柳澤 章

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.

A catalytic asymmetric Henry reaction has been developed with use of a sulfonyldiamine-CuCl complex as a catalyst. A series of new binaphthyl-containing sulfonyldiamine ligands (2a-h) were readily synthesized in two steps starting from commercially available chiral 1,2-diamines. The (R,R)-diamine-(R)-binaphthyl ligand (2d)-CuCl complex smoothly catalyzed the enantioselective Henry reaction with the assistance of pyridine to give the corresponding adduct with high enantiomeric excess (up to 93%). Moreover, the 2d-CuCl-pyridine system promotes the diastereoselective Henry reaction in syn-selective manner to give the adduct in up to 99% yield with 92:8 syn/anti selectivity. The enantiomeric excess of the syn-adduct was 84% ee.

Since the first report of silver(i)-catalyzed asymmetric aldol-type reaction of activated isocyanides with aldehydes using a chiral ferrocenylphosphine as a chiral phosphine ligand has been appeared in 1990, various chiral phosphine-silver(i) catalysts have been utilized in asymmetric transformations. This feature articles describes recent examples of chiral phosphine-silver(i) complex-catalyzed asymmetric reactions such as allylation, aldol reaction, Mannich-type reaction, hetero-Diels-Alder reaction, 1,3-dipolar cycloaddition and nitroso aldol reaction. © The Royal Society of Chemistry.

A new strategy for the encapsulation of magnetic nanobeads was developed by using the in situ self-assembly of an organic-inorganic hybrid polymer. The hybrid polymer of {[Cu(bpy)(BF(4))(2)(H(2)O)(2)](bpy)}(n) (bpy=4,4'-bipyridine) was constructed on the surface of amino-functionalized magnetic beads and the resulting hybrid-polymer-encapsulated beads were utilized as catalysts for the oxidation of silyl enolates to provide the corresponding a-hydroxy carbonyl compounds in high yield. After the completion of the reaction, the catalyst was readily recovered by magnetic separation and the recovered catalyst could be reused several times. Because the current method did not require complicated procedures for incorporating the catalyst onto the magnetic beads, the preparation and the application of various other types of organic-inorganic hybrid-polymer-coated magnetic beads could be possible.

A library of imidazoline-aminophenol ligands was synthesized on solid supports. After immobilization of chiral chloromethylimidazolines 1 and 2 onto the polystyrylsulfonyl chloride, nucleophilic substitution with (R)or (S)-phenylethylamine (3 and 4) provided four combinations of polymer-supported imidazoline-amine ligands. Further reductive alkylation using salicylaldehydes 7-10 provided a series of imidazoline-aminophenol ligands (L9-L24). Analysis by solid-phase catalysis/circular dichroism high-throughput screening of a copper-catalyzed Henry reaction revealed that ligand L25, comprising a (S,S)-diphenylethylenediamine-derived imidazoline, (S)-phenyle-thylamine, and dibromophenol, was highly efficient, thus providing the adduct of nitromethane and benzaldehyde in 95% ee. The combination of stereogenic centers was crucial in promoting the highly stereoselective reactions. The unique reaction sphere of L25 was also examined in a FriedelCrafts alkylation of indole and nitroalkene to give the adduct in up to 83% ee.

A Barbier-type regioselective propargylation of aldehydes and ketones with (3-bromobut-1-ynyl)trimethylsilane has been achieved using reactive barium as a low-valent metal in THF. Especially in the case of ketones, the corresponding homopropargylic alcohols form almost exclusively. In the reaction of α,β-unsaturated carbonyl compounds, only 1,2-adducts have been observed. This method is also applicable to propargylation of imines, and the corresponding homopropargylic amines are obtained regiospecifically in good yields with diastereomeric ratios of up to 87:13. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

A tandem cross-coupling reaction of aryl methyl ketones with aromatic aldehydes has been accomplished employing barium isopropoxide as a catalyst, in which barium enolates are generated and then three consecutive reactions (aldol reaction/β-elimination/conjugate addition) occur; this one-pot procedure is a convenient method to obtain symmetrical 1,5-diketones in good yields. In some cases, addition of iso-propanol is effective in improving the chemical yield. © 2007 Elsevier Ltd. All rights reserved.

The chiral diamine ligand 3 was designed and synthesized from (R,R)-1,2-diphenylethylenediamine, (S)-2,2'-dibromomethyl-1,1'-binaphthalene, and o-xylylene dibromide. The resulting 3-Cu(OAc)(2) complex was a highly efficient catalyst for the Henry reaction, giving the various nitroaldols with over 90% ee (up to > 99%). The reaction was performed in n-propyl alcohol at room temperature, and the Henry adducts were produced in high yield with excellent enantiomeric excess; these attributes are desirable in a catalyst for practical use.

