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Pyridine-3-carboxylic anhydride (3-PCA) was found to function as an efficient coupling reagent for the preparation of carboxylic esters from various carboxylic acids with alcohols under mild conditions by a simple experimental procedure. This novel condensation reagent 3-PCA was applicable not only for the synthesis of achiral carboxylic esters catalyzed by 4-(dimethylamino)pyridine (DMAP) but also for the production of chiral carboxylic esters by the combination of chiral nucleophilic catalyst, such as tetramisole (=2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b][1,3]thiazole) derivatives. An efficient kinetic resolution of racemic benzylic alcohols with achiral carboxylic acids was achieved by using 3-PCA in the presence of (R)-benzotetramisole ((R)-BTM), and a variety of optically active carboxylic esters were produced with high enantiomeric excesses by this new chiral induction system without using a tertiary amine.

Preparation of alkyl aryl sulfides from alcohols and arenethiols such as 2-sulfanyl-1,3-benzothiazole (BtzSH) is described by a new type of oxidation–reduction condensation using phenyl diphenylpho...

(Chloromethylene)dimethylammonium chloride (Vilsmeier reagent) works as an efficient condensation reagent in the formation of carboxylic esters from carboxylic acids and alcohols under mild conditions in a one-pot procedure. Secondary alcohols are converted successively into the corresponding esters in moderate to high yields with inversion of configurations.

A highly useful method for the preparation of carboxylic esters and carboxamides from various carboxylic acids was established by using a novel condensing reagent, pyridine-3-carboxylic anhydride (...

Chiral quaternary ammonium phenoxides were prepared readily from commercially available cinchona alkaloids and employed as novel useful asymmetric organocatalysts. Among these chiral quaternary ammonium phenoxides, a cinchonidine-derived phenoxide that possesses a sterically hindered N(1)-3,5-bis[3,5-bis(trifluoromethyl)phenyl]benzyl group was the most effective for asymmetric trifluoromethylation. In the presence of a catalytic amount of Lewis bases, such as cinchonidine-derived quaternary ammonium phenoxides, catalyzed the reaction of various ketones with (trifluoromethyl)trimethylsilane to afford the corresponding trifluoromethylated adducts in high yields and with moderate to high enantioselectivities.

A novel method for the preparation of alkyl azides from alcohols by way of oxidation–reduction condensation is described. In this reaction, the sterically-hindered tert-alkyl phosphinites that are prepared from the corresponding alcohols are converted into tert-alkyl azides with almost complete inversion of their stereochemistry: the obtained alkyl azides are then successfully reduced to afford the corresponding amines on treatment with LiAlH4, thus, a versatile method for the preparation of chiral amines from the corresponding chiral alcohols is established.

A convenient method for the Cu(II)-catalyzed O-phenylation of tertiary alcohols with organobismuth(V) compounds under mild conditions is described. Functionalized tertiary alcohols such as α-hydroxy carbonyl compounds were phenylated by using either Ph3Bi(OAc)2 or tetraphenylbismuth compounds. In the cases of O-phenylation of simple tertiary alcohols, the use of tetraphenylbismuth fluoride (Ph4BiF) was particularly effective and gave various tert- alkyl phenyl ethers in high yields. The synthesis of alkyl phenyl ethers from primary and secondary alcohols are also described.

An alkylation reaction of alcohols with alkyl N-(methylsulfonyl)diphenylphosphinimidates proceeded smoothly in the presence of a catalytic amount of trimethylsilyl triflate (Me3SiOTf) in DME at roo...

Lewis base-catalyzed perfluoroalkylation of carbonyl compounds and aldimines with (perfluoroalkyl)trimethylsilanes (TMSCF3, TMSC2F5, and TMSC3F7) is described. The nitrogen- or oxygen-containing an...

