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Significance X-ray crystallographic analyses of mitochondrial cytochrome c oxidase (CcO) have been based on its dimeric form. Recent cryo-electron microscopy structures revealed that CcO exists in its monomeric form in the respiratory supercomplex. This study, using amphipol-stabilized CcO, shows that the activity of monomer is higher than that of the dimer. The crystal structure of monomer determined here shows that the local structure of one of the proton transfer pathways differs from that in the dimer. The crystal structure also shows that cardiolipins are located at the interface region in the supercomplex. Taken together, these results suggest that CcO in the monomeric state, dimeric state, and supercomplex state depending on cardiolipins are involved in regulation of respiratory electron transport., Cytochrome c oxidase (CcO), a membrane enzyme in the respiratory chain, catalyzes oxygen reduction by coupling electron and proton transfer through the enzyme with a proton pump across the membrane. In all crystals reported to date, bovine CcO exists as a dimer with the same intermonomer contacts, whereas CcOs and related enzymes from prokaryotes exist as monomers. Recent structural analyses of the mitochondrial respiratory supercomplex revealed that CcO monomer associates with complex I and complex III, indicating that the monomeric state is functionally important. In this study, we prepared monomeric and dimeric bovine CcO, stabilized using amphipol, and showed that the monomer had high activity. In addition, using a newly synthesized detergent, we determined the oxidized and reduced structures of monomer with resolutions of 1.85 and 1.95 Å, respectively. Structural comparison of the monomer and dimer revealed that a hydrogen bond network of water molecules is formed at the entry surface of the proton transfer pathway, termed the K-pathway, in monomeric CcO, whereas this network is altered in dimeric CcO. Based on these results, we propose that the monomer is the activated form, whereas the dimer can be regarded as a physiological standby form in the mitochondrial membrane. We also determined phospholipid structures based on electron density together with the anomalous scattering effect of phosphorus atoms. Two cardiolipins are found at the interface region of the supercomplex. We discuss formation of the monomeric CcO, dimeric CcO, and supercomplex, as well as their role in regulation of CcO activity.

To ensure high enantiopurity of the product, enantio-differentiating hydrogenation of methyl acetoacetate over a (R,R)-tartaric acid-modified Raney nickel catalyst is normally performed under eleva...

Chiral (R,R)-tartaric acid and NaBr-doubly modified Raney nickel (TA-MRNi) is a promising heterogeneous catalyst for enantioselective hydrogenation of prochiral β-keto esters. To obtain deeper insi...

A unique electron-accepting analog of vitamin K1 found in photosystem I in several species of oxygenic photosynthetic microorganisms was confirmed to be 5′-hydroxyphylloquinone (1) through stereo-uncontrolled synthesis. Furthermore, the stereochemistry of 1 obtained from Synechococcus sp. PCC 7942 was assigned to be 5′S using proline-catalyzed stereocontrolled reactions.

The effects of the pretreatment and Pd-distribution on the enantioselective hydrogenation of α-phenylcinnamic acid over cinchonidine-modified Pd/C and Pd/Al2O3 were studied by use of EXAFS techniques combined with thiol adsorption. It is suggested that the enhanced performance by the H2-pretreatment at 353 K is ascribed to the elimination of contaminants and/or H2O from Pd/C. The Pd–S CN is related to the Pd dispersion and the reactivity and diffusivity of thiols used.

The enantioselective hydrogenation reactions of α-phenylcinnamic acid (PCA) and 4,4′-dimethoxy α-phenylcinnamic acid (DMPCA) were carried out over chiral cinchona alkaloid-modified Pd/C. Two sets of the modifiers were employed to get deeper insights into the effects of relative adsorption strength between the modifier and the substrate on the enantioselectivity; cinchonidine (CD)/cinchonine (CN) and quinine (QN)/quinidine (QD). The performances of the two sets of modifiers were compared by systematically varying the modifier concentration over a wide range. It was clearly substantiated that the origin of the low selectivity observed with QN/QD at an ordinary concentration is primarily due to its weak adsorption strength on Pd metal surface, which originates from the steric hindrance of the methoxy substituent at C6. A new modifier, 6-hydroxy CD, was found to exhibit a performance comparable to that of CD, implying that the steric hindrance of the 6-methoxy group of QN/QD is much more influential than the ...