Catalytic asymmetric benzoylation of 1,2-diols has been developed using a solid-phase asymmetric catalyst. The reaction conditions were optimized by the screening of different metal salts, solvents, bases, and temperatures. High-throughput screening was performed using circular dichroism detection, and the results revealed that Nb-imidazoline-copper(I) in combination with diisopropylethylamine was able to catalyze with high enantioselectivity, giving the monobenzoylated products in high yields and excellent enantiomeric excesses of up to 95% ee.

A family of chiral salicylhydrazones was designed and synthesized for application in asymmetric catalysis. The ability of newly prepared binaphthyl-containing salicylhydrazones as the chiral ligand was examined in the addition of diethylzinc to aldehyde, with the desired product obtained in up to 80% ee. (c) 2007 Elsevier Ltd. All rights reserved.

A catalytic asymmetric aldol reaction of alkenyl trichloroacetates with aldehydes was achieved using dibutyltin dimethoxide and BINAP · silver(I) complex as catalysts in a mixed solvent consisting of THF and MeOH. Various optically active β-hydroxy ketones were diastereoselectively obtained not only from aromatic and α,β-unsaturated aldehydes but also from an aliphatic aldehyde with good enantioselectivity up to 92% ee. © 2006 Elsevier B.V. All rights reserved.

Barium hydride promoted regioselective dimerization and cross-coupling reactions of 2-cycloalken-1-ones were achieved in the presence of HMPA or DMPU as a Lewis base. The cross-coupling reaction between 2-cyclopenten-1-one and chalcone derivatives followed by intramolecular cyclization provides bicyclic 1,5-diketones, which have a norbornane skeleton, regio- and stereospecifically in moderate to high yields.

Direct α-hydroxylation of ketones using molecular oxygen was accomplished by organic-inorganic hybrid polymers. A newly prepared Cu-piperazine hybrid polymer was tolerant to the basic conditions, and with employment of lithium hydroxide smoothly catalyzed the α-hydroxylation of ketones. In the present catalytic process not only tetralone derivatives, but also acyclic ketones were converted to the α-hydroxy ketones in good yield. Copyright © 2006 The Chemical Society of Japan.

A tandem cross-coupling reaction of ketones with aldehydes has been achieved using barium hydride or isopropoxide as a promoter, in which barium enolates are generated in situ and then three successive reactions (aldol reaction-β-elimination-Michael addition) follow; this one-pot process is effective for obtaining symmetrical 1,5-diketones in good yields. © Georg Thieme Verlag Stuttgart.

A catalytic allyl-transfer reaction from tertiary homoallylic alcohols to aldehydes was achieved using dibutyltin oxide as a catalyst in toluene under reflux conditions. Various secondary homoallylic alcohols were prepared in high yield (up to 99%). When beta-alkylated tertiary homoallylic alcohols were used, branched products were exclusively obtained.

Asymmetric protonation of lithium enolates was examined using commercially available amino acid derivatives as chiral proton sources. Among the amino acid derivatives tested, Nβ-L-aspartyl-L-phenylalanine methyl ester was found to cause significant asymmetric induction in the protonation of lithium enolates. The enantiomeric excess (up to 88% ee) of the products obtained in the presence of a catalytic amount of the chiral proton source was higher than those obtained in the stoichiometric reaction. © 2006 American Chemical Society.

Pulse saturation transfer (PST)/MAS was highly effective for enhancing a magic angle spinning (MAS) C-13 NMR of the inter-mobile region of polymer supported organic compounds. Direct monitoring of solid-phase synthesis on non-destructed Syn-Phase lantern was demonstrated using a 7 mm probe on the C-13 PST/MAS NMR study. (c) 2006 Elsevier Ltd. All rights reserved.

A catalytic asymmetric protonation of trimethylsilyl enolates was achieved using a 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP)-silver(I) fluoride complex as a chiral catalyst in a mixed solvent consisting of dichloromethane and methanol. Various nonracemic ketones possessing a tertiary asymmetric carbon at the α-position were prepared with high enantioselectivity up to 99% ee. © 2006 IUPAC.

