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After initially establishing a novel cyclization reaction of ω-hydroxycarboxylic acids (seco-acids) using 4-trifluoromethylbenzoic anhydride (TFBA) and Lewis acid catalysts to form the correspondin...

We report an effective dynamic kinetic resolution (DKR) system of racemic 2-(1H-pyrrol-1-yl)alkanoic acids, which consists of a rapid racemization step via an activating substrate and an enantio-di...

A variety of optically active 1-heteroarylalkanols and their esters, which include heteroaromatic moieties, such as 2-furyl, 2-thienyl, 3-thienyl, 2-thiazoyl, 2-benzothiazoyl, and 2-benzoxazoyl gro...

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...

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.

An efficient method for the synthesis of macrolides directly from ω-hydroxycarboxylic acids is established by using 4-(trifluoromethyl)benzoic anhydride and a catalytic amount of active titanium(IV) salts together with chlorotrimethylsilane under mild conditions.

Various carboxylic esters are prepared in excellent yields from nearly equimolar amounts of free carboxylic acids and alcohols at room temperature by combined use of 4-(trifluoromethyl)benzoic anhydride and a catalytic amount of active titanium(IV) salt together with chlorotrimethylsilane.

In the presence of a catalytic amount of active titanium(IV) salt generated in situ from 1 mol of TiCl4 and 2 mol of AgOTf, weakly nucleophilic anilines react under mild conditions with nearly equimolar amounts of silyl carboxylates to afford the corresponding anilides in excellent yields using 4-(trifluoromethyl)benzoic anhydride. The mixed anhydride formed in situ from trimethylsily acetate and 4-(trifluoxomethyl)benzoic anhydride, a key intermediate of this reaction, was detected by 1H NMR experiment. Further, it was shown that the reaction of the mixed anhydrides and 2-nitroaniline was faster than that of the corresponding homo anhydrides and 2-nitroaniline.

In the presence of a catalytic amount of Lewis acid, various carboxylic esters or S-phenyl carbothioates are prepared in excellent yields by the respective reactions of equimolar amounts of silyl carboxylates and alkyl silyl ethers or phenyl silyl sulfides with 4-trifluoromethylbenzoic anhydride.

The lactonization of silyl ω-siloxycarboxylates is successfully carried out under mild conditions in good to high yields by using p-trifluoromethylbenzoic anhydride and a catalytic amount of active acidic species generated in situ from TiCl4 and AgClO4.

In the presence of a catalytic amount of titanium(IV) salt, various S-phenyl carbothioates are prepared in excellent yields by the reaction of nearly equimolar amounts of silyl derivatives of carboxylic acids and benzenethiols with p-trifluoromethylbenzoic anhydride.

Various carboxylic esters are prepared in excellent yields by the reaction of nearly equimolar amounts of silyl derivatives of carboxylic acids and alcohols with p-trifluoromethylbenzoic anhydride in the presence of a catalytic amount of Lewis acid.

Optically active α-alkoxy-α-methyl-β-hydroxy ester derivatives are prepared starting from racemic α-alkoxy propionic acid ester derivatives by way of asymmetric aldol reaction of the corresponding achiral intermediates. (−)-2-C-Methyl-D-threono-1,4-lactone is conveniently synthesized by using this methodology.

syn-α,β-Dihydroxy thioesters are prepared in good yields with high diastereo- and enantioselectivities by the asymmetric aldol reaction of 1-trimethylsiloxy-1-ethylthio-2-t-butyldimethylsiloxyethene with aldehydes using a chiral promoter consisting of tin(II) triflate, a chiral diamine and dibutyltin diacetate.

Three types of sugars, 6-deoxy-L-tallose,4-C-methyl-D-ribose, and D-ribose were synthesized from both achiral starting materials, α,β-unsaturated aldehydes and silyl enol ethers of α-benzyloxy thioesters, by successive asymmetric aldol and vicinal dihydroxylation reactions.

Anti-α,β-dihydroxy thioesters are prepared with excellent enantioselectivities by the asymmetric aldol reaction between both achiral aldehydes and silyl enol ethers derived from α-benzyloxy thioesters in the presence of a chiral promoter consisted of chiral diamine coordinated tin(II) triflate and dibutyltindiacetate.

Highly enantioselective aldol reaction of silyl enol ethers with aldehydes is performed by the use of a catalytic amount of chiral diamine coordinated tin(II) triflate according to a slow addition procedure.

The simple and efficient synthesis of lasofoxifene (4), a possible candidate for alleviating osteoporosis, via the novel three-component coupling reaction among 4-pivaloyloxybenzaldehyde (5), cinna...

Various carboxylic esters were obtained in excellent yields with high chemoselectivities from nearly equimolar amounts of carboxylic acids and alcohols using 2-methyl-6-nitrobenzoic anhydride with triethylamine in the presence of a catalytic amount of 4-(dimethylamino)pyridine.

Various optically active secondary alcohols are obtained by asymmetric alkylation of aldehydes with diethylzinc by way of a new catalyst system, ((R)-thiolan-2-yl)diphenylmethanol and several metal alkoxides. The transition states are also discussed in terms of experimental results and theoretical calculation.