A successful asymmetric total synthesis of (–)-azaspirene has been accomplished by utilizing (3R)-6-cinnamyl-3-methyl-3-phenyl-1,4-dioxane-2,5-dione, a readily accessible chiral template. The present method involves two distinctive TiCl4/amine-mediated reactions: (i) an asymmetric Ti-crossed-Claisen condensation of the chiral template with propanoyl chloride followed by methanolysis to afford methyl (2R)-(4E)-2-hydroxy-5-phenyl-2-propanoylpent-4-enoate, the key chiral synthon and (ii) a robust Ti-direct aldol addition reaction, instead of the reported lithium diisopropylamide/hexamethylphosphorictriamide (LDA/HMPA) or potassium hexamethyldisilazide (KHMDS)-mediated reaction, by using the trimethylsilyl (TMS) ether of α-acyl-γ-lactam to successfully furnish the new aldol adduct. Final oxidation, cyclization, and tert-butyldimethylsilyl (TBS) removal produced (–)-azaspirene from the key template in 23 steps (total yield 1.7 %).

The enantioselective hydrogenation of the aromatic β-ketoesters, methyl 3-phenyl-3-oxypropanoate ( 1 ) and its p -methoxy-analogue ( 2 ), was studied over tartaric acid-modified Raney nickel catalysts. A competitive hydrogenation approach was used to clarify the catalytic behaviors of the enantio-differentiating hydrogenation of aromatic β-ketoesters over tartaric acid-modified Raney nickel, malic acid-modified Raney nickel, and unmodified Raney nickel in comparison with aliphatic one, represented by methyl acetoacetate. We found that the enantioselectivity could be elucidated by the interaction modes between the surface modifier, Ni metal surface, and the substrate as well as the keto/enol ratio of the substrate. We suggest that the moderate enantioselectivity of 1 over tartaric acid-modified Raney nickel is the result of distorted, weak two-point hydrogen bond interactions with surface tartrate due to unfavorable phenyl–Ni metal surface interactions. The p -methoxy group of 2 suppresses the phenyl–Ni metal surface interactions, resulting in an increase in the enantioselectivity of 2 over tartaric acid-modified Raney nickel. Ligand acceleration effects were observed with methyl acetoacetate and 2 but not with 1 .

A highly regiocontrolled acid-induced Favorskii-type elimination reaction using unsymmetrically-substituted acyloin mesylates proceeded smoothly to give more substituted α,β-unsaturated ketones under mild conditions. Not only acyclic mesylates but also cyclic acyloin mesylates produced the corresponding higher substituted (thermodynamically stable) α,β-unsaturated ketones via distinctive double-bond-migration pathway. The regioselectivity is nearly exclusive in all 8 examples examined. A plausible fundamental pathway for this regiocontrolled elimination is proposed; (1) isomeric enol and/or cyclopropane formations proceeds to give the cationic intermediate and/or the cyclopropane intermediate, respectively, (2) successive crucial step for regioselective MsOH (or H2O) elimination concomitant with specific proton withdrawal leads to the corresponding intermediates, the major E1’-like dienol and the minor E1-like dienol, (3) final tautomerization affords more substituted α,β-unsaturated ketones. Mechanistic speculations for the plausible mechanism and exo/endo selectivity for cyclic acyloin mesylates are also described. The present reaction was applied to a successful synthesis of “chiral” (R)-muscone precursor from readily available “racemic” muscone.