The direct approach: A new high-throughput screening system for analyzing the asymmetric induction in catalytic enantioselective synthesis couples solid-phase reactions with a circular dichroism detection system (see picture). Thus, direct monitoring of asymmetric induction without the need for purification or chromatographic analysis is obtained. (Figure Presented). © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

Oxidation of silyl enolates was found to be smoothly catalyzed by [Cu(bpy)(BF4)2(H2O)2(bpy)] n (bpy = 4,4′-bipyridine) under molecular oxygen, and provided the corresponding α-hydroxy carbonyl compounds in high yield. The insoluble organic-inorganic hybrid polymer was readily recovered by centrifugation after the completion of reaction, and the recovered catalyst could be reused. Copyright © 2005 The Chemical Society of Japan.

A novel Mannich-type reaction of alkenyl trichloroacetates with aldimines has been realized by using dibutyltin dimethoxide as a catalyst, which is regenerated by addition of methanol. A three-component coupling reaction of aldehydes, primary amines, and alkenyl trichloroacetates has been also efficiently achieved. These procedures can provide a variety of β-amino ketones not only from aromatic aldehydes but also from α,β- unsaturated aldehydes mainly with syn-selectivity in high yields up to 99%. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

A chiral nitrogen-tethered bis (imidazoline) ligand (Nb-imidazoline) was newly designed and synthesized in a divergent strategy. Thus, a single coupling reaction of primary amine with two molecules of chloromethylated imidazoline provided the Nb-imidazoline. The copper(II) triflate complex of Nb-imidazoline catalyzed a trans-selective cyclopropanation of styrene with ethyl diazoacetate to give the adduct in high chemical yield with good enantiomeric excess up to 83%.

A Barbier-type propargylation of aldehydes with (3-bromoprop-1-ynyl) trimethylsilane has been achieved using reactive barium as a low-valent metal in THF. This process is effective also for obtaining the desired homopropargylic alcohols in high yields from the corresponding ketones including enolizable ketones such as cyclopent-2-enone. © Georg Thieme Verlag Stuttgart.

Silver lining: A catalytic enantioselective protonation of trimethylsilyl enolates uses a binap/silver(I) fluoride complex as a chiral catalyst in a mixture of dichloromethane and methanol (see scheme). Various ketones with tertiary asymmetric carbon centers at the α position can be prepared with high enantioselectivities. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

(Chemical Equation Presented) Various α,β-unsaturated ketones were stereoselectively synthesized in high yields up to 94% by a condensation reaction between alkenyl trichloroacetates and aldehydes using dibutyltin dimethoxide as a catalyst in the presence of methanol. This process is superior to the classical Claisen-Schmidt condensation with respect to mildness of the base catalyst and product selectivity.

An asymmetric allylation of aldehydes with tetraallyltin and other allylstannanes was achieved using L-aspartic acid as a chiral promoter in DMF. Various optically active homoallylic alcohols were obtained in high yields with moderate enantioselectivities up to 40% ee. © 2004 Elsevier Ltd. All rights reserved.

A Reformatsky-type aldol reaction of α-chloroketones with aldehydes has been achieved using reactive barium as a low-valent metal in THF; this one-pot process is more effective for obtaining the desired β-hydroxy ketones in high yields than the stepwise process in which barium enolates are prepared prior to the reaction with aldehydes. © 2004 The Royal Society of Chemistry.

A catalytic aldol condensation of aldehydes with enol trichloroacetates was achieved using dibutyltin dimethoxide as a novel catalyst in a mixed solvent consisting of THF and MeOH. Various beta-hydroxy ketones were diastercoselectively obtained in high yields up to 99%. (C) 2003 Elsevier Ltd. All rights reserved.

A catalytic amount of KF(.)18-crown-6 complex is effective as a soluble fluoride source to activate an asymmetric Sakurai-Hosomi allylation with BINAP and silver(l) triflate catalyst. The allylation of a variety of aromatic, alpha,beta-unsaturated and aliphatic aldehydes with allylic trimethoxysilane resulted in high yields and remarkable enantioselectivities. In addition, the asymmetric Mukaiyama-type aldol reaction is achieved by using trimethoxysilyl enol ethers in the presence of the same catalysts. High anti selectivity is obtained from E-silyl enol ether, while Z-silyl enol ether gives syn selectivity.

The reaction of lithium enolates of α-amino acid derivatives with chiral amides, easily synthesized from l-tert-leucine, gives corresponding optically active unnatural α-amino acid derivatives with up to 87% ee. © 2003 The Royal Society of Chemistry.

