柳澤 章

<title>Abstract</title>A catalytic enantioselective aldol reaction of alkenyl esters with α-keto esters was achieved by using an (R)-BINOL-derived chiral tin dibromide possessing 4-t-butylphenyl groups at the 3- and 3′-positions as a chiral precatalyst in the presence of sodium methoxide and methanol. Optically active aldol products possessing a chiral tertiary carbon were diastereoselectively obtained with up to 92% ee and moderate to high yields, not only from cyclic alkenyl esters, but also from acyclic ones under the influence of the chiral tin methoxide generated in situ.

The Barbier-type propargylation of azo compounds with α,γ-disubstituted propargylic tosylates was achieved by using metallic barium as the promoter. Various propargylated hydrazines (α-adducts) were exclusively synthesized from the corresponding propargylic tosylates and azobenzenes (diaryldiazenes). The thus-obtained propargylic hydrazines were further efficiently converted into propargylic amines by reductive N–N bond cleavage. Benzidine rearrangement of the propargylic hydrazines was also attempted.

© 2017 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim. A catalytic, asymmetric allylation reaction of aldehydes or ketones with allyltrimethoxysilane was achieved by using a BINAP·AgBF4[BINAP = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl] complex as the chiral precatalyst and triethylamine as the base precatalyst in the presence of 2,2,2-trifluoroethanol. Optically active homoallylic alcohols with up to 95 % ee were obtained in moderate to high yields through the in situ generated chiral allyl silver catalyst.

© 2016 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim A catalytic asymmetric O-nitroso aldol reaction of alkenyl trifluoroacetates with nitrosoarenes was achieved by using QuinoxP*·AgOAc [(R,R)-QuinoxP* = (–)-(R,R)-2,3-bis(tert-butylmethylphosphino)quinoxaline] as the chiral precatalyst and N,N-diisopropylethylamine as the base precatalyst in the presence of methanol. Optically active α-aminooxy ketones with up to 99 % ee were regioselectively obtained in moderate to high yields by the in situ generated chiral silver enolates.

© 2016 Georg Thieme Verlag Stuttgart, New York. The Barbier-type allylation of isatin imines with allylic chlorides was achieved by using metallic barium as the promoter. Various α-allylated 3-amino-2-oxindoles were synthesized from the corresponding allylic chlorides and isatin imines. The double-bond geometry of allylic chlorides was retained throughout the reaction. An arylic bromide or iodide functionality of the products was robust to metalation under the optimum reaction conditions.

The enantio- and diastereoselective cross-annulation of cinnamaldehyde (6) and 2,2,2-trifluoroacetophenone (7) was examined to evaluate the performance of newly developed chiral bicyclic imidazolium salts 3 and 4 as catalyst precursors. The reaction proceeded to give desired gamma-lactone 8 with high diastereoselectivities (up to 10/1) and moderate enantioselectivities (up to 71% ee) when the sterically demanding catalyst precursors were used.

A catalytic enantioselective Mannich-type reaction of a cyclohexanone-derived alkenyl trichloroacetate with isatin imines was achieved using an (S)-BINOL-derived chiral tin dibromide possessing a 4-tert-butylphenyl group at 3- and 3-positions as the chiral precatalyst in the presence of sodium methoxide, sodium iodide, and methanol. Optically active 3-alkylated 3-amino-2-oxindoles having up to 90% enantiomeric excess were diastereoselectively obtained in high yields under the influence of the in situ generated chiral tin iodide methoxide.

A couple of planar-chiral ferrocene-fused 4-pyridone derivatives 2a and 2b were synthesized in enantiomerically pure form by scalable asymmetric transformations. Pyridones 2 are versatile precursors to various ferrocene-fused pyridine derivatives, which are useful nucleophilic asymmetric organocatalysts.

The Barbier-type benzylation of azo compounds with benzylic chlorides was achieved by using reactive barium as the promoter. Various benzylic hydrazines were synthesized from the corresponding benzylic chlorides. The thus-obtained benzylic hydrazines were further efficiently converted into benzylic amines by reductive N-N bond cleavage.

A diverse series of chiral bicyclic NHC/Ir complexes were prepared via a previously developed divergent synthesis of chiral imidazolium salts. Among the complexes, 8dz was found to be an excellent catalyst precursor for the Ir-catalyzed asymmetric transfer hydrogenation of ketones. The reaction of ketones with 8dz proceeded smoothly to give corresponding alcohols with high enantioselectivities (up to 98%) and productivities (TON up to 4500).