Enantioselective hydrogenation of α-phenylcinnamic acid (PCA) and p,p′-dimethoxyphenylcinnamic acid (DMPCA) was studied over a variety of commercial 5 % Pd/C catalysts to reveal catalyst properties suitable for obtaining high enantioselectivity. The catalysts were characterized by CO adsorption, X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). It is confirmed that pretreatment at 353 K under atmospheric pressure of H2 before modification with cinchonidine is very effective for all the Pd/C catalysts used here to improve the selectivity and reaction rate. It is suggested that the distribution of Pd metal particles is crucial to attain high selectivity (ee% = 79 ± 1 for PCA, 89 ± 2 for DMPCA): a uniform or eggshell-type distribution of Pd is more suitable than an egg-white or egg-yolk-type distribution. It is also suggested that the dispersion of Pd metal particles controls the enantioselectivity over cinchonidine (CD)-modified Pd/C catalysts. XPS techniques are proposed to provide a convenient method to find desirable catalysts. The choice of such Pd/C catalysts could facilitate high-throughput guided study on highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids.

The chiral guanidine-catalyzed conjugate addition of 5H-oxazol-4-ones to 2-chloroacrylonitrile was developed with high enantiomeric and diastereomeric control. Introduction of an electron-donating 4-methoxyphenyl group as an aromatic substituent (Ar) on 5H-oxazol-4-one was suitable for inhibiting undesirable cyclization and achieving high stereoselectivity in this conjugate addition. The derivatization of an obtained product was also performed to afford a chiral α-siloxyimide, which was subsequently converted to the corresponding α-siloxy-γ-lactam in a few steps.

The hydrogenation of substituted 2,3-diarylpropenoic acids over cinchonidine-modified Pd/C showed obvious ligand acceleration effects with the substrates yielding over 90% enantiomeric excess (ee). 2,3-Di(methoxyphenyl)propenoic acid exhibited profound ligand acceleration, and its hydrogenation rate relative to the rate on unmodified Pd/C was 370%, yielding 91%ee. 3-(p-Fluorophenyl)-2-(o-methoxyphenyl)propenoic acid showed 92%ee with an activity increase of 230%. It is considered that the difference is caused by the ortho-methoxy substituent on the α-phenyl ring. The substituent effect of the ortho-substituent on the α-phenyl ring demands the presence of an electron-donor substituent on the β-phenyl ring. A remarkable substituent effect was observed with 3-(p-methoxyphenyl)-2-(o-methoxyphenyl)propenoic acid, which attained up to 93%ee. The factors affecting enantioselectivity results are analyzed for each substituent.

In this Letter, a chiral guanidine-catalyzed 1,4-addition reaction of 5H-oxazol-4-ones to vinyl ketones is described. The 1,4-addition reaction proceeded with a high enantioselectivity using 5H-oxazol-4-ones, substituted with a 3-chloro-5-methylphenyl group, as pronucleophiles and a newly developed chiral guanidine as a catalyst. The optimized reaction conditions were also effective in achieving excellent enantioselectivity in the 1,6-addition to dienones. Subsequent solvolysis of the 1,4-addition adduct yielded the corresponding α-hydroxy-5-oxocarboxylates.

A unique electron-accepting analog of vitamin K

The enantioselective hydrogenation of α-phenylcinnamic acid (PCA) was performed using a cinchonidine (CD)-modified Pd/C catalyst, and the conversion and enantiomeric excess (ee) of the product were monitored during the reaction. Low ee values were observed only during the initial stages of the reaction (

Asymmetric hydrogenation of α-phenylcinnamic acid catalyzed by cinchonidine (CD)-modified palladium has been performed. Without benzylamine (BA), a modification inconsistency was observed: the rate...

Optically active (2 S ,4 R )-2-hydroxy-4-pentyl enol ether was prepared for the first time and subjected to hydroxy-directed oxidations at the olefinic group. Treatment with m -chloroperbenzoic acid and tert -butyl hydroperoxide/vanadium acetylacetonate resulted in the same stereoface differentiation at the olefin, with diastereomeric excesses as high as 79% and 92%, respectively, whereas the stereochemistry of the products of subsequent nucleophilic additions of the hydroxy group was opposite.

The hydrogenation of 5-alkylidene-2,4-thiazolidiones was studied using Pd/C to establish an alternative process for pioglitazone synthesis. The reportedly sluggish reactivity was due to the high reaction temperature in formic acid. The conditions were improved to 1 atm at 296 K, which results in a quantitative product with a smaller amount of the catalyst.

