三宅 由寛

Our previously disclosed ruthenium-catalyzed carbon-carbon bond forming reactions between propargylic alcohols and alkenes via an allenylidene-ene type pathway have been successfully applied to an enantioselective intramolecular cyclization for a variety of chiral heterocycles such as chromane, thiochromane, and 1,2,3,4-tetrahydroquinoline derivatives (up to 99% ee) by use of a suitable optically active diruthenium complex as a catalyst. The methodology described in this paper becomes a novel synthetic approach to chiral heterocycles, the structures of which are widely found in many natural and biologically active compounds.

Ruthenium-catalyzed intramolecular cyclization of 3-butyne-1,2-diols affords the corresponding substituted furans in good to high yields. This catalytic reaction is proposed to proceed via ruthenium-allenylidene complexes as key intermediates.

The development of optically active chiral ligands, ferrocenyloxazolinylphosphines (FOXAPS), and their application to catalytic asymmetric reactions are reviewed. FOXAPs have been prepared in high yields from the corresponding chiral oxazolinylferrocenes via diastereoselective lithiation followed by quenching with chlorodiphenylpbosphine. They work quite effectively as chiral ligands for a variety of transition-metal-catalyzed asymmetric reactions such as hydrosilylation and transfer hydrogenation of ketones and imines, kinetic resolution of alcohols, carbon-carbon bond-forming reactions and ring-opening reactions.

Ruthenium-catalyzed carbon-carbon bond forming reactions between propargylic alcohols and acyclic and cyclic 1,3-conjugated dienes give the corresponding dienyne compounds in good to high yields. Only the use of thiolate-bridged diruthenium complexes promotes the catalytic reactions, where a ruthenium-alkynyl complex, a resonance structure of a ruthenium-allenylidene complex, works as a key intermediate. This carbon-carbon bond forming reaction is considered to proceed via a stepwise reaction pathway. The finding described in this article reveals another novel catalytic reactivity of chalcogenolate-bridged diruthenium complexes.

Novel ruthenium-catalyzed vinylic substitution reactions of vinylic trifluoromethanesulfonates with nucleophiles such as cyclic 1,3-diketones and alcohols have been found to give the corresponding vinylic-substituted products in good to high yields. This catalytic reaction is considered to be a new type of vinylic substitution reaction. Reactions of -ketoacetylenes with alcohols have also been found to afford the corresponding vinylic ethers in good yields. These catalytic reactions can be explained to proceed by proposing ruthenium-butatrienylidene complexes as key intermediates. We believe that this finding will open up a further aspect of the chemistry of metal-cumulenylidene complexes.

A novel hetrotrinuclear complex composed of two ferrocenium-ion moieties and copper complex of 2-aminotropones showed relatively strong intramolecular ferromagnetic coupling in the solid states owing to spin polarization mechanism.

Ruthenium-catalyzed enantioselective propargylation of indoles with propargylic alcohols affords the corresponding beta-propargylated indoles in good yields with a high enantioselectivity (up to 95% ee). A remarkable effect of the nature of the N-substituent of indoles is observed for the enantioselectivity of the propargylated indoles. The preparative method described in this paper may provide a novel protocol for asymmetric Friedel-Crafts alkylation of indoles using propargylic alcohols as a new type of electrophiles.

We have prepared a novel pseudorotaxane molecule which works as a chiral bidentate ligand having a phosphine moiety in an axle and a phosphite moiety in a wheel as two coordination sites and applied it successfully to the rhodium-catalyzed enantioselective hydrogenation of enamides (up to 96% ee). To the best of our knowledge, this is the first successful example of the use of the pseudorotaxane molecule as a chiral ligand for homogeneous transition-metal-catalyzed asymmetric reactions.

Recent development of optically active chiral ligands, ferrocenyloxazolinylphosphines (FOXAP), and their application to catalytic asymmetric reactions are reviewed. FOXAP have been prepared in high yields from the corresponding chiral oxazolinylferrocenes via diastereoselective lithiation followed by quenching with chlorodiphenylphosphine. They work as chiral ligands quite effectively for a variety of transition metal-catalyzed asymmetric reactions such as hydrosilylation and transfer hydrogenation of ketones and imines, kinetic resolution of alcohols, carbon-carbon bond forming reactions and ring-opening reactions.