Enol trichloroacetate of cyclohexanone has been found to react with benzaldehyde in the presence of a catalytic amount of tributyltin methoxide and stoichiometric amount of MeOH to give an aldol adduct. Methanolysis of the in situ generating tin alkoxide of aldol adduct regenerates the tin methoxide, and thus the aldol reaction can proceed catalytically. The use of BINAP-silver(I) complex as an additional catalyst results in formation of optically active aldol products. This catalytic method has been further applied to the asymmetric reaction of diketene with benzaldehyde. (C) 2002 Elsevier Science Ltd. All rights reserved.

Catalytic asymmetric Mukaiyama-type aldol reaction using trimethoxysilyl enol ethers was achieved using 2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl (p-Tol-BINAP)·AgF complex as a catalyst. The chiral silver(I) catalyst was easily generated by mixing p-Tol-BINAP and silver(I) fluoride in MeOH at room temperature. High syn- and enantioselectivities were obtained from both the E- and Z-silyl enol ethers. Use of a 1:1 mixture of MeOH and acetone as a solvent in the reaction of cyclohexanone-derived trimethoxysilyl enol ethers resulted in higher enantioselectivity.

Catalytic asymmetric allylation of aldehydes with allylic trialkylstannanes was achieved with BINAP·AgOTf complex as catalyst. The chiral silver(I) catalyst was readily prepared by stirring an equimolar mixture of BINAP and silver(I) triflate in TI-IF at room temperature. The allylation of a variety of aromatic and α,β-unsaturated aldehydes resulted in high yields and remarkable enantioselectivities. Addition of γ-substituted allylstannanes such as 2-butenyltributyl-stannane and trialkyl-2,4-pentadienylstannanes exclusively gave γ-adducts. High anti-selectivity was also obtained in the reaction with 2-butenyltributylstannane, irrespective of the configuration at the double bond.

New catalytic asymmetric Mukaiyama-type aldol reaction using trimethoxysilyl enol ethers was achieved using p-Tol-BINAP·AgF complex as a catalyst. High syn- and enantioselectivities were obtained both from the E- and Z-silyl enol ethers.

Chiral alcohols possessing an asymmetric 2-oxazoline ring were synthesized as new chiral Brønsted acids from tetrahydro-2-furoic acid and (1S, 2R)-2-amino-1,2-diphenylethanol. These alcohols were superior to (S,S)- or (R,R)-imide reported previously as a chiral proton source for enantioselective protonation of lithium enolate of an alanine derivative.

The catalytic enantioselective protonation of simple enolates was achieved using a catalytic amount of chiral imides and stoichiometric amount of achiral proton sources. Among the achiral proton sources examined in the protonation of the lithium enolate of 2,2,6-trimethylcyclohexanone catalyzed by (S,S)-imide 1, 2,6-di-tert-butyl-p-cresol (BHT) and its derivatives gave the highest enantiomeric excess. For example, 90% ee of (R)-enriched ketone was obtained when (S,S)-imide 1 (0.1 equiv) and BHT (1 equiv) were used. Use of 0.01 equiv of the chiral catalyst still caused a high level of asymmetric induction. For catalytic protonation of the lithium enolate of 2-methylcyclohexanone, chiral imide 6 possessing a chiral amide portion was superior to (S,S)-imide 1 as a chiral proton source and the enolate was effectively protonated with up to 82% ee.

(S,S)-Ethylenebis (tetrahydroindenyl) titanium chloride methoxide, (S,S)-(EBTHI)TiCl(OMe) (3) was synthesized from the corresponding titanium dichloride. The asymmetric aldol reaction of enol trichloroacetate of cyclohexanone 1 with aromatic aldehydes was studied in the presence of a catalytic amount of the chiral titanium complex 3, with the result that the optically active syn aldol adduct 2 was preferentially obtained with up to 91% ee. (C) 2000 Wiley-Liss, Inc.

New chiral imides possessing a chiral amide can be prepared from 1,3,5- trimethyl-r-1,c-3,c-5-cyclohexanetricarboxylic acid or related triacids and optically active amines. These imides are superior to 1,3,5-trimethyl-c- 5[(4S,5S)-4,5-diphenyl-2-oxazolin-2-yl]-r-1,c-3-cyclohexanedicarboximide reported previously as a chiral proton source for enantioselective protonation of lithium enolates of 2-alkylcycloalkanones.