4-(Diphenylphosphino)benzoic acid was used for the Mitsunobu reaction as a bifunctional reagent that served as both a reductant and a pronucleophile. When combined with di-2-meth­oxyethyl azodicarboxylate, inversion of a secondary alcohol stereospecifically occurred to give an ester carrying a phosphine oxide group. The reaction mixture was directly hydrolyzed to give an inverted secondary alcohol in sufficient stereo and chemical purities by the presently developed chromatography-free process in conjunction with basic extraction, drying, and concentration.

An appropriate solvent to perform the original Simmons–Smith reaction was reinvestigated. Among available solvents, cyclopentyl methyl ether (CPME), a recently commercialized ethereal solvent, was found to be the best so far. Compared with Et2O under reflux – the commonest conditions – reaction completion in CPME at 50 °C was about 10 times faster. The product yields and selectivities were mostly identical to those with Et2O, but were better in some cases; e.g. 13–56% with 2-cyclohexenol. The good performance of CPME should be mainly due to its moderate polarity and high boiling point. Copyright © 2012 John Wiley & Sons, Ltd.

2-Formyl(thio)esters were utilized as pronucleophiles to obtain less-accessible acyclic chiral building blocks bearing versatile functional groups on a quaternary carbon atom for enantioselective 1,4-addition to vinylketones. To achieve high enantioselectivity in the present 1,4-addition reaction, thiourea-tertiary amines containing a bulky chiral backbone were developed as catalysts, and several derivatizations of the products were performed to demonstrate the synthetic utility of the products.

Enantioselective hydrogenation of α-phenylcinnamic acid was investigated on Pd/C catalysts prepared in our laboratory to compare activity and selectivity with those on commercial Pd/C and Pd/TiO 2 catalysts. The Pd/C catalysts after the 353 K-H 2 -pretreatment exhibited satisfactory and comparable performances obtained with commercially available best ever Pd/C by optimizing catalyst preparation. In contrast to Pd/TiO 2 , a high loading of Pd is not necessary with Pd/C, but only 5% loading on a certain activated carbon was found to result in high e.e. It is suggested that the optimum size or size-distribution of Pd metal particle are different between the two supports, suggesting a support effect of this catalyst system.

A chiral guanidine-catalyzed 1,6-addition reaction of 5H-oxazol-4-ones to α,β,γ,δ-diunsaturated ketones is described in this study. The addition reaction proceeded regiospecifically to yield a 1,6-...

Cyclopropanation was performed using the Furukawa procedure with CH2I2/Et2Zn and α,β-unsaturated ketones. The reaction was performed in the presence of a copper salt. The reactivity was highly depe...

A 1,4-addition reaction of 5H-oxazol-4-ones to alkylidene β-ketoesters, which was catalyzed by using chiral guanidines via a dynamic kinetic resolution process that involved geometric isomerization of the alkylidene β-ketoesters, was developed. This method allowed using E,Z isomeric mixture of various acyclic alkylidene β-ketoesters to obtain the products stereoselectively. The relation between the geometry and the stereoselectivity of products was investigated, and the derivatization of the products to the corresponding α-acyl-γ-lactone was performed.

Two regioisomeric α-phenyl-β-pyridylacrylic acids were hydrogenated with cinchonidine (CD)-modified Pd/C. The low ee obtained was attributed to the strong adsorption of the substrate, which caused desorption of CD from the catalyst surface. The ee was improved at the low substrate/CD ratio up to 82% for the 4-pyridyl isomer. The unmodified site in the CD-modified Pd catalyst was experimentally proved to be variable depending on the relative adsorption strength between the substrate and CD. At the low substrate/CD ratio, the ee with the 3-pyridyl isomer was also improved, but the highest ee was only 45%. The difference between the isomers suggests that the strong adsorption of the substrate on the metal surface may interrupt the interaction between CD and the substrate.

