Investigations into the parallel kinetic resolution of 2-phenylpropanoyl chloride using quasi-enantiomeric oxazolidinones

The resolution of 2-phenylpropanoyl chloride using an equimolar combination of quasi-enantiomeric oxazolidinones is discussed. The levels of diastereoselectivity were found to be dependent upon the structural nature of the metallated oxazolidinone, temperature and metal counter-ion.     

A reactivity/affinity switch for parallel kinetic resolution: alpha-amino acid quasienantiomers and the resolution of cyclopropene carboxylic acids

A new type of parallel kinetic resolution (PKR) is reported in which quasienantiomers with very similar reactivities give products whose chromatographic properties diverge upon the addition of fluoride. This concept of a reactivity/affinity switch is applied to the PKR of cyclopropene carboxylic acids with all-carbon quaternary centers. This is the first application of alpha-amino acid quasienantiomers in PKR, and it is a complementary approach for acyltransfer systems where the asymmetry is induced by the nucleophile rather than the leaving group. Excellent diastereoselectivities (ranging from 90:10 to 99.5:5) and good yields were obtained for both quasienantiomeric products, and the reactions can be run on significant scale because the separation is trivial. High-level DFT calculations (B3LYP functional with the 6-31+G(d,p) basis set) provided transition-state structures with relative energies that are in accord with the experimental observations.     

Enzymatic kinetic resolution of tropic acid

A new strategy has been developed for the CAL-B catalysed kinetic resolution of tropic acid by which both enantiomers of tropic acid can be obtained in good enantiomeric excess. (R)-Tropic acid was synthesised with 90% ee and (S)-tropic acid butyl ester in 99% ee by the hydrolysis of tropic acid butyl ester. The other enantiomers were available through the enzymatically catalysed reaction of tropic acid lactone with butanol to give (S)-tropic acid lactone and (R)-tropic acid ester in >98% ee.     

Enzymatic resolution of substituted mandelic acids

A series of substituted mandelic acids were prepared and subjected to enzymatic resolution utilizing Lipase PS ‘Amano’.     

Dynamic kinetic resolution of alpha-hydroxy acid esters

[formula: see text] Enzymatic resolution in combination with ruthenium-catalyzed racemization of the substrate led to dynamic kinetic resolution of alpha-hydroxy esters in good yields and excellent ee's. Studies of different parameters showed that the best results were obtained using Pseudomonas cepacia lipase, ruthenium catalyst 3, and 4-chlorophenyl acetate as acyl donor in cyclohexane.     

Organocatalytic conversion of arylglyoxals into optically active mandelic acid derivatives

A novel protocol for the organocatalytic conversion of arylglyoxals into the corresponding α-hydroxy arylacetic acid methyl esters has been developed. The catalyst consists of a combination of a commercially available cinchona alkaloid derivative and an achiral thiol and leads to enantiomerically enriched products (ee_max 83%) under mild reaction conditions. The alkaloid can be easily recovered and reused without loss in activity and selectivity.     

Probing the parallel kinetic resolution of 1-phenylethanol using quasi-enantiomeric oxazolidinone adducts

The parallel kinetic resolution of racemic 1-phenylethanol using an equimolar combination of quasi-enantiomeric oxazolidinones is discussed. The levels of diastereoselectivity were high leading to separable quasi-enantiomeric esters in good yield.     

Optical resolution of mandelic acid derivatives by column chromatography on crosslinked cyclodextrin gels

Crosslinked α- and β-cyclodextrin gels (α-CD-E and β-CD-E) were used for the chromatographic resolution of racemic mandelic acid and its derivatives. β-CD-E bound L -(+)-isomers preferentially over D -(?)-isomers and resolved DL -methyl mandelate to give a D -(?)-isomer of 100% optical purity in the first fraction. Mandelic acid, ethyl mandelate, and O-methylated mandelic acid yielded resolutions of 65–83% in initial fractions. α-CD-E, on the contrary, bound D -(?)-isomers more strongly than L -(+)-isomers, resolving DL -methyl mandelate to a smaller extent than β-CD-E. Binding of DL -mandelic acid and DL -methyl mandelate on β-CD-E was studied quantitatively by the equilibrium method. β-CD-E has a similar binding capacity to starch with 1:1 stoichiometry but bound much more strongly than starch. β-CD-E has the same mode of selectivity as starch for the asymmetric binding of the mandelic acid derivatives, but α-CD-E has a reverse selectivity to β-CD-E and starch.     

Quasienantiomeric levoglucosenone and isolevoglucosenone allow the parallel kinetic resolution of a racemic nitrone

Cycloadditions of chiral pyrroline N-oxides to levoglucosenone (1) and isolevoglucosenone (2) proceed with a high level of double asymmetric induction. Partial kinetic resolutions (KR) of both enantiomers of a racemic nitrone 3 were achieved, and a parallel kinetic resolution (PKR) experiment allowed the stereoselective divergent synthesis of two quasienantiomeric imino-C-disaccharide precursors.     

Lipase-catalyzed kinetic and dynamic kinetic resolution of 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid

A dynamic kinetic resolution method for the preparation of enantiopure 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (R)-2 was developed involving the CAL-B-catalyzed enantioselective hydrolysis of the corresponding ethyl ester (±)-1 in toluene/acetonitrile (4:1) containing 1 equiv of added water and 0.25 equiv of dipropylamine. This method allowed the preparation of (R)-2 (ee = 96%) with 80% isolated yield. The kinetic resolution of (±)-1 in diisopropyl ether at 3 °C afforded both enantiomers with ee ⩾92%.     