Treatment of a chloride-bridged tetraruthenium complex with tetramethyldiphoshine and tetraphenyldiphosphine affords a different type of diphosphine-bridged diruthenium complexes, which are further transformed into the corresponding cationic complexes by treatment with silver trifluoromethanesulfonate. Some diphosphine-bridged diruthenium complexes show a catalytic activity toward the quantitative cyclotrimerization of ethyl propiolate to two regioisomeric benzene derivatives.

Ruthenium-catalyzed efficient preparation of the conjugated enynes can be carried out in the reactions of 1-cyclopropyl-2-propyn-1-ols with nitrogen- and oxygen-centered nucleophiles such as anilines and water in the presence of a catalytic amount of sulfur-bridged diruthenium complexes. The use of such complexes as catalysts realizes the completely stereoselective preparation of tri- and tetrasubstituted conjugated enynes, where ruthenium-allenylidene complexes work as key intermediates. The direct attack of nucleophiles on a cyclopropane ring connected to an allenylidene ligand is a key step to obtain the enynes stereoselectively.

The deracemization of secondary benzylic alcohols proceeds successfully by a two-step process with the appropriate combination of two different ruthenium complexes for catalysis in the first oxidation and second reduction steps. The sequential catalytic system provides a novel approach to obtaining optically active alcohols, including diols, in high yields with excellent enantioselectivity (up to 95% ee), in contrast to the conventional kinetic resolution of racemic alcohols.

The iridium-catalyzed hydrosilylation of alkynes in the presence of 4,4,5,5'-tetramethylbiphosphinine (tmbp) has been explored. The hydrosilylation of alkynes in the presence of tmbp proceeds effectively to give beta-(E)-vinylsilanes highly selectively in moderate to high yields, whereas a similar hydrosilylation in the absence of tmbp produces beta-(Z)-vinylsilanes selectively. The stereoselectivity of these reactions suggests the importance of the electron-withdrawing properties of tmbp coordinated to iridium.

An efficient method for the homocoupling of aryl halides by electron-transfer oxidation of Lipshutz cuprates (Ar2Cu(CN)Li-2) with organic electron acceptors is disclosed. Thus, various types of Lipshutz cuprates are prepared by successive treatment of aryl or heteroaryl bromides with tert-butyllithium and CuCN. The electron-transfer oxidation of Lipshutz cuprates with p-benzoquinones proceeds smoothly to afford the corresponding homocoupling products in moderate to good yields. Furthermore, it can be applied to the construction of either thiophene- or benzene-fused 10-membered ring cyclophanes. For the synthesis of 10-membered cyclophanes, the linear C-Cu-C structure of Lipshutz cuprates should be maintained in the dimetallacyclic intermediates, producing the large ring cyclophanes efficiently. The X-ray analysis of the cyclophanes reveals that the difference in the bridging atoms results in the different conformations of the macrocyclic rings. Thus, the silicon-bridged cyclophane 5a adopts a D-2-symmetric structure with a twisted rhombic arrangement of four thiophene rings, whereas the methylene- and oxygen-bridged cyclophanes 5b and 5c possess C2h- and C-2-symmetric structures with chair- and boatlike conformations, respectively. The H-1 NMR spectrum of C-2-symmetric 5c is temperature- dependent, and the activation energy (Delta G double dagger) for the conformational change is 10.1 kcal/mol.

Nonaphenylene and its hexaalkyl derivatives have been synthesized using electron-transfer oxidation of Lipshutz cuprates with duroquinone. Oxidation of the Lipshutz cuprate derived from dibromo-o-terphenyl in THF produced nonaphenylene in moderate yield, whereas the similar oxidation of the Lipshutz cuprate derived from diiododiethyl-o-terphenyl in ether afforded the corresponding nonaphenylene and dodecaphenylene. Furthermore, oxidation of Lipshutz cuprate derived from diiododibutyl-o-terphenyl only gave the nonaphenylene.

The electron transfer reaction from Lipshutz cuprates, which can be easily prepared from aryl bromides, to 1,4-benzoquinones was found to proceed smoothly, affording either the corresponding homo-coupling products, in modest to excellent yields, or macrocyclic products selectively.

The titled tetraselenanaphthalene derivative (BEDO-TSeN) has been synthesized using the reaction of 1,4-dioxene-2,3-diselenolate with tetraiodo- or tetrabromoethylene. The structure of this tetraselenanaphthalene derivative was confirmed by X-ray analysis. The pi-donor property of this molecule was determined by CV analysis.