Di-2-methoxyethyl azodicarboxylate (DMEAD) is prepared in 65% yield in two steps as a crystalline solid. Use of DMEAD in the Mitsunobu reaction of a variety of alcohols with pronucleophiles results in good yields of the products under sufficient stereospecificity of inversion, as conventional diisopropyl azodicarboxylate (DIAD) does. Isolation of the product is, however, much easier with DMEAD than that with DIAD, because the hydrazine produced from DMEAD is highly hydrophilic and is completely separable by a simple extraction into neutral water. Purification of the organic layer, after separation of the other by-product, triphenylphosphane oxide, by filtration, easily provides high purity of the product in a good yield. Concentration of the water layer yields the hydrazine, which can be reused for the preparation of DMEAD. One-step removal of the two by-products by the aqueous extraction was also possible when trimethylphosphane and DMEAD were employed.

Relationship between substrate structure and enantioselectivity is studied for the asymmetric hydrogenation of 42 different (E)- α , β -disubstituted acrylic acids (propenoic acids) over cinchonidine-modified Pd/C. The β-phenyl group is indispensable for high enantioselectivity of α-phenylcinnamic acid (2,3-diphenylpropenoic acid, 81% ee), and substitution on this group affects markedly the selectivity. The high ee up to 92% was achieved by the β - p -alkoxyphenyl substitution, and the selectivity is ascribed mainly to stronger interaction of the substrate with the chiral modifier on the catalyst surface. In contrast, substitution on the α-phenyl group does not affect notably the enantioselectivity (80–82% ee) or even the α-phenyl group itself is not indispensable but replaceable with a properly bulky group for the high enantioselectivity.

A robust method for preparing (3S)-3-alkyl-3-phenyl-1,4-dioxane-2,5-diones was developed using an improved cyclocondensation reaction between (S)-α-alkylmandelic acids and 2-bromocarbonyl halides. Subtle differences in the reaction conditions, including separate additions of triethylamine, significantly increased the yield compared with Schollkopf's original method.

We have developed a general, robust, and cost-effective method for the (E)- or (Z)-stereocomplementary enol tosylation of beta-ketoesters using TsCl- N-methylimidazole (NMI)-Et3N or LiOH. TsCl coupled with NMI formed a highly reactive N-sulfonylammonium intermediate. Stereocongested secondary alcohols were smoothly sulfonylated using Ts(Ms)Cl-NMI-Et3N. beta-Ketoesters underwent (E)-selective tosylation using TsCl-NMI-Et3N and (Z)-selective tosylation using TsCl-NMI-LiOH (total of 23 examples; 60%-99% yield). Stereoretentive Negishi and Sonogashira couplings using enol tosylates proceeded successfully to give trisubstituted alpha,beta-unsaturated esters.

We developed two efficient practical methods for esterification, amide formation, and thioesterification between acid chlorides and alcohols, amines, thiols, respectively. The present mild and robust reaction was performed by two separate methods both by combining cheap and readily available amines, N -methylimidazole, and N , N , N ′, N ′-tetramethylethylenediamine (TMEDA). Method A uses catalytic N -methylimidazole and TMEDA with an equimolar amount of K 2 CO 3 , whereas Method B uses equimolar amounts of N -methylimidazole and TMEDA. The salient features are as follows. (i) With regard to reactivity, Method B was superior to Method A for esterification and thioesterification, whereas cost-effective Method A was superior to Method B for amide formation. (ii) Amide formation proceeded smoothly between acid chlorides and less nucleophilic and stereocongested amines such as 2,6-dichloroaniline. (iii) This protocol was applied to the successful synthesis of two agrochemicals, bromobutide and carpropamid.

We encountered a unique phenomenon of reaction velocity reversal during the silylation between mixed simple alcohols (A; AOH) and alpha- or beta-hydroxyketones (B; BOH). The present reaction system using anilinosilanes 1a [PhNH(TMS)] (TMS-A) and 1b [PhNH(TES)] (TES-A) with the catalytic TBAF (0.02 equiv) reagent showed that the order of silylation-velocity between the independent system and the mixed system was distinctively reversed [nu(A)nu(B) approximately nu(B(mix))nu(A(mix))]. A total of seven examples indicate its high generality: AOH = linalool, 3-octanol; BOH = valeroin, benzoin, 5-hydroxy-4-methyl-3-undecanone. Time-dependent IR spectroscopy analysis rationally supported this speculation.

