Optically active imidazole-containing polymers

In order to investigate the stereospecificity of enzyme-catalyzed reactions, an optically active copolymer of 4(5)-vinylimidazole and 2,5(S)-dimethyl-1-hepten-3-one was synthesized, and its effects on the solvolytic rates, in ethanol-water, of the p-nitrophenyl and 4-carboxy-2-nitrophenyl esters of 3(R)- and 3(S)-methylpentanoic acid and of the commercially available N-carbobenzoxy-(R)- and (S)-phenylalanine p-nitrophenyl esters were investigated. The optically active comonomer was prepared by thermal decomposition of solid (+)-1-piperidino-2,5(S)-dimethylheptan-3-one hydrochloride, which was obtained from the reaction of 2(S)-methylbutyllithium with 3-piperidino-2-methylpropionitrile. The 3(R)-methylpentanoic acid was prepared in 92% optical purity from L -alloisoleucine via diazotization in concentrated hydrobromic acid and subsequent reductive debromination with zinc amalgam in dilute hydrochloric acid. In the optically active copolymer-catalyzed solvolyses of the optically active esters performed at pH values of 6–8 no significant differences between the solvolytic rates of (R) and (S) isomers of substrates were observed. Poly-L -histidine was also employed as a catalyst for the solvolyses of these substrates. At pH 6.0 in ethanol–water the latter catalyst also failed to exhibit specificity towards (R) and (S) substrates.     

Gold(I)/Chiral N,N′‐Dioxide–Nickel(II) Relay Catalysis for Asymmetric Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement

A highly efficient asymmetric cascade reaction between alkynyl esters and allylic alcohols has been realized. Key to success was the combination of a hydroalkoxylation reaction catalyzed by a π‐acidic gold(I) complex with a Claisen rearrangement catalyzed by a chiral Lewis acidic N,N′‐dioxide–nickel(II) complex. A range of acyclic α‐allyl β‐keto esters were synthesized in high yields (up to 99 %) with good diastereoselectivities (up to 97:3) and excellent enantioselectivities (up to 99 % ee ) under mild reaction conditions. These products can be easily transformed into optically active β‐hydroxy esters, β‐hydroxy acids, or 1,3‐diols.     

Gold(I)/Chiral N,N′-Dioxide–Nickel(II) Relay Catalysis for Asymmetric Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement

A highly efficient asymmetric cascade reaction between alkynyl esters and allylic alcohols has been realized. Key to success was the combination of a hydroalkoxylation reaction catalyzed by a π-acidic gold(I) complex with a Claisen rearrangement catalyzed by a chiral Lewis acidic N,N′-dioxide–nickel(II) complex. A range of acyclic α-allyl β-keto esters were synthesized in high yields (up to 99 %) with good diastereoselectivities (up to 97:3) and excellent enantioselectivities (up to 99 % ee) under mild reaction conditions. These products can be easily transformed into optically active β-hydroxy esters, β-hydroxy acids, or 1,3-diols.     

Kinetic Resolution of Racemic Secondary Benzylic Alcohols by the Enantioselective Esterification Using Pyridine‐3‐carboxylic Anhydride (3‐PCA) with Chiral Acyl‐Transfer Catalysts

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.     

Solvolysis of 4-acyloxy-3-nitrobenzoic acid substrates catalyzed by polyethylenimine derivatives

The solvolytic reactions of anionic activated esters (S_n^?) catalyzed by dodecane-block-poly[ethylenimine-graft-4(5)-methylimidazole] and related model compounds were investigated. Hydrolysis of 4-acetyl-3-nitrobenzoic acid (S₂^?) as a function of pH suggested that electrostatic interactions are operative only in the higher molecular weight polymers. Apolar interactions were evident from the greater catalytic rates observed for the hydrolysis of a series of 4-acetoxy-3-nitrobenzoic acid substrates (S_n^?). The largest rate enhancements were reflected by catalysts that make effective use of the electrostatic interaction and also provide an apolar binding site. Dodecane-block-poly[ethylenimine-graft-4(5)-methylimidazole], with a DP = 85, catalyzed hydrolysis of S_n^?(n = 2, 4, and 7), in excess substrate, exhibited saturation kinetics and followed a simple Michaelis-Menten-type mechanism. Inhibition of the catalyst in the hydrolysis of S₁₂^? was observed and can be rationalized by analogy to certain multisite enzymatic reactions.     