Sulfur-bridged octadehydro[20]annulene 1c annelated with two TTF rings was synthesized and its multi-functional proper: ties were ascertained. The annulene exhibits paratropicity, solvato chromism, electrochromism and multi-redox potentials in solution, and its cation radical in the solid state shows self-association and electric conductivity.

A simple and efficient synthesis of tribenzohexadehydro[12]annulene and its derivatives was carried out using coupling reaction of acetylenes with iodoarenes in the presence of catalytic amounts of CuI and PPh3, together with three equivalents of K2CO3 in DMF. This synthetic procedure was applied to the synthesis of a large annulenoannulene derivative.

The ring cleavage of 4,5-ethylenedioxy-1,3-dithiole- and -1,3-diselenole-2-thiones, followed by the reaction with 4,5-bis(methoxycarbonyl)-1,3-diselenole-2-one took place under the phosphite-mediated cross-coupling conditions to afford 2-thioxo- and 2-(selenoxomethylidene)-1,3-diselenoles. The structure of 4,5-bis(methoxycarbonyl)-2-(thioxoalkylidene)-1,3-diselenole was confirmed by X-ray analysis.

Cyclic selenoxides having an optically active binaphthyl skeleton work as the reagents for enantioselective oxidation of phosphines to the corresponding phosphine oxides. Treatment of a racemic 2-oxazolin-2-ylferrocenylphosphine with one of the selenoxides in carbon tetrachloride in the presence of phenol affords the corresponding phosphine oxide together with the unreacted starting phosphine, both with moderate enantioselectivities (the phosphine oxide, up to 13% ee; the phosphine, up to 29% ee).

Novel optically active diselenides having a chiral oxazoline have been prepared and the structure of one of them is unambiguously determined by X-ray structural analysis. Treatment of a variety of cyclobutanones with 30% H2O2 in the presence of a catalytic amount of the optically active diselenides in tetrahydrofuran or 1,4-dioxane at 0 degreesC-rt affords the corresponding gamma-lactones in up to 92% yield with up to 19% ee. The enantioselectivity of the product is not yet satisfactory, but this is the first example of asymmetric Baeyer-Villiger oxidation catalyzed by chiral organoselenium compounds.

Reactions of aromatic aldehydes with benzyl bromide or iodide in the presence of a catalytic amount (10 mol%) of a C-2 symmetric sulfide having a binaphthyl skeleton afford the corresponding trans-stilbene oxides in moderate to good yields with moderate enantioselectivities (up to 55% enantiomeric excess). The addition of tetra-n-butylammonium iodide to the catalytic reaction system much improves the yield of the epoxides. (C) 2002 Wiley Periodicals, Inc.

A novel method for the kinetic resolution of racemic secondary alcohols via their enantioselective benzoylation has been explored using CO, Ph3Bi(OAc)(2), a catalytic amount of a chiral Pd(II) complex and AgOAc. In this catalytic system, Ph3Bi(OAc)(2) has been revealed to work better than any other phenylating reagents such as PhB(OH)(2) or PhSnMe3. It has also been disclosed that the planar chirality of optically active oxazolinylferrocenylphosphine (3e) has some positive effect on the enantioselectivity. Satisfactory enantioselectivity has not yet been obtained (up to 48% ee), but this reaction system seems to be interesting from the viewpoint of both asymmetric synthesis and organobismuth chemistry.

A novel method for kinetic resolution of racemic secondary alcohols via their enantioselective benzoylation (up to 48% ee) has been explored using CO, Ph3Bi(OAC)(2), a catalytic amount of chiral Pd(II)-complex and AgOAc.