A pentafluorophenylammonium triflate (PFPAT) catalyst (5 mol %) successfully promoted C-acylation of enol silyl ethers with acid chloride to produce various beta-diketones (12 examples; 62-92% yield). Similarly, C-acylation of ketene silyl acetals or ketene silyl thioacetals (i.e., crossed Claisen condensation) proceeded smoothly to provide not only alpha-monoalkylated beta-keto (thio)esters but also thermodynamically unfavorable (less accessible) alpha,alpha-dialkylated beta-keto (thio)esters in good to excellent yield (38 examples; 60-92% yield).

The chiral guanidine-catalyzed conjugate addition of 5H-oxazol-4-ones to 2-chloroacrylonitrile was developed with high enantiomeric and diastereomeric control. Introduction of an electron-donating 4-methoxyphenyl group as an aromatic substituent (Ar) on 5H-oxazol-4-one was suitable for inhibiting undesirable cyclization and achieving high stereoselectivity in this conjugate addition. The derivatization of an obtained product was also performed to afford a chiral α-siloxyimide, which was subsequently converted to the corresponding α-siloxy-γ-lactam in a few steps.

The 1,6-addition of 5H-oxazolones to conjugated dienones catalyzed by chiral guanidines to yield oxazol derivatives is described.

A chiral guanidine catalyst is successfully employed for 1,4- and 1,6-addition reactions of oxazolones (I).

An efficient method for esterification between acid chlorides and alcohols in water as solvent has been developed by combining the catalytic amines, N-methylimidazole and N,N,N',N'-tetramethylethylenediamine (TMEDA). The present Schot-ten-Baumann-type reaction was performed by maintaining the pH at around 11.5 using a pH controller to prevent the decomposition of acid chlorides and/or esters and to facilitate the condensation. The choice of catalysts (0.1 equiv.) was crucial: the combined use of N-methylimidazole and TMEDA exhibited a dramatic synergistic effect. The catalytic amines have two different roles: (i) N-methylimidazole forms highly reactive ammonium intermediates with acid chlorides and (ii) TMEDA acts as an effective HCl binder. The production of these intermediates was rationally supported by a careful 1 H NMR monitoring study. Related amide formation was also achieved between acid chlorides and primary or secondary amines, including less nucleophilic or water-soluble amines such as 2-(or 4-)chloroaniline, the Weinreb N-methoxyamine, and 2,2-dimethoxyethanamine.

TiCl4-Lewis base (AcOEt, CH3NO2) complexes smoothly deprotected tert-butyldimethylsilyl (TBDMS) ethers. The reaction velocity with these complexes, which seemed less reactive due to the influence of Lewis bases, was considerably greater than that with TiCl4 alone. Selective desilylations between aliphatic and aromatic TBDMS ethers (1 and 5), between 1 and benzyl, allyl, tosyl, methoxyphenyl, and chloroacetyl ethers (13, 14, 15, 16, and 17), and between TBDMS and TBDPS ethers (18 and 19) were successfully performed. Desilylation of TBDMS-aldol, acyloin, and beta-lactam analogues 9-12 proceeded smoothly due to anchimeric assistance by the neighboring carbonyl groups. The present method was successfully applied to the practical synthesis of 1beta-methylcarbapenems 20a'-f'.

A practical method for the synthesis of optically pure α-alkylmandelic acids 1 is described. The present improved robust method involved two reactions: a mild, convenient, stereoselective preparation of chiral cis-5-aryl-2-(1-naphthyl)-1,3-dioxolan-4-ones, 9a−c, and highly diastereoselective alkylation of 9a−c, followed by the hydrolysis.