Polymeric stationary phase,based on (R,R)‐tartramide and bisphenol S,with potential chiral properties

A new polymeric stationary phase with potential chiral properties, obtained by the chemical modification of the parent copolymer of dimethacrylate esters of bisphenol S and divinylbenzene, is presented. Hydroxyl functional groups present in the copolymer chemical structure are blocked by optically active selectors of (R,R)‐tartramide derivatives. The influence of the chemical modification of the parent copolymer on its porous structure has been studied. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2566–2574, 2004     

Acid-labile δ-ketal-β-hydroxy esters by asymmetric hydrogenation of corresponding δ-ketal-β-keto esters in the presence of CaCO3

A series of acid-labile, optically pure ε-substituted δ-ketal-β-hydroxy esters were obtained by a Ru-SunPhos catalyzed asymmetric hydrogenation of the corresponding ε-substituted δ-ketal-β-keto esters. CaCO(3) played a dual role in the hydrogenation reaction--removing the acid generated during the formation of the catalyst and maintaining the activity of the catalyst.     

A Mild and Efficient Alumina-Promoted Synthesis of t-Butyl Esters

A wide variety of aliphatic acid chlorides including an optically active one has been efficiently converted to their t-butyl esters under very mild reaction conditions by employing activated alumina as a catalyst.     

Direct catalytic asymmetric mannich reactions of malonates and beta-keto esters

The first catalytic asymmetric direct Mannich reaction of malonates and beta-keto esters has been developed. Malonates react with an activated N-tosyl-alpha-imino ester catalyzed by chiral tert-butyl-bisoxazoline/Cu(OTf)(2) to give the Mannich adducts in high yields and with up to 96% ee. These reactions create a chiral quaternary carbon center and it is demonstrated that this new direct Mannich reactions provides for example a new synthetic procedure for the formation of optically active beta-carboxylic ester alpha-amino acid derivatives. A series of different beta-keto esters with various ester substituents has been screened as substrates for the catalytic asymmetric direct Mannich reaction and it was found that the best results in terms of yield, diastereo- and enantioselectivity were obtained when tert-butyl esters of beta-keto esters were used as the substrate. The reaction of different beta-keto tert-butyl esters with the N-tosyl-alpha-imino ester gave the Mannich adducts in high yields, diastereo- and enantioselectivities (up to 95% ee) in the presence of chiral tert-butyl-bisoxazoline/Cu(OTf)(2) as the catalyst. To expand the synthetic utility of this direct Mannich reaction a diastereoselective decarboxylation reaction was developed for the Mannich adducts leading to a new synthetic approach to attractive optically active beta-keto alpha-amino acid derivatives. Based on the stereochemical outcome of the reactions, various approaches of the N-tosyl-alpha-imino ester to the chiral bisoxazoline/Cu(II)-substrate intermediate are discussed.     

Desilylation‐Activated Propargylic Transformation: Enantioselective Copper‐Catalyzed [3+2] Cycloaddition of Propargylic Esters with β‐Naphthol or Phenol Derivatives

A copper‐catalyzed asymmetric [3+2] cycloaddition of 3‐trimethylsilylpropargylic esters with either β‐naphthols or electron‐rich phenols has been realized and proceeds by a desilylation‐activated process. Under the catalysis of Cu(OAc)₂?H₂O in combination with a structurally optimized ketimine P,N,N‐ligand, a wide range of optically active 1,2‐dihydronaphtho[2,1‐b]furans or 2,3‐dihydrobenzofurans were obtained in good yields and with high enantioselectivities (up to 96 % ee). This represents the first desilylation‐activated catalytic asymmetric propargylic transformation.     

Naphthopyranquinone Antibiotics: Novel enantioselective syntheses of frenolicin B and some of its stereoisomers

Two new enantioselective syntheses of the naphthopyranquinone antibiotic frenolicin B ( 1 ), of its enantiomer 2 , and of its diastereoisomers 3 and 4 were accomplished using two different routes from optically active β-Hydroxy esters (R)- and (S)- 11 and 18. β-Hydroxy esters (R)- and (S)- 11 were prepared stereoselectively from optically active sulfenylacetates (S)- and (R)- 10 , respectively (Scheme 2, Method A). Alternatively, compound 18 was obtained in excellent yield by enantioselective hydrogenation of the corresponding β-keto ester 17 , using a chiral ruthenium-complex catalyst (Scheme 3, Method B). Subsequently, compounds (S)- 11 and 18 were transformed into frenolicin B (1). In analogy, Stereoisomers 2–4 were prepared from (S)- and (R)- 11 in good yields.     

A study of the kinetics and mechanism of amidation of 4-nitrobenzoic acid with ammonia,catalyzed by boric acid in the presence of polyethylene glycol PEG-400

Kinetics of the reaction of 4-nitrobenzoic acid with ammonia, catalyzed by the system constituted by boric acid and PEG-400 poly(ethylene glycol), was studied. A catalysis mechanism was suggested, which consists in original synthesis of incomplete polyethylene glycol borate esters, formation on their basis of 4-nitrobenzoic acid borate esters, and their further amidation with ammonia.     