Treatment of aryl benzyl selenides with [N-(p-toluenesulfonyl)imino]phenyliodinane [TsN=IPh] in the absence or presence of copper(I) salt in toluene or acetonitrile affords the corresponding N-tosylselenimides in 31-46% yield. When the reaction is carried out in the presence of optically active 4,4'-disubstituted bis(oxazoline) as a ligand together with molecular sieves, enantioselective imidation occurs to give optically active N-tosylselenimides and the best result is obtained from benzyl 2-naphthyl selenide (64% yield and 36% ee). Similar treatment of allylic selenides gives the corresponding optically active allylic amides (up to 71% yield and 30%. ee). In the case of diastereoselective imidation, the reaction of diaryl selenides bearing a chiral oxazolinyl moiety with TsN=IPh or Chloramine-T trihydrate [TsN(CI)Na . 3H(2)O] has been successfully carried out to give the corresponding optically active N-tosylselenimides in good yields (up to 97%, isolated yield and 76% de). The absolute configuration around the selenium atom of (4S)-Se-[2-(4-isopropyloxazolin-2-yl)phenyl]-Se-phenyl-N-(p-toluenesulfonyl)selenimide [(4S)-13], obtained by diastereoselective imidation of the corresponding selenide with Chloramine-T trihydrate, has been determined to be S by X-ray crystallographic analysis, from the result of which an ionic reaction pathway involving a chloroselenonium ion intermediate is proposed. (C) 2000 Elsevier Science S.A. All rights reserved.

Optically active oxazolinylferrocenylphosphines have been found to work quite effectively as chiral ligands in nickel(0)-catalyzed cross-coupling reactions of allylic compounds with arylboronic acids, which are known to behave as "hard" nucleophiles. The expected coupling products have been obtained in good yields with moderate enantioselectivities (up to 53% ee). This is the first example of asymmetric allylic substitution using organoboron compounds.

Enantioselective desymmetrization of meso-cyclic disulfides has been investigated on the basis of the desulfurization with chiral phosphines. Chiral tert-aminophosphines enable the desulfurization of a six-membered disulfide, cis-3,6-bis(alkoxycarbonyl)-1,2-dithiane 2, to give an enantiomerically enriched five-membered sulfide, trans-2,5-bis(alkoxycarbonyl)thiolane 5, with up to 36% ee. The desulfurization of a seven-membered disulfide, cis-3,7-bis(alkoxycarbonyl)-1,2-dithiepane 3, with chiral aminophosphines also gives a six-membered sulfide, trans-2,6-bis(alkoxycarbonyl)thiane 6, with up to 30% ee.

Optically active oxazolinylferrocenylphosphines work effectively as chiral P-N ligands in nickel(0)-catalysed cross-coupling reactions of allylic compounds with Grignard reagents, which are known to behave as "hard" nucleophiles, to give the expected coupling products in high yields and high enantioselectivities (30-100% chemical yield and 14-95% ee). These ligands are revealed to be more effective than optically active oxazolinylphenylphosphines which have only a central chirality.

Enantioselective desymmetrization of meso-cyclic disulfides has been investigated on the basis of the desulfurization with chiral phosphines. Chiral tert-aminophosphines enable the desulfurization of a six-membered disulfide, cw-3,6-bis(alkoxycarbonyl)-1,2-dithiane 2, to give an enantiomerically enriched five-membered sulfide, trans-2,5-bis(alkoxycarbonyl)thiolane 5, with up to 36% ee. The desulfurization of a seven-membered disulfide, ds-3,7-bis(alkoxycarbonyl)-1,2-dithiepane 3, with chiral aminophosphines also gives a six-membered sulfide, trans-2,6-bis(alkoxycarbonyl)thiane 6, with up to 30% ee. © The Royal Society of Chemistry 2000.

Optically active oxazolinylferrocenylphosphines have been found to work quite effectively as chiral ligands in nickel(0)-catalyzed cross-coupling reactions of allylic compounds with arylboronic acids, which are known to behave as "hard" nucleophiles. The expected coupling products have been obtained in good yields with moderate enantioselectivities (up to 53% ee). This is the first example of asymmetric allylic substitution using organoboron compounds. © The Royal Society of Chemistry 2000.

lA direct catalytic sulfimidation of l,3-dithianes to the corresponding chiral monosulfimides with N-(p-tolylsulfonyl)imino(phenyl)iodinane (TsN=IPh) using a catalytic amount of copper(I) triflate (CuOTf) and a chiral 4,4'-disubstituted bis(oxazoline) as ligand has been developed. The reaction affords the chiral monosulfimides in good yield and with moderate enantioselectivity (up to 40% ee).

The direct catalytic imidation of various prochiral selenides with TsN=IPh in the presence of CuOTf using chiral 4,4'-disubstituted 2,2'-bis(oxazoline) ligand afforded the corresponding chiral selenimides(similar to 36% ee).