Catalytic asymmetric allylation of aldehydes with allylic trimethoxysilanes was achieved with the p-Tol-BINAP-AgF complex as catalyst [Eq.(a); p-TolBINAP = 2,2'-bis(di-p-tolylphosphanyl)-1,1'-binaphthyl)]. High anti and enantioselectivities were obtained in the reaction with crotyltrimethoxysilane, irrespective of the configuration at the double bond.

Reaction of lithium enolates of 2-arylcycloalkanones 2 with (R,R)-aminoborane 1, prepared from (1R,2R)-1,2-diaminocyclohexane 4 and PhBCl2, gives the corresponding optically active ketones 3 with up to 93% ee; this is the first example of enantioselective protonation using a metal-containing chiral proton source.

New chiral proton sources possessing an asymmetric 2-oxazoline ring, (S,S)-imide 1 and related imides, were synthesized from Kemp's triacid and optically active 2-amino alcohols. With these chiral imides, various lithium enolates of α-monoalkylated cycloalkanones were effectively protonated with excellent to moderate enantioselectivity. An increase in enantioselectivity was observed in the asymmetric protonation of prochiral enolates with (S,S)- imide 1 using lithium salt as an additive. For example, (R)-enriched 2-n- pentylcyclopentanone 35 was obtained in high yield with 90% ee when the silyl enol ether 33 was treated with n-BuLi in the presence of 5 equiv of LiBr in Et2O, and the resulting lithium enolate 34 was then protonated by a solution of (S,S)-imide 1 in THF. In contrast, the product 35 obtained without LiBr exhibited a lower enantiomeric excess (74% ee).

The diastereoselective aldol reaction of tributyltin enolale of cyclohexanone with benzaldehyde was studied in the presence of a catalytic amount of various metal triflates. The highest anti selectivity was observed with Pd(OTf)2, while Zn(OTf)2 in THF showed moderate syn selectivity. The use of (S,S)-iPr-pybox 3-Cu(OTf)2 complex as a catalyst preferentially produced the optically active syn aldol adduct with 84% ee.

A variety of Lewis acid reagents were utilized for Diels-Alder, aldol, and ene reactions with high enantioselectivities. The origin of the selectivity of these reactions is discussed.

An increase in enantioselectivity was observed in the asymmetric protonation of prochiral enolates with a chiral imide using lithium salt as an additive. For example, (R)-enriched 2-n-pentylcyclopentanone 6 was obtained in high yield with 90% ee when the silyl enol ether 4 was treated with n-BuLi in the presence of 5 equiv of LiBr in Et2O and the resulting lithium enolate 5 was then protonated by a solution of (S,S)-imide 1 in THF. In contrast, the product 6 obtained without LiBr exhibited a lower enantiomeric excess (74% ee).

Reaction of aldehydes with methallyltributyltin or crotyltributyltin in the presence of a catalytic amount of BINAP·silver(I) complex affords the corresponding optically active homoallylic alcohols with high enantioselectivities; γ- and antiselectivities are also obtained for crotyltributyltin.

Described herein are two methods of asymmetric protonation of enol derivatives under acidic and basic conditions. The process under basic conditions is protonation of prochiral simple enolates with (S,S)-imide 1 which possesses an asymmetric 2-oxazoline ring. Various lithium enolates derived from the corresponding alpha-monoalkylated cycloalkanones have been protonated by 1 and (R,R)imide 2 with 97-68% ee. The catalytic enantioselective protonation of lithium enolate has been realized using a catalytic amount of (S,S)-imide 1 and stoichiometric amount of an achiral proton source. Diastereoselective protonation of lithium enolate of (-)-menthone has also been achieved stoichiometrically and catalytically. The process under acidic conditions is protonation of silyl enol ethers and ketene bis(trialkylsilyl) acetals with Lewis acid assisted chiral Bronsted acid (LBA) which is prepared from optically active binaphthol and tin tetrachloride. The catalytic process has been realized using a catalytic amount of optically active 2-hydroxy-2'-methoxy-1,1'-binaphthyl and a stoichiometric amount of 2,6-dimethylphenol in the presence of tin tetrachloride.

An increase of α-regioselectivity was observed in the reaction of allylic barium reagents with aldehydes employing crown ether as an additive. For example, an α/γ regioselectivity was improved to 98/2 from 92/8, when an equimolar amount of 18-crown-6 was added to geranylbarium reagent in THF at -78°C prior to the reaction with benzaldehyde.

Reaction of aldehydes with (E)-2,4-pentadienyltributyltin or trimethyltin in the presence of a catalytic amount of BINAP-silver(I) complex affords the corresponding γ-pentadienylated optically active alcohols with high enantioselectivities.