Unsymmetrical alkyl 2-hydroxy-1-(1-hydroxyalkyl)alkyl ketones (bis-aldols) are successfully synthesized by way of sequential two aldol reactions using α-bromo ketones and two different aldehydes. In the first reaction, α-bromo-β-stannyloxy ketones are formed by tin(II) trifluoromethanesulfornate-promoted aldol reaction of α-bromo ketones with several aldehydes. Bis-aldols are then formed via the second aldol reaction between another aldehydes and dianionic enolates generated by the reduction of α-bromo-β-metalloxy ketones with titanium(IV) iodide and copper.

Unsymmetrical alkyl or aryl 2-hydroxy-1-(1-hydroxyalkyl)alkyl ketones (bis-aldols) were synthesized by the samarium(II) iodide-mediated aldol reaction of aldehydes with alkyl or aryl oxiranyl ketones. Bis-aldols were formed via the aldol reaction of aldehydes with samarium enolates generated by epoxy-fragmentation of oxiranyl ketones using two moles of samarium(II) iodide.

1,1-Dichloroethyllithium (5), generated by treating 1,1-dichloroethane (4) with lithium diisopropylamide (LDA) or n-butyllithium, reacted with alkyl carboxylates to afford the corresponding α,α-dichloro- or α-monochloro-ethyl ketones selectively in good to high yields. According to the above alkylation method, synthetic intermediates of Taxol, optically active α,α-dichloroethyl polyoxyketone 2 and α-chloroethyl polyoxyketone 3, were respectively synthesized from optically active methyl polyoxycarboxylate 1 in good yields.

Highly diastereoselective aldol reaction of α-bromo ketones with aliphatic aldehydes was successfully carried out by using titanium(II) chloride and copper in dichloromethane at low temperature. Similarly, Reformatsky-type reaction of α-bromo thioester with aliphatic aldehydes was promoted under mild conditions to afford β-hydroxy thioesters in good to moderate yields.

An effective method for the preparation of 8-membered ring enone 1 in sufficient quantities was developed. First, optically active trialkoxyaldehyde 3 was prepared by diastereoselective dihydroxylation of olefin 7 derived from D-pantolactone. Secondly, 8-chloro-7-oxoaldehydes 20α,β were newly synthesized by the following reactions: namely, MgBr2·OEt2-mediated diastereoselective aldol reaction of the aldehyde 3 with ketene (trimethylsilyl) acetal 15, direct 1,1-dichloroethylation of ester 17 with 1,1-dichloroethyllithium, and partial dehalogenation of the resulting α,α-dichloroethyl ketone 18 with nBu3SnH. Lastly, the chiral 8-chloro-7-oxoaldehydes 20α,β were converted to the 8-membered ring enone 1 by SmI2-mediated aldol cyclization.

Crossed aldol reaction of enol esters, stable carbon nucleophiles, with carbonyl compounds is effectively performed by the promotion of diethylaluminum ethoxide under mild conditions. This reaction is applicable not only to simple enol esters but also to lactones such as α-angelicalactone.

Optically active novel 18-demethyltaxiods were successfully synthesized from 2α,10β-dibenzyloxy-11β-(t-butyldimethylsiloxy)-7β-hydroxy-1α-(p-methoxybenzyloxy)-8β,15,15-trimethyl-4-methylene-trans-bicyclo[6.4.0]dodecan-9-one (2) which corresponds to the BC ring system of Taxol by stereoselective allylation and intramolecular aldol condensation reactions.

Stereoselective Diels-Alder reaction between several α,β-unsaturated ketones and acetoxy-1,3-butadienes is effectively performed by the promotion of diethylaluminum ethoxide under mild conditions. This reaction is successfully applied to the synthesis of optically active bicyclo[6.4.0]dodecanone 9 which corresponds to the BC ring system of 10-deoxy taxane derivatives from the 8-membered ring enone 7 and diene 2.

The reductive coupling reaction of aromatic and aliphatic ketones including acyclic aliphatic ketones proceeded smoothly to give the corresponding pinacols in good to high yields below room temperature by the combined use of titanium(II) chloride and zinc in the presence of pivalonitrile. Meso-selective formation of the coupling products was observed in the cases with some acyclic aliphatic ketones.

An efficient method for the synthesis of (−)-cephalosporolide D was established via successive enantioselective aldol reaction and effective construction of 8-membered ring lactone moiety.

Various carboxylic esters were obtained in high yields from free carboxylic acids and several alcohols including bulky ones by using O,O′-di(2-pyridyl) thiocarbonate and a catalytic amount of DMAP.

Baccatin III was efficiently synthesized from the BC ring system of Taxol,2α,10β-dibenzyloxy-11β-(t-butyldimethylsil-oxy)-7β-hydroxy-1α-(4-methoxybenzyloxy)-8β,15,15-trimethyl-4-methylene-trans-bic...