A catalytic asymmetric aldol reaction of alkenyl trihaloacetates or a gamma,delta-unsaturated delta-lactone with aldehydes or an alpha-keto ester was achieved by using a 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl.silver trifluoromethanesulfonate complex as the chiral precatalyst and N,N-diisopropylethylamine as the base precatalyst in the presence of methanol. Optically active alpha-alkyl beta-hydroxy ketones with enantioselectivities of up to 95?%?ee were diastereoselectively obtained in moderate to high yields through the in situ generated chiral silver enolates.

The synthesis of substituted styrenes 3 and 3-vinylphenols 9 was achieved by ring-closing enyne metathesis (RCEM)/dehydration of 7 and RCEM/tautomerization of 8, respectively. Those methods provide selective access to unique aromatic compounds and solve the problem of regioisomer formation.

A catalytic asymmetric Mannich-type reaction of alkenyl trichloroacetates with aldimines was achieved using SEGPHOS center dot AgOTf as the chiral precatalyst and N,N-diisopropylethylamine as the base precatalyst in the presence of 2,2,2-trifluoroethanol. Optically active beta-amino ketones with up to &gt;99% ee were syn-selectively obtained in moderate to high yields via the in situ generated chiral silver enolates.

The asymmetric α-amination of alkenyl trifluoroacetates with dialkyl azodicarboxylates catalyzed by the DTBM-SEGPHOS·AgOTf complex takes place in the presence of 2,2,2-trifluoroethanol with almost quantitative yield and high ees of up to 97%. © 2014 The Royal Society of Chemistry.

The selective synthesis of substituted 4-vinylindoles by the ring-closing enyne metathesis (RCEM)/dehydration sequence is reported. In contrast with many known methods in which a pyrrole ring is constructed onto a functionalized benzene precursor, this method enables the construction of a benzene ring onto a pyrrole precursor. The RCEM/tautomerization sequence for the synthesis of 7-hydroxy-4-vinylindole is also presented as an application of this method.

Asymmetric catalysis under almost-neutral reaction conditions is key for the efficient synthesis of optically active polar molecules. We have developed catalytic enantioselective reactions of acyclic or cyclic alkenyl esters by using an (S)-BINOL-derived chiral tin-dibromide reagent that possesses a bulky aryl group at the 3 or 3 position as the chiral pre-catalyst in the presence of a sodium alkoxide and an alcohol, in which a chiral tin alkoxide bromide is generated in situ and recycled with the assistance of an alcohol. In this Personal Account, we describe three types of asymmetric transformation that proceed through a chiral tin enolate: 1) The asymmetric aldol reaction of alkenyl esters or unsaturated lactones with aldehydes or isatins; 2) the asymmetric three-component Mannich-type reaction of alkenyl esters and related cycloaddition reactions; and 3) the asymmetric N-nitroso aldol reaction of unsaturated lactones with nitrosoarenes. DOI 10.1002/tcr.201200019

The addition of allylic barium reagents to azo compounds was achieved with high α-regioselectivity. The double-bond geometry of allylic barium reagents was retained throughout the reaction at -78 °C and E- or Z-enriched allylic hydrazines were selectively obtained from the corresponding allylic barium reagents. An allylic hydrazine was efficiently converted into an allylic amine by reductive N-N bond cleavage. © 2012 Georg Thieme Verlag Stuttgart · New York.

A catalytic enantioselective aldol reaction of alkenyl esters with isatins was achieved using an (S)-BINOL-derived chiral tin dibromide possessing a 4-tert-butylphenyl group at 3- and 3'-positions as the chiral pre-catalyst in the presence of sodium methoxide and methanol. Optically active 3-alkylated 3-hydroxy-2-oxindoles having up to 98% ee were diastereoselectively obtained in high yields not only from cyclic alkenyl esters but also from acyclic ones under the influence of the in situ generated chiral tin bromide methoxide.

A catalytic enantioselective cycloaddition reaction of alkenyl trichloroacetates with nitrones was achieved using an (S)-BINOL-derived chiral tin dibromide possessing a 4-trifluoromethylphenyl group at 3- and 3'-positions as the chiral precatalyst in the presence of sodium ethoxide, sodium iodide, and ethanol. Optically active isoxazolidines with up to 95% ee were diastereoselectively obtained in high yields even from aliphatic aldehyde derived nitrones under the influence of the in situ generated chiral tin ethoxide iodide.