Lewis base catalyzed Mannich-type reaction between trimethylsilyl enol ethers and N-tosylaldimines is described. Nitrogen anions generated from amides or imides such as lithium benzamide or potassium phthalimide are found to be effective Lewis base catalysts in DMF at room temperature to afford the corresponding beta-amino carbonyl compounds in good to high yields; the oxygen anion generated from carboxylic acids such as lithium acetate was also found to be effective in dry DMF. The above-mentioned lithium acetate-catalyzed Mannich-type reaction between aldimines and various trimethylsilyl (TMS) enol ethers such as silyl ketene acetal proceeded smoothly even in water-containing DMF. Then, Lewis base catalyzed three-component Mannich-type reactions of TMS enol ether, tosylamide, and aromatic aldehyde having electron-withdrawing group such as p-nitrobenzaldehyde were investigated. The reaction proceeded smoothly to afford the corresponding beta-amino ester in good yield. Further, ammonium carboxylates such as tetrabutyl ammonium acetate or tetrabutyl ammonium benzoate were found to be more effective Lewis base catalysts in the above-mentioned Mannich-type reaction. The synthesis proceeded in various solvents at lower temperatures. The reaction between aldimines and TMS enol ethers generated from thioester and various ketones such as propiophenone or cyclohexanone also proceeded smoothly to afford the corresponding beta-amino carbonyl compounds in high yields with good to high anti-selectivities.

Oxidation–reduction condensation between 2-sulfanyl-1,3-benzothiazole (Btz-SH) and the alkyl diphenylphosphinites 1, prepared from tertiary alcohols, proceeded smoothly in the presence of 2,6-di-t-...

An efficient and concise synthesis of the β-Man(1→4)GlcN linkage that exists in N-linked glycans has been established. Direct β-mannosylations of the 4-OH group of glucosamine derivatives by using ...

The esterification of carboxylic acids with alcohols by using di-2-thienyl carbonate (2-DTC) in the presence of a catalytic amount of 4-(dimethylamino)pyridine (DMAP) proceeded smoothly to afford t...

The samarium(II) iodide-mediated stereoselective aldol reactions of acylaziridines with aldehydes are described. β-Amino-β'-hydroxy ketones were synthesized in high yields by the aldol reaction of aldehydes with samarium enolates generated by aziridine-fragmentation of aziridinyl ketones with two moles of samarium(II) iodide. By the choice of an appropriate nitrogen protecting group, depending on the substituent at C-3 position of aziridinyl ketone, anti,anti-β-ami-no-β'-hydroxy ketones were diastereoselectively obtained among the four possible diastereomers. Further, enantiomerically pure anti,anti-β-amino-β'-hydroxy ketones were successfully obtained by this aldol reaction when chiral aziridinyl ketones were used. In addition, δ-amino-β'-hydroxy-β,γ-unsaturated esters were also synthesized in high yields by the aldol reaction of aldehydes with samarium enolates generated by aziridine-fragmentation and olefin-migration of γ,δ-aziridinyl-α,β-unsaturated esters using two moles of samarium(II) iodide. This aldol reaction proceeded with complete α-regioselectivity and formed (E)-olefin selectively. By introducing chiral oxazolidin-2-one auxiliary to γ,δ-aziridinyl-α,β-unsaturated carbonyl system, this reaction was extended successfully to the asymmetric reaction and enantiomerically pure syn-δ-amino-β'-hydroxy-β,γ-unsaturated esters were obtained in high yields.

Michael reactions between trimethylsilyl enolates and α,β-unsaturated carbonyl compounds by using a Lewis base catalyst such as lithium benzamide 4 or lithium succinimide 5 in DMF proceeded smoothl...

A new-type of oxidation–reduction condensation using alkyl diphenylphosphinites 1 and 2,6-di-tert-butyl-1,4-benzoquinone (DBBQ) proceeded smoothly under mild and neutral conditions by using nucleophiles such as nitrogen-, carbon- or sulfur-ones whose pKa values were lower than 14. Various chiral molecules were successfully synthesized from chiral secondary or tertiary alkyl diphenylphosphinites in good to high yields with inversion of stereochemistry via SN2 displacement. Effects of the substituents of 1,4-benzoquinones and the pKa values of nucleophiles on these reactions have been investigated in detail. (Contributed by Teruaki MUKAIYAMA, M.J.A.)