Total asymmetric synthesis of Taxol was completed by dehydration condensation between a protected N-benzoylphenylisoserine 4 or 9 and 7-TES baccatin III which was prepared from 8-membered ring enone. Taxol side chains 4, 7, 9 and 11, optically active protected N-benzoylphenylisoserines, were successfully synthesized by enantioselective aldol reaction from two achiral starting materials, benzaldehyde and an enol silyl ether derived from S-ethyl benzyloxyethanethioate.

Optically active 2α,10β-dibenzyloxy-11β-(t-butyldimethylsiloxy)-7β-hydroxy-1α-(4-methoxybenzyloxy)–8β,15,15-trimethyl-4-methylene-trans-bicyclo[6.4.0]dodecan-9-one 2 that corresponds to BC ring system of Taxol was prepared from 8-membered ring enone 3 in high yield via stereoselctive Michael addition and successive intramolecular aldol cyclization. The above 8-membered ring enone 3 was synthesized from the linear optically active polyoxy-compound 4 by SmI2-mediated intramolecular aldol cyclization.

Optically active novel taxoids were efficiently synthesized from 8-membered ring compound 3 by successive constructions of BC and ABC ring systems via each intramolecular aldol and intramolecular pinacol coupling reactions.

Medium-sized lactones are prepared in good yields on treating monomeric cyclic silyl siloxycarboxylates, prepared in situ from ω-hydroxycarboxylic acids and 1,2-bisdimethylsilylbenzene using RhCl(PPh3)3 catalyst, with an active catalyst of dimethylsilylbis(trifluoromethanesulfonate).

Optically active 1α-allyl-1β,11β-benzylidenedioxy-2α,10β-bis(benzyloxy)-7β,9β-isopropylidenedioxy-8α,12,12-trimethyl-4-methylenebicyclo[6.4.0]dodecane (2)1 which corresponds to BC ring system of 8-epitaxoids was prepared in high yield form ketoaldehyde 8 via intramolecular aldol cyclization and succesive stereoselective methylation reactions. The ketoaldehyde 8 was synthesized from 8-membered ring compound 3 by stereoselective Michael addition using higher-order cuprate.

Optically active 9-t-butyldiphenylsiloxy-11,11-dimethyl-5-methoxymethoxy-1,2,6-tribenzyloxybicyclo[5.3.1]undec-3,7-diene (12) was synthesized from diketone 9 via an intramolecular aldol reaction. The diketone 9 was synthesized from 7-t-butyldimethylsiloxy-4,8-dibenzyloxy-6,6-dimethyl-5-p-methoxy-benzyloxy-2-cycloocten-1-one (1) by way of a two-step sequence using diastereoselective allylation with allylmagnesium bromide followed by Wacker oxidation.

Optically active 3,7-dibenzyloxy-4,8-di-t-butyldimethylsiloxy-5,5-dimethyl-6-p-methoxybenzyloxy-2-octanone (2) has been synthesized by way of diastereoselective aldol reaction between 4-benzyloxy-5-t-butyldimethylsiloxy-2,2-dimethyl-3-p-methoxy-benzyloxypentanal (3) and ketene silyl acetal 4 using MgBr2·OEt2 as a catalyst. The chiral pentanal 3 was synthesized either by asymmetric aldol reaction of both prochiral aldehyde 5 and ketene silyl acetal 4 using a chiral Lewis acid or by diastereoselective aldol reaction between the chiral aldehyde 6 derived from L-serine and the lithium enolate derived from methyl isobutyrate.

Optically active 7-t-butyldimethylsiloxy-4,8-dibenzyloxy-6,6-dimethyl-5-p-methoxybenzyloxy-2-cycloocten-1-one (1) was synthesized from 3,7-dibenzyloxy-4,8-di-t-butyldimethylsiloxy-5,5-dimethyl-6-p-methoxybenzyloxy-2-octanone (2) by way of intramolecular Reformatsky-type reaction using SmI2.

1-t-Butyldimethylsiloxy-8,11,11-trimethylbicyclo[5.3.1]undec-7-en-9-one (2) has been synthesized via intramolecular aldol condensation of the precursor 3 by combined use of lithium diisopropylamide (LDA) and CeCl3. The dicarbonyl compound 3 was prepared by allylation of 8-membered ring ketone 6b.

Various carboxylic esters are prepared in good to high yields from equimolar amounts of free carboxylic acids and alcohols by the combined use of octamethylcyclotetrasiloxane and a catalytic amount of TiCl(OTf)3.

Catalytic Diels-Alder reactions between several 1,3-dienes and α,β-unsaturated ketones are effectively promoted by the combined use of diphenyltin sulfide (Ph2Sn=S) and silver perchlorate or Lawesson’s reagent (2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide) and silver perchlorate under mild conditions.

Various carboxanilides are prepared in excellent yields from nearly equimolar amounts of silyl carboxylates and the corresponding weakly nucleophilic anilines under mild conditions by using p-trifluoromethylbenzoic anhydride and a catalytic amount of active titanium(IV) salt.

Various carboxylic esters are prepared in good to excellent yields by the reaction of equimolar amounts of silyl derivatives of carboxylic acids and alcohols by using a catalytic amount of active Lewis acid in hexamethyldisiloxane, a solvent.