Both enantiomers of 2,3-bis(tert-butylmethylphosphino)quinoxaline (QuinoxP*), 1,2-bis(tert-butylmethylphosphino)benzene (BenzP*), and 1,2-bis(tert-butylmethylphosphino)-4,5-(methylenedioxy)benzene (DioxyBenzP*) were prepared in short steps from enantiopure (S)- and (R)-tert-butylmethylphosphine-boranes as the key intermediates. All of these ligands were crystalline solids and were not readily oxidized on exposure to air. Their rhodium complexes exhibited excellent enantioselectivities and high catalytic activities in the asymmetric hydrogenation of functionalized alkenes, such as dehydroamino acid derivatives and enamides. The practical utility of these catalysts was demonstrated by the efficient preparation of several chiral pharmaceutical ingredients having an amino acid or a secondary amine component. A rhodium complex of the structurally simple ligand BenzP* was used for the mechanistic study of asymmetric hydrogenation. Low-temperature NMR studies together with DFT calculations using methyl alpha-acetamidocinnamate as the standard model substrate revealed new aspects of the reaction pathways and the enantioselection mechanism.

Since the first report in 1991 of the regio- and stereoselective allylation of carbonyl compounds with allylic barium reagents, various barium reagents have been utilized in organic transformations. This account focuses on recent examples of barium reagent promoted regio- and stereoselective reactions, such as Barbier-type propargylations, a Reformatsky-type reaction, Michael additions, aldol reactions, Mannich-type reactions, a Friedel-Crafts-type alkylation, and a Diels-Alder-type reaction. 1 Introduction 2 Stoichiometric Use of Barium Reagents 2.1 Selective Propargylation of Electrophiles with Propargylic Bromides Promoted by Reactive Barium 2.1.1 Selective Propargylation of Carbonyl Compounds 2.1.2 Selective Propargylation of Imines 2.1.3 Selective Propargylation of Azo Compounds 2.2 Reformatsky-type Reaction of a-Chloro Ketones with Aldehydes Promoted by Reactive Barium 2.3 Barium Hydride Promoted Synthesis of 1,5-Diketones 2.3.1 Homocoupling of Enones 2.3.2 Cross-Coupling of Enones 3 Catalytic Use of Barium Reagents 3.1 Barium Alkoxide Catalyzed Synthesis of 1,5-Diketones 3.1.1 Reactions of Ketones with Aldehydes 3.1.2 Reactions of Ketones with Enones 3.2 Barium Alkoxide Catalyzed Direct Aldol Reaction 3.3 Barium Alkoxide Catalyzed Direct Mannich-type Reaction 3.4 Chiral Barium Alkoxide Catalyzed Asymmetric Friedel-Crafts-type Alkylation 3.5 Chiral Barium Alkoxide Catalyzed Asymmetric Diels-Alder-type Reaction 4 Conclusion

The selective synthesis of substituted indoles was achieved by the ring-closing olefin metathesis (RCM)/elimination sequence or the RCM/tautomerization sequence of functionalized pyrrole precursors. The RCM/elimination sequence was also applied to double ring closure to yield a substituted carbazole.

A new chiral zinc-amide 2s' was found to be an effective catalyst for the asymmetric addition of diethylzinc to aldehydes 3 through a screening method for asymmetric catalysts, in which two catalytic asymmetric reactions are connected. The chiral zinc catalyst can be readily prepared catalytically from achiral imine 1 by the chiral rhodium-diene complex mediated asymmetric addition of dimethylzinc. (C) 2011 Elsevier Ltd. All rights reserved.

The deleterious effect of ethylene gas on the ring-closing olefin metathesis (RCM) for the formation of 5- to 8-membered rings was investigated. Significant rate differences caused by ethylene gas were observed among the different ring-size formation reactions. Nevertheless, the rate differences can be advantageously utilized for chemoselective RCM.

Tandem ring-closing enyne metathesis (RCEM)/ring-closing olefin metathesis (RCM) of tetraenynes with Grubbs second-generation catalyst, followed by elimination, was found to be a new and efficient synthetic approach to biaryl compounds. A preliminary asymmetric version of this approach, which used homochiral Ru-alkylidene catalysts, is also presented.

A novel reaction involving cyano transfer from benzophenone cyanohydrin to aldehydes and imines was realized by using dibutyltin dimethoxide as a catalyst. Various cyanohydrins and alpha-amino nitriles were obtained in moderate to high yields by this reaction. Ketimines also showed remarkable reactivity as cyano acceptors under conventional reaction conditions. This catalytic reaction was further applied to a three-component condensation reaction of aldehydes, aniline, and benzophenone cyanohydrin in the presence of Drierite (R).

An electron-rich P-stereogenic bisphosphine ligand named "BenzP(star)" was conveniently prepared from o-dibromobenzene and enantiopure tert-butylmethylphosphine-borane. Its rhodium complex exhibited excellent enantioselectivities of up to 99.9% and high catalytic activity of up to 10 000 h(-1) TOE in asymmetric hydrogenations of various functionalized alkenes.