Oxidation–reduction condensation using in situ formed alkoxydiphenylphosphines, 2,6-dimethy-1,4-benzoquinone, and carboxylic acids provides a useful method for the preparation of inverted tertiary ...

Lithium acetate (AcOLi)-catalyzed aldol reactions between trimethylsilyl enolates and aldehydes proceed smoothly in anhydrous DMF or pyridine to afford the corresponding aldols in good to high yiel...

Aldol reactions between trimethylsilyl ketene acetals and aldehydes by using a catalytic amount of alkoxide anion proceeded smoothly to afford the corresponding aldols in DMF, indicating that the initially-formed aldolate anion effectively worked to catalyze the reaction. The “product-catalyzed aldol reaction”, a new class Lewis base-catalyzed aldol reaction, between trimethylsilyl ketene acetals and aldehydes was performed successfully by the use of aldolate anion as a Lewis base catalyst.

Oxidation-reduction condensation via alkoxydiphenylphosphines (diphenylphosphinite esters) (1), generated in situ from chlorodiphenylphosphine (2) and alcohols, 2,6-dimethyl-1,4-benzoquinone (3), and phenols proceeds smoothly to afford alkyl-aryl ethers in good to high yields under neutral conditions. In a similar fashion, a new and efficient method for the preparation of symmetrical or unsymmetrical dialkyl ethers in good to high yields is established via tetrafluoro-1,4-benzoquinone (fluoranil) (4), alcohols, and 1 formed in situ from (n)BuLi-treated alcohols and 2. This method is applicable also to the etherification of chiral secondary or tertiary alcohols with retention or inversion of configurations. The inverted ethers are afforded by treating chiral alkoxydiphenylphosphines and achiral alcohols, while the reaction of achiral alkoxydiphenylphosphines and chiral alcohols forms retained ethers.

Highly β-selective glucosylations of glycosyl acceptors having a primary hydroxy group with a 6-nitro-2-benzothiazolyl α-glucoside donor 3α proceeded smoothly in the presence of a catalytic amount ...

A convergent total synthesis of F1α antigen, a member of the tumor-associated O-linked mucin glycosyl amino acid, was tried by one-pot sequential glycosylation. Highly α-selective glycosylation of amino acid 7 with thioglycoside 6 was successfully carried out by combining trityl trifluoromethanesulfonate (TrOTf) and N-iodosuccimide (NIS) which gave glycosyl amino acid 21 in high yield (97%, α/β = 83⁄17). Next, the glycosylation of thioglycoside 4 with galactosyl phenyl carbonate 2 or fluoride 3 was tried by the promotion of trityl tetrakis(pentafluorophenyl)borate [TrB(C6F5)4] or trifluoromethanesulfonic acid (TfOH); protected F1α 25 was afforded in 80 or 89% overall yield, respectively, by the further addition of glycosyl amino acid 5 and NIS. The desired trisaccharide was obtained in high yield after removal of the protecting groups. Next, a convergent total synthesis of branched hepta-β-glucoside 30 having phytoalexin-elicitor activity was efficiently performed by way of two one-pot sequential glycosyl...

N-tert-Butylbenzenesulfenamide ( 1 )-catalyzed oxidation of various primary and secondary alcohols to the corresponding aldehydes and ketones was efficiently carried out by using N-chlorosuccinimide (NCS) in the coexistence of potassium carbonate and molecular sieves 4 A at easy-to-control temperatures ranging from 0°C to room temperature. The present catalytic oxidation was performed without giving any damage to the functional groups in alcohols, and was particularly effective in the oxidation of alcohols that formed labile aldehydes because of its mild reaction conditions. Further, selective oxidation of primary hydroxy groups took place in 1 -catalyzed oxidation of several diols. Mechanistic investigation suggested that the chlorination of the sulfenamide 1 by NCS led to the formation of a key species, N-tert-butylbenzenesulfinimidoyl chloride ( 2 ), which in turn oxidized alcohols in the presence of potassium carbonate to afford carbonyl products by accompanying regeneration of the catalyst 1 .