Preparation and photochemical study of soluble optically active block copolymethacrylates and azo-containing random copolymethacrylates

A series of soluble optically active block copolymers of trityl methacrylate (TrMA) and cyclohexyldiphenylmethyl methacrylate (CHDPMA) with methyl methacrylate (MMA) and n-butyl methacrylate (n-BuMA) were synthesized using the complex of 9-fluorenyllithium and (S,S)-(+)-2,3-dimethoxy-1,4-bis(dimethylamino)butane as an initiator in toluene at −78°C. Soluble optically active random copolymers derived from TrMA and azo methacrylates, 6-(4-phenylazophenoxy)hexyl methacrylate (PAHM) and 2-(4-phenylazophenoxy)ethyl methacrylate (PAEM), were obtained under similar anionic polymerization conditions. Optical activities of the copolymers largely depended on the weight percentage of TrMA or CHDPMA component in the polymer chains. Solubility and film formability were significantly improved for the copolymers. Irradiation of optically active TrMA–MMA and CHDPMA–MMA block copolymer films containing photoacid, diphenyl-p-tolylsulfonium triflate, causes the partial hydrolysis of bulky esters and results in the conformational randomization of helical chains, which in turn leads to a significant change in optical rotation of the films. Photoisomerization studies of azo-containing random copolymers indicate that the trans to cis isomerization induces the helical conformation racemization in solution. © 1997 John Wiley & Sons, Inc.     

The first asymmetric esterification of free carboxylic acids with racemic alcohols using benzoic anhydrides and tetramisole derivatives: an application to the kinetic resolution of secondary benzylic alcohols

A variety of optically active carboxylic esters are produced by the kinetic resolution of racemic secondary benzylic alcohols using free carboxylic acids with benzoic anhydride and tetramisole derivatives. 4-Methoxybenzoic anhydride (PMBA) is the best reagent to use in producing the corresponding esters in high ee when the reaction is catalyzed by (+)-benzotetramisole (BTM); by contrast, when non-substituted benzoic anhydride is used as a coupling reagent, the resulting optically active alcohols are obtained with high selectivities. This protocol directly produces chiral carboxylic esters from free carboxylic acids and racemic secondary alcohols by utilizing the trans-acylation process to generate mixed anhydrides from acid components and benzoic anhydride derivatives under the influence of chiral catalysts.     

Synthesis and polymerization of optically active L-[α-(N-p-acryloxybenzoyl)alanine ethyl esters]

New optically active monomers L -[α-(N-p-acryloxybenzoyl)alanine ethyl esters] (I) and their polymers were synthesized. The title monomers (I) were prepared by the reaction of 1-p-acryloxybenzoyloxy-4-chlorobenzotriazoles (II) with L -alanine ethyl ester hydrochloride, by aminolysis of the active monoester. The new typical active ester (II) was synthesized by the N-hydroxy compound active-ester methods in excellent yield. Before the synthesis of the optically active monomers was carried out, a model study of the aminolysis of the two active esters was performed.     

Organocatalytic asymmetric direct alpha-alkynylation of cyclic beta-ketoesters

The first organocatalytic enantioselective direct alpha-alkynylation of beta-ketoesters and 3-acyl oxindoles is described. It is demonstrated that activated beta-halo-alkynes undergo nucleophilic acetylenic substitution catalyzed by chiral phase-transfer compounds to afford the alkynylated products in high yields and excellent enantioselectivities. The potential of the reaction is first demonstrated for various alkynylating reagents having chloride and bromide as the leaving groups and substituents such as allyl and alkyl esters, amides, ketones, and sulfones. These reactions proceed with 74-99% yield and 88-97% ee. Then the scope in nucleophile is demonstrated for a large number of cyclic beta-ketoesters with various ring-sizes and for oxindoles as well. The corresponding optically active products are formed in high yields and with enantioselectivities up to 98% ee. The procedure allows for the stereocontrolled attachment of an ethynyl unit in the alpha-position to the carbonyl compound by facile removal of the activating group, and this has been demonstrated for a number of the optically active allyl esters. Furthermore, the synthesis of optically active 1,4-enynes is also shown. The isolation and characterization by X-ray analysis of the catalyst with p-nitrophenolate as the counterion allowed us to propose a model of the catalyst-substrate intermediate which might account for the observed enantioselectivity of the organocatalytic enantioselective alpha-alkynylation reaction. Furthermore, it is suggested that this intermediate is also the reactive species for a number of other electrophiles adding to beta-ketoesters giving enantioselectivities in the range of 90-98% ee.     