Investigations into the nitric acid mediated dehalonitration of halophenols

A reaction of nitric acid with bromophenols and iodophenols results in substitution of the halogen with a nitro group. The study indicates moderate reactivity for bromophenols and iodophenols, while chlorophenols were found to be sluggish in this reaction.     

Investigation of the cyclodextrin complexes of mandelic acid derivatives

Racemic free mandelic acid and its methyl, ethyl, isoamyl and benzyl esters were found to form inclusion complexes with all the three studied natural cyclodextrins proved by thermoanalytical results. Differences between the solid state stability of guests were detected mainly by evolved gas analysis. Even signs of an eventual optical resolution by molecular inclusion were observed in several cases, but still not sufficiently proven. Due to the rather high volatility and low melting points of the majority of guest substances DSC technique was found to be suitable for studying the cyclodextrin complexes of mandelic acid. Dedicated to Prof. József Szejtli on the occasion of his 60^th birthday     

Asymmetric synthesis of silylated alpha-amino acid esters through dynamic kinetic resolution

Esters of three types of silylated alpha-amino acids have been prepared from appropriate zirconaaziridines. Slow addition (syringe pump) of the (R,R) carbonate of trans-stilbene gave metallacycles with the maximum possible diastereomeric excess (as determined by the diastereomeric excess produced by the Hoffmann test-the same reaction but with racemic carbonate). Methanolysis gave esters (RO(2)C)CH(R')(NHPh) (R' = Me(3)Si, Me(3)SiCH(2), and p-Me(3)SiC(6)H(4)) with the same optical purity at the alpha carbon.     

Molecular mechanism of DCR phenomenon observed in (RS)-1-cyclohexylethylamine–mandelic acid resolution system

In the resolution system of (RS)-1-cyclohexylethylamine (CHEA) with (S)-mandelic acid (MA), the DCR (dielectrically controlled resolution) phenomenon was clearly observed. (S)-CHEA and (R)-CHEA were obtained as less-soluble salts from 2-propanol (ε = 18) and water (ε = 78), respectively. Although (S)-MAs pack similarly in the crystals of both of the salts, the chiral spaces formed between the columns of (S)-MAs are significantly different in shape. The present study showed that these chiral spaces are crucial to molecular recognition and their shapes are greatly influenced by the dielectric property of the solvent employed.     

Dynamic parallel kinetic resolution of α-ferrocenyl cation initiated by chiral Brønsted acid catalyst

The dynamic parallel kinetic resolution (DPKR) of an α-ferrocenyl cation intermediate under the influence of a chiral conjugate base of a chiral phosphoric acid catalyst has been demonstrated in an S_N1 type substitution reaction of a racemic ferrocenyl derivative with a nitrogen nucleophile. The present method provides efficient access to a ferrocenylethylamine derivative in a highly enantioselective manner, which is potentially useful as a key precursor of chiral ligands for metal catalysis. The mechanism of the present intriguing resolution system was elucidated by control experiments using the enantio-pure precursor of relevant α-ferrocenyl cation intermediates and the hydroamination of vinylferrocene. Further theoretical studies enabled the elucidation of the origin of the stereochemical outcome as well as the efficient DPKR. The present DPKR, which opens a new frontier for kinetic resolution, involves the racemization process through the formation of vinylferrocene and the chemo-divergent parallel kinetic resolution of the enantiomeric α-ferrocenyl cations generated by the protonation/deprotonation sequence of vinylferrocene.

The dynamic parallel kinetic resolution (DPKR) of an enantiomeric α-ferrocenyl cation using a chiral phosphate anion of an acid catalyst was accomplished by the combination of the PKR and the racemization through the formation of vinylferrocene.     

Dynamic kinetic resolution of racemic tropic acid ethyl ester and its derivatives

The dynamic kinetic resolution of racemic mixtures of tropic acid ethyl ester under substrate racemizing conditions was studied using lipase PS with a ruthenium catalyst. Isopropenyl acetate was used as an acyl donor, since it was found to be compatible with both catalysts; this resulted in an efficient dynamic kinetic resolution. With this process, a variety of racemic tropic acid ethyl esters were transformed to optically active acetoxy-2-arylpropionic acid ethyl esters with 60-88% yields and 53-92% ee.     

动力学拆分法的研究进展

综述了光活性化合物动力学拆分法的研究进展及其在不对称合成中的应用。     

Kinetic resolution and parallel kinetic resolution of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates for the asymmetric synthesis of 5-alkyl-cispentacin derivatives

Conjugate addition of lithium dibenzylamide to methyl 5-isopropyl, 5-phenyl- and 5-tert-butyl-cyclopentene-1-carboxylates occurs with high levels of substrate control (>88% de), with preferential addition to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the stereodirecting 5-alkyl substituent. Treatment of a range of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates with both lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide and lithium (+/-)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide indicates significant enantiorecognition in their mutual kinetic resolutions, with preferential addition anti- to the 5-alkyl substituent, giving the 1,2-syn-1,5-anti-arrangement (E >16) after enolate protonation anti- to the amino functionality. The kinetic resolution of a range of methyl (+/-)-5-alkyl-cyclopentene-1-carboxylates with lithium (S)-N-benzyl-N-alpha-methylbenzylamide, and their efficient parallel kinetic resolution with a pseudoenantiomeric mixture of lithium (S)-N-benzyl-N-alpha-methylbenzylamide and lithium (R)-N-3,4-dimethoxybenzyl-N-alpha-methylbenzylamide are also demonstrated, giving a range of 5-alkyl-cispentacin derivatives in >98% de and high ee after N-deprotection.