A novel and efficient glycosyl donor having a p-trifluoromethylbenzylthio-N-p-trifluoromethylphenylformimidate group at an anomeric position is easily prepared by the addition of anomeric hydroxy group of 2,3,4,6-tetra-O-benzyl-α,β-D-glucopyranose to p-trifluoromethylphenyl isothiocyanate, followed by treatment with p-trifluoromethylbenzyl bromide. Catalytic and stereoselective glycosylation of various glycosyl acceptors with the above glycosyl donor smoothly proceeds by using various protic and Lewis acid catalysts which interact with its nitrogen atom. Further, catalytic and highly 1,2-cis or 1,2-trans stereoselective and chemoselective glycosylation between two different “armed” and “disarmed” glycosyl p-trifluoromethylbenzylthio-N-p-trifluoromethylphenylformimidates is also performed effectively in the presence of a catalytic amount of trifluoromethanesulfonic acid (TfOH) at −78 °C in tBuOMe or EtCN, respectively. These glycosylations are applied to successful one-pot sequential syntheses of trisaccha...

Optically active β-ketoiminato cobalt complexes were recently developed as high performance catalysts for eanantioselective borohydride reduction of aromatic ketones or imines to afford the optically active alcohols or amines with high enantiomeric excesses. This enantioselective reduction is carried out using a precisely pre-modified borohydride with alcohols such as tetrahydrofurfuryl alcohol, ethanol and methanol, and high optical yields are realized by choosing the appropriate alcohol as modifiers and a suitable β-ketiominato ligand of the catalyst. The enantioselective borohydride reduction has been successfully applied to the efficient preparations of optically active 1, 3-diaryl-1, 3-propanediols, the stereoselective reduction of diacylferrocenes, and the dynamic and/or kinetic resolution of 1, 3-dicarbonyl compounds to afford the corresponding optically active anti-aldol compounds. In the presence of a catalytic amount of the cobalt complex and modified borohydride, the asymmetric 1, 4-reduction of β, β-disubstituted α, β-unsaturated carboxamides proceeded with high enantioselectivity, and the 1, 4-reduction of the α-substituted α, β-unsaturated carboxamides followed by enantioselective in situ protonation smoothly proceeded to afford the optically active α-substituted carboxamides with good enantiomeric excesses.

A catalytic and stereoselective glycosylation of various glycosyl acceptors, such as methyl glycosides, thioglycosides, or a disarmed glycosyl fluoride, with benzyl-protected armed glycosyl fluoride was successfully carried out by using various protic acids in the presence of MS 5A. In the cases when trifluoromethanesulfonic acid (TfOH) or perchloric acid (HClO4) was used in diethyl ether (Et2O), α-glycosides were obtained as major products, while β-stereoselectivity was observed when tetrakis(pentafluorophenyl)boric acid [HB(C6F5)4] was used in a mixed solvent of trifluoromethylbenzene (BTF)–pivalonitrile (tBuCN) = 5 : 1. Stereoselectivity of this glycosylation was controlled by the properties of counter anions of the catalyst as well as by those of solvents. Also, one-pot trisaccharide synthesis was performed by successive addition of NIS and third-sugar to afford Glcα or β1–6Glcβ1–6Glc and Glcα or β1–6GlcNβ1–6Glc in excellent yields.

Various primary and secondary alcohols were smoothly oxidized to the corresponding aldehydes and ketones by using a new oxidizing agent, N-t-butylbenzenesulfinimidoyl chloride (4a), in the coexistence of DBU or zinc oxide. The present oxidation proceeded under mild conditions via five-membered intramolecular proton-transfer of an alkyl arenesulfinimidate intermediate.

Direct iodination and bromination of various aromatic compounds with 1.1–2.0 molar amounts of iodine monochloride (ICl) and 1.1–3.0 molar amounts of bromine proceeded smoothly to afford the corresponding aromatic iodides and bromides, respectively, in good to excellent yields by using 0.05 molar amount of ferrocenium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, Cp2FeB[3,5-(CF3)2C6H3]4 (1), in the presence of ZnO. Iodination of toluene in the coexistence of 0.5 molar amount of DDQ also proceeded to give iodotoluenes in high yield.