The Control of the Stereochemistry in the Palladium‐Catalyzed Alternating Styrene/Carbon Monoxide Copolymerization: Effect of the Chirality of the Ligand and of the Ligand‐to‐Palladium Ratio,Preliminary Communication

Diaquapalladium(2+) trifluoromethanesulfonates modified with (4R,4′S)‐ or (4S,4′S)‐2,2′‐bis(4‐benzyl‐4,5‐dihydrooxazole) (C_s‐ and C₂‐ligands) produce isotactic poly(1‐oxo‐2‐phenylpropane‐1,3‐diyl) through copolymerization of styrene with carbon monoxide. However, the same meso‐catalyst in the presence of the free ligand leads to prevailingly syndiotactic growth of the copolymer, whereas the optically active catalyst, when used in the presence of the free enantiomeric ligand, gives an atactic copolymer.     

Hydrophobic interactions in the enantioselective solvolyses of optically active activated esters by imidazole-containing polymeric surfactants

Enantioselective solvolyses of optically active activated esters in the aggregate system of optically active polymeric surfactants containing imidazole and benzene moieties were performed. The catalyst polymers [copoly(MHis-DEVAB)] employed were copolymers of N-methacryloyl-L -histidine methyl ester (MHis) with N,N-dimethyl-N-hexadecyl-N-[10-(p-vinylcarboxanilido) decyl]ammonium bromide(DEVAB). In the solvolyses of N-carbobenzoxy-D - and L -phenylalanine p-nitrophenyl esters (D -NBP and L -NBP) by polymeric catalysts, copoly(MHis-DEVAB) exhibited not only increased catalytic activity but also enhanced enantioselectivity as the mole percent of surfactant monomers in the copolymers increased. The polymeric catalysts showed noticeable enantioselective solvolyses toward D - and L -NBP of the substrates employed. As the reaction temperature was lowered for the solvolyses of D - and L -NBP with the catalyst polymer containing 4.8 mol% of MHis, an increased reaction rate and enhanced enantioselectivity were observed. The coaggregate systems of the polymer and monomeric surfactants were also investigated. The case of a coaggregate system consisting of 70 mol% of cetyldimethylethylammonium bromide with polymeric catalyst showed maximum enantioselective catalysis, viz., k_cat (L )/k_cat(D ) = 6.68. The catalyst polymers in the sonicated solvolytic solutions were confirmed to form large ordered aggregate structure by electron microscopic observation. From these results, it is concluded that hydrophobic interaction in ordered aggregate structure plays an important role in enantioselective catalysis of optically active imidazole-containing polymers.     

Propylene polymerizations with a binary metallocene system—Chain shuttling caused by trimethylaluminium between active catalyst centers

Propylene was polymerized at varying trimethylaluminium (TMA) concentration with a homogeneous binary metallocene catalyst system activated by methylaluminoxane (MAO) in an attempt to better understand interactions between active catalyst sites and to clarify the role of the TMA as a chain shuttling agent. TMA‐free polymerization conditions were obtained by chemical treatment of MAO solution with 2,6‐di‐tert‐butyl‐4‐methylphenol (BHT). A binary catalyst system consisting of catalyst precursors diphenylmethyl(cyclopentadienyl)(9‐fluorenyl)zirconium dichloride ( 1 ) producing high M_w syndiotactic polypropylene and rac‐dimethylsilylbis(4‐tert‐butyl‐2‐methyl‐cyclopentadienyl)zirconium dichloride ( 2 ) producing low M_w isotactic polypropylene was investigated. At the studied polymerization conditions, chain shuttling between the active catalysts caused by TMA was confirmed. The chain shuttling reactions caused changes in catalyst activity, molecular weights, melting behavior, and polymer microstructure. We propose that TMA is capable to transfer a growing polymer chain from catalyst 2 to catalyst 1 , and a stereoblock copolymer is formed. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1364–1376, 2007     

A N,N′‐Dioxide–Copper(II) Complex as an Efficient Catalyst for the Enantioselective and Diastereoselective Mannich‐Type Reaction of Glycine Schiff Bases with Aldimines

Mild mannered! A highly diastereo‐ and enantioselective Mannich‐type reaction of glycine Schiff base 1 has been developed by using the N,N′‐dioxide L ‐Cu^II complex as a catalyst. Various optically active anti‐α,β‐diamino acid esters were obtained in good yields with up to 96:4 d.r. and 97 % ee. This straightforward method features a low catalyst loading and mild reaction conditions.