A practical synthesis of (R)-homopipecolinic acid methyl ester 1 and (R)-homoproline methyl ester 2 was performed utilizing (i) a direct intramolecular cyclization of ω-chloro-β-enamino esters 11 and 12 , which were prepared from available (S)-1-phenylethylamine or (S)-1-(1-naphthyl)ethylamine and ω-chloro-β-keto esters 5 and 10 , respectively and (ii) a highly diastereoselective NaBH4 reduction followed by hydrogenolysis. The present method is a short-step process using inexpensive and readily available substrates and reagents with fewer wasted materials.

The reagent TiCl 4 -Et 3 N was used in the Horner-Wadsworth-Emmons (HWE)-type reaction of triethylphosphonocarboxylates with aldehydes, wherein unstable intermediary aldol adducts were isolated with anti-selectivity. Subsequent Bronsted acid promoted stereoselective elimination was successfully performed using TBS-benzamide-pyridinium triflate to give the less-accessible Z-α,β-unsaturated esters.

We developed an efficient method for the silylation of alcohols using anilinosilane with tetrabutylammonium fluoride (TBAF) catalyst, wherein TMS, TES and TBS groups were smoothly introduced into silylation-resistant hindered alcohols under mild conditions.

In this paper, a chiral guanidine-catalyzed 1,4-addition reaction of 5H-oxazol-4-ones to allenic esters and ketones is described. 5H-Oxazol-4-ones substituted with a 2-chlorophenyl group were suita...

The hydrogenation of 4,4′-dimethoxy-α-phenylcinnamic acid over Pd/C showed a large ligand acceleration effect when a cinchonidine modifier was used; the hydrogen rate increased to 370% relative to ...

Esterification, sulfonylation, amide formation, and silylations are well recognized as frequently used reactions for organic syntheses. Recent syntheses of fine chemicals and complex natural products, however, require further rationalization of these reactions. We describe herein our recent studies in this area including related representative known methods.(i) Recent progresses of catalytic esterifications are surveyed and we introduce two efficient ammonium triflate catalysts (DPAT and PFPAT) for esterification between 1 : 1 mixture of carboxylic acids and alcohols. (ii) Conventional condensation reagents for esterifications, thioesterifications, and amide formation, are listed and we introduce efficient methods using Me2NSO2Cl/ Me2NR and p-TsCl/N-methylimidazole. (iii) As a promising method for the replacement of conventional pyridine-method, we introduce efficient pyridine-free improved methods, which utilize sterically uncrowded tertiary amines such as Me3N·HCl/Et3N and Me2N (CH2) nNMe2 as a key protocol. (iv) We introduce highly powerful, neutral, and catalytic methods for silylations of alcohols (giving enol ethers) and ketones (giving enol silyl ethers) using hydrosilanes, disilanes, and silazanes.

We have developed an efficient method for the esterification or thioesterification of equimolar amounts of carboxylic acids and alcohols or thiols using a novel reagent, p-toluenesulfonyl chloride (TsCl) together with N-methylimidazole. The present method is simple, mild, and reactive, uses readily available and economical reagents. The choice of amine is critical for the present method. The amine, N-methylimidazole, has two roles: (i) as an HCl scavenger for the initial smooth generation of mixed anhydrides between carboxylic acids and TsCl and (ii) successive formation of highly reactive ammonium intermediates from mixed anhydrides. This method could be applied to various types of carboxylic acids, alcohols, and thiols: a) several functionalities were tolerated; b) two N-Cbz amino acids were smoothly esterified without racemization; and c) the labile 1β-methylcarbapenem key intermediate and a pyrethroid insecticide, prallethrin, were successfully prepared. The related amide formation between carboxylic acids and primary or secondary amines was also performed. The proposed reaction mechanism involves a novel method for producing the reactive acylammonium intermediates. The production of these intermediates was rationally supported by a careful 1H NMR monitoring study.

An asymmetric 1,4-addition reaction of 5H-oxazol-4-ones to alkynones using chiral guanidine catalysts bearing a hydroxy group at the appropriate position was developed, and applied to several subst...