N-tert-Butylbenzenesulfenamide (1) catalyzed oxidation of various alcohols with stoichiometric amount of anhydrous chloramines-T (2) proceeded smoothly at room temperature to afford the corresponding carbonyl compounds in good yields.

Reductive coupling reaction of aromatic and aliphatic aldehydes proceeded under mild conditions to give the corresponding pinacols in moderate to high yields and dl -diastereoselectivities by using combinations of either low valent titanium(II) bromide and copper or titanium(IV) iodide and copper in a mixed solvent of dichloromethane and pivalonitrile. In the case of using titanium(IV) iodide and copper, pinacols were obtained in good to high yields with moderate to high diastereoselectivities irrespective of the number of substitutuents at α-position of aliphatic aldehydes.

An effective method for the preparation of 8-membered ring enone, (4S,5R,7R,8R)-4,8-bis(benzyloxy)-7-(t-butyldimethylsiloxy)-5-(4-methoxybenzyloxy)-2,6,6-trimethylcyclooct-2-enone (1), in sufficien...

Direct iodination reaction of several aromatic compounds with 1.1–2.0 molar amounts of iodine monochloride (ICl) proceeded smoothly to afford the corresponding aromatic iodides in good to excellent yields by using 5 mol% of Cp2FeB[3,5-(CF3)2C6H3]4 (1) in the coexistence of DDQ or ZnO.

Preparations of carboxamides and peptides are performed in high yields from free carboxylic acids and amines by dehydration condensation using di(2-pyridyl) carbonate (DPC) or O,O′-di(2-pyridyl) thiocarbonate (DPTC) in the presence of a catalytic amount of 4-(dimethylamino)pyridine (DMAP). The formation of 2-pyridyl esters, key intermediates of the reaction, from carboxylic acids by using DPC proceeded faster than by using DPTC; therefore, the former carbonate is more efficiently employed in the above condensation reactions.

Highly diastereoselective aldol reactions of α-bromo ketones with several aldehydes were successfully carried out by using a combination of titanium(II) chloride and copper or sodium iodide in dichloromethane-pivalonitrile at low temperature. Similarly, Reformatsky reactions of α-bromo thioester with aliphatic aldehydes proceeded to afford β-hydroxy thioesters in good yields under mild conditions.

A catalytic and stereoselective glycosylation of several glycosyl acceptors with β-D-glycosyl fluoride was successfully performed in the presence of a catalytic amount of trityl tetrakis(pentafluorophenyl)borate (TrB(C6F5)4) or trifluoromethanesulfonic acid (TfOH). When TrB(C6F5)4 was used as a catalyst in the solvent pivalonitrile/(trifluoromethyl)benzene 1 : 5, the glycosylation proceeded smoothly to afford the glycosides in high yields with high β-D-stereoselectivities (see Table 3). Further, the glycosylation by the armed-disarmed strategy in the presence of this catalyst was established (see Table 4). Similarly, glycosylation catalyzed by the strong protic acid TfOH afforded the corresponding β-D-glycosides in good-to-excellent yields on treating β-D- glycosyl fluorides having a 2-O-benzoyl group with various glycosyl acceptors including thioglycosides (see Tables 6 and 7).

The reductive coupling reaction of aldehydes and ketones, including unsymmetrical aliphatic ketones, proceeded smoothly to give the corresponding pinacols in good to high yields under mild conditions by using combination of titanium(II) chloride and zinc or titanium(IV) chloride and zinc in dichloromethane-pivalonitrile. Meso-selective formation of the coupling products was observed in the cases of some aliphatic ketones. The diastereoselectivities of coupling products depend on both difference of bulkiness of 2-, and 2'-substituents of carbonyl group of the reactant, and overall steric effect around the carbonyl groups.Key words: diastereoselective pinacol reaction, dichloromethane-pivalonitrile, titanium(II) chloride, titanium(IV) chloride, zinc.

Carboxamides are prepared in high yields by dehydration condensation between nearly equimolar amounts of free carboxylic acids and amines both of which involve secondary or tertiary alkyl substituted ones with O,O'-di(2-pyridyl) thiocarbonate, a coupling reagent, in the presence of a catalytic amount of 4-(dimethylamino)pyridine.