A Barbier-type propargylation of azo compounds with gamma-trialkylsilylated propargylic bromides has been achieved using reactive barium as a low-valent metal in THF. Corresponding propargylated hydrazines (alpha-adducts) were exclusively formed not only from azobenzenes (diaryldiazenes) but also from dialkyl azodicarboxylates. This method is also applicable to gamma-alkylated or gamma-phenylated propargylic bromides, providing the desired propargylated products only.

The preparation of new chiral bicyclic imidazoles 5 and their transformation into imidazolium salts 6 and 7 are reported. The utility of the salts as precursors for chiral N-heterocyclic carbenes was demonstrated by the synthesis of C-N-C pincer Ni-complex 13h, the structure of which was characterized by single-crystal X-ray analysis.

A catalytic enantioselective three-component Mannich-type reaction of alkenyl trichloroacetates, ethyl glyoxalate, and aniline derivatives was achieved using an (S)-BINOL-derived chiral tin dibromide possessing a 4-trifluoromethylphenyl group at the 3- and 3&apos;-positions as the chiral precatalyst in the presence of sodium ethoxide, sodium Iodide, and ethanol. Optically active beta-amino ketones with up to 98% ee were syn-selectively obtained in high yields even from Imines possessing a polar amino group under the influence of the in situ generated chiral tin bromide ethoxide.

Optically active dinuclear palladium complexes containing a Pd-Pd bond were prepared by using (R,R)-bis(tert-butylmethylphosphino)methane ((R,R),t-Bu-MiniPHOS). The dinuclear palladium complexes coupled with silver triflate exhibited good to excellent enantioselectivities up to 99% in palladium-catalyzed alkylative ring-opening reactions of azabenzonorbornadienes.

General synthetic methods of substituted carbocyclic aromatic compounds are reported. Ring-closing enyne metathesis (RCEM)/dehydration of 1,5-octadien-7-yn-4-ols 6 and RCEM/tautomerization of 1,5-octadien-7-yn-4-ones 7 furnished a wide variety of substituted styrenes 4 and 4-vinylphenols 8, respectively. Acyclic precursors 6 and 7 were readily prepared from beta-halo-alpha,beta-unsaturated aldehydes 9 or 3-halo-2-propene-1-ols 13 by utilizing combinations of the Sonogashira coupling, allylation, and the Dess-Martin oxidation. The RCEM/dehydration for the synthesis of 1,3,5-tris(1-phenylethenyl)benzene derivative 4r and the RCEM/RCM/dehydration for the synthesis of 1,1&apos;-binaphthyl derivative 19a are also presented as applications of this method.

Nitrosoaldol reaction between alkenyl trichloroacetates and nitrosobenzene has been achieved using dibutyltin dimethoxide as a catalyst, which is regenerated in the presence of methanol. The corresponding α-hydroxyamino ketones (N-adducts) have exclusively formed not only from cyclic alkenyl trichloroacetates but also from acyclic ones. © Georg Thieme Verlag Stuttgart.

New synthetic routes to substituted 3-hydroxypyridines 6 are presented. Ring-closing olefin metathesis (RCM)/elimination and RCM/oxidation/deprotection of nitrogen-containing dienes 4 are the key processes of the routes. An application of RCM/oxidation/deprotection to the synthesis of 3-aminopyridine 13f is also described.

A screening method for asymmetric catalysts is reported in which a metal-containing optically-active product of an asymmetric reaction is employed as a chiral catalyst in another asymmetric reaction; the rapid preparation and instant testing system of catalysts resulted in a considerable reduction in the time required for the screening process.

Nitrogen-tethered bisimidazoline (Nb-imidazoline) ligand was utilized in the Cu(I)-catalyzed benzoylation of 1,2-diols. With the assistance of i-Pr(2)NEt, the reaction of rac-1,2-diols with o-methylbenzoyl chloride was smoothly catalyzed by Nb-imidazoline-CuCl in CH(2)Cl(2) to give the corresponding o-methylbenzoylated secondary alcohols in tip to 79% ee.

The Michael addition of alkenyl trichloroacetates to p-ben-zoquinone was achieved using dibutyltin dimethoxide as a catalyst in a mixed solvent consisting of THF and MeOH. Various monoalkylated benzoquinone derivatives were obtained from cyclic and acyclic trichloroacetates in moderate yield, trans-β-Nitrostyrene was also a favorable electrophile in this catalytic process, which gave an expected Michael adduct. Copyright © 2008 The Chemical Society of Japan.