxypyridine in the presence of ethyl vinyl ether (EVE) gave 1:1 photoadducts, 3-cyano-5-ethoxy-2,8-dimethoxy-4,5-dihydroazocine, in good yields, whose structure was established by X-ray single-crystal analysis. The photoadduct was produced via cycloaddition between the C3-C4 position of the pyridine derivatives and an alkene chromophore. On the other hand, 3-cyano-2,6-dimethoxy-4-methylpyridine cycloadds to EVE at the C2-C3 position of the pyridine ring upon irradiation. The difference is explained on the basis of the steric effect.

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of a new chiral prolinol-derived aminophosphine ligand (3e) in good yield with good enantioselectivity (up to 96% ee).

Photolysis of axially chiral monothiosuccinimides in the presence of diphenylethylene gave spirothietanes effectively, where the cycloaddition took place diastereoselectively by way of the steric effect of the ortho-substituent on the phenyl ring.

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (3) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of planar chiral phosphine-hydrazone ligands such as 2a in good yields with good enantioselectivities (up to 96% ec). (C) 2002 Elsevier Science B.V. All rights reserved.

No outside source of chirality was needed to resolve the racemate of an axially chiral pyrimidinone (see scheme). Crystallization at high temperatures gave optically active material in up to 73 % ee. The resolved product could be reduced with NaBH4with high enantioselectivity.

Irradiation of a benzene solution containing 2-alkoxynicotinic acid esters (0.02 M) and furan (0.2 M) resulted in the formation of cage-type adducts in 73-84% yield. The structure of the adducts was established by X-ray crystallographic analysis. The mechanism involving 4pi+4pi photocycloaddition between the pyridine ring and furan was postulated. Two diastereomeric 4pi+4pi adducts were detected as intermediates in the H-1 NMR spectroscopy, when the solution was irradiated in the presence of diene as a triplet quencher. (C) 2002 Elsevier Science Ltd. All rights reserved.

Irradiation of a benzene solution of 2-alkoxynicotinic acid alkyl esters gave cage-type photodimers in good yields, the structure of which was established by X-ray single-crystal analysis. The maximum quantum yield was 8.0 x 10(-2) when a 5.0 M (almost neat) solution was used. Photolysis of phenyl 2-methoxynicotinate promoted photo-Fries rearrangement to give 1,3- and 1,5-rearranged products. Excimer emission of methyl 2-methoxynicotinate was observed at 77 K.

Photochemistry of aromatic compounds has received much attention from both the mechanistic and synthetic perspectives, and the intra- and intermolecular photochemical cycloaddition of carbon aromatics is well documented. Furthermore, the photocycloaddition of alkenes to benzene derivatives is also a useful method for synthesizing natural products. However, in contrast, the photocycloaddition reaction of aza-aromatics, such as pyridines, pyridazines, pyrazines, or pyrimidines, is an underdeveloped area of research. We found that the induction of suitable substituents to appropriate position of aza-aromatic ring made the photoreactivity considerably high. Many new photochemical reactions for pyridine derivatives have been found in photodimerization, photocycloaddition with alkenes, furan, benzofuran or cyanonaphthalene. These reactions provide not only new photochemical aspect of aza-aromatics, but also useful synthetic method of polycyclic heterocycles.

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate 7a using a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of new chiral aminophosphine ligands such as 4 in good yields with good enantioselectivities (up to 96 4, e.e.). (C) 2001 Elsevier Science Ltd. All rights reserved.

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (8a) with a dimethyl malonate-BSA-LiOAc system has bren successfully carried out in the presence ol novel chiral phosphine-oxazinane ligands such as 5b in good yields with good enantioselectivities (up to 95% eel. (C) 2001 Elsevier Science Ltd. All rights reserved.

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate IS with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of new chiral aminophosphine ligands 1-5 in good yields with good enantioselectivities (up to 85% e.e.). (C) 2001 Elsevier Science Ltd. All rights reserved.

Achiral N-methacryloylthiobenzanilide formed (Z,E)-conformation of the imide moiety and crystallized in a chiral fashion. The solid-state photoreaction gave optically active beta -lactam. The dynamic molecular rearrangement for cyclization was elucidated on the basis of direct comparison of the absolute configuration of both the starting material and the photoproduct. Crystal-to-crystal transformation was observed in the photoreaction of the (E,E)-conformation of N-isopropyl-N-tigloylthiobenzamide, which needs small atomic rearrangement for the cyclization and gave thietane stereo- and chemo-selectively. (C) 2001 Elsevier Science Ltd. All rights reserved.