A new class of cobalt complexes with optically active N,N′-ethylenebisketoiminato ligands was synthesized, and one of them was fully characterized by X-ray crystallographic analysis. These cobalt(II) complexes proved to be efficient catalysts in enantioselective borohydride reduction of aryl ketones, phosphinyl imines, and β,β-disubstituted α,β-unsaturated carboxylates. It was found that the enantiofacial discrimination in the borohydride reduction was influenced by the structure of the diphenylethylenediamine moiety of the cobalt complex catalysts.

A new method for the total asymmetric synthesis of antitumor agent Taxol is described. Baccatin III, a complex carbon framework, is synthesized by way of B to BC to ABC ring construction. Further, a method of forming Taxol from baccatin III and a β-amino acid is also demonstrated.

Optically active aldiminato cobalt(II) complexes have been found to catalyze the enantioselective reduction of ketones with sodium borohydride affording the corresponding optically active secondary alcohols in high chemical yields with high enantioselectivities. The enantioselective borohydride reduction is also applicable to not only C=O bonds in aromatic ketones but also to C=N bonds in aromatic imines.

Chiral allylating reagents, readily generated in situ from tin(II) catecholate [SnII(O2C6H4)], allyl halides, chiral dialkyl tartrates, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), reacted smoothly with aldehydes or reactive ketones at −78 °C in the presence of a catalytic amount of copper salts to afford the corresponding optically active homoallyl alcohols. Allylation of aromatic aldehydes and pyruvates by the present chiral tin reagents proceeded in high yields (81—99%) with high enantioselectivities (89—94%ee). In addition, both enantiomers of dimethyl citramalate were prepared from the allylation products of benzyl pyruvate.

Living cationic ring-opening polymerization of e-caprolactone (CL), δ-valerolactone (VL) and 1,3-dioxepane-2-one (6) was achieved at room temperature by using zirconocene borate complex catalysts. Respective block copolymerization of CL with VL or with cyclic carbonate 6 was also successfully performed. The mechanism of the present cationic living polymerization is discussed.

入手容易な原料から対応する1,2-ジアミンを簡便に合成する反応の開発を目的として,ニトロオレフィンにアミノ基等価体をMichael付加させた後,得られた付加体を還元して1,2-ジアミンへ変換する方法について検討した.その結果,アンモニアあるいはペソジルアミンをアミノ基等価体とした場合には満足できる結果が得られないのに対し,O-アルキルヒドロキシルアミンを用いると対応する1,2-ジアミンが収率良く得られることがわかった.すなわち,ニトロオレフィンとO-アルキルヒドロキシルアミンから調製した付加体をパラジウム触媒存在下で水添還元すると目的とする1,2-ジアミンに誘導できる.さらに,この付加と還元の二段階の反応はワンポットで完結できることがわかり,合成プロセスの簡便化に成功した.この1,2-ジアミンの簡便合成法は種々のニトロオレフィンに適用可能であり,適切なパラジウム触媒を選択することによって最高収率92%で対応する1,2-ジアミンを得ることができる.

Construction of the AB-ring system of the taxane framework via an A-ring annulation strategy was demonstrated by base-mediated intramolecular aldol reaction of (Z)-2,2-dimethyl-3-(1-methyl-2-oxopropylidene)cyclooctanone, affording the title compound, 1-hydroxy-8,11,11-trimethylbicyclo[5.3.1]undec-7-en-9-one. A cyclization precursor, the tetra-substituted (Z)-alkene, was prepared from the corresponding cyclooctanone derivative, 3-[(alpha,alpha- dimethylbenzyl)dimethylsiloxy]-2,2-dimethylcyclooctanone via a bicyclic alpha,beta-unsaturated lactone intermediate.

Transglycosylation of methyl glycosides with various glycosyl acceptors using a Sn(OTf)2–Me3SiCl promoter system in the presence of molecular sieves 5A afforded the corresponding glycosides. Several useful disaccharides are effectively prepared in good yields with moderate to good stereoselectivities.