Application of pig liver esterase catalyzed transesterification in organic media to the kinetic resolution of glycerol derivatives

The PLE/MPEG catalyzed transesterification of the glycerol ketals rac-1a and rac-1d–f with vinyl propionate in toluene proceeded with good selectivities (E=24–34) and gave the enantiomerically enriched S-alcohols 1a and 1d–f, and the S-esters 2a and 2d–f. High selectivities (E=99 and E≥200) were observed in the transesterification of the glycerol ether rac-3 and its desoxy analog rac-5, both having a secondary hydroxy group, with PLE/MPEG. In transesterifications in organic media PLE exhibited a much higher enantioselectivity than in hydrolysis in water.     

On the applicability of the Jones active site model of pig liver esterase to S-chiral and prochiral sulfinyl substrates

A series of racemic methyl sulfinylacetates was hydrolyzed in the presence of pig liver esterase (PLE) under kinetic resolution conditions to give the corresponding S-chiral sulfinylacetic acids and recovered esters in moderate enantiomeric purity. The Jones active site model was found to be suitable for explaining the enantioselectivity of the above reaction and for the PLE-mediated desymmetrization of prochiral sulfinyldicarboxylates.     

Dynamic kinetic resolution of transient hemiketals: a strategy for the desymmetrisation of prochiral oxetanols

Identification of an electron poor trifluoroacetophenone allows the formation of uniquely stable hemiketals from prochiral oxetanols. When exposed to a cobalt(ii) catalyst, efficient ring-opening to densely functionalized dioxolanes is observed. Mechanistic studies suggest an unprecedented redox process between the cobalt(ii) catalyst and the hemiketal that initiates the oxetane-opening. Based on this observation, a dynamic kinetic resolution of the transient hemiketals is explored that uses a Katsuki-type ligand for stereoinduction (up to 99 : 1 dr and 96 : 4 er) and allows a variety of 1,3-dioxolanes to be accessed (20 examples up to 98% yield).

Desymmetrization of prochiral oxetanols via an electron-deficient hemiketal intermediate is achieved. Key to this process is the catalyst''s chiral recognition of one of the two hemiketal enantiomers enabling an efficient dynamic kinetic resolution.     

Pig liver esterase (PLE)-mediated resolution of N-substituted 4-benzoyloxy-3-carbomethoxypiperidines: a convenient preparation of 4-hydroxy- and 4-benzoyloxy-3-carbomethoxypiperidines in enantiomerically pure form

Pig liver esterase (PLE) afforded smooth chemical resolution of racemic N-substituted 4-(benzoyloxy)-3-carbomethoxypiperidines. The enzyme showed good chemo- and enantioselective properties, thus allowing discrimination between the carbomethoxy and benzoate ester groups, the latter being more easily hydrolyzed. The proposed methodology also represents a practical means for the procurement of N-substituted 4-hydroxy-3-carbomethoxypiperidines in enantiomerically pure form.     

Organocatalytic kinetic resolution of racemic primary alcohols using a chiral 1,2-diamine derived from (S)-proline

A highly efficient and good enantioselective organocatalytic asymmetric acylation of racemic primary alcohols with acyl chlorides has been achieved catalyzed by a chiral 1,2-diamine derived from (S)-proline.     

(S)-selective kinetic resolution and chemoenzymatic dynamic kinetic resolution of secondary alcohols

(S)-Selective kinetic resolution was achieved through the use of a commercially available protease, which was activated with a combination of two different surfactants. The kinetic resolution (KR) process was optimized with respect to activation of the protease and to the acyl donor. The KR proved to be compatible with a range of functionalized sec-alcohols, giving good to high enantiomeric ratio values (up to >200). The enzymatic resolution was combined with a ruthenium-catalyzed racemization to give an (S)-selective dynamic kinetic resolution (DKR) of sec-alcohols. The DKR process works under very mild reaction conditions to give the corresponding esters in high yields and with excellent enantioselectivities.     

Rhodium(II)-catalyzed olefin cyclopropanation with the phenyliodonium ylide derived from Meldrum's acid

The phenyliodonium ylide 3a derived from Meldrum's acid reacts with olefins in the presence of Rh(II) carboxylate catalysts to afford cyclopropanes. The reaction is stereospecific. Enantioselectivities of up to 63% have been observed for the cyclopropanation of pent-1-ene. No 1,3-cycloadducts are formed between 3a and polarized olefins such as furan or 2,3-dihydrofuran.     

Trichosporon beigelli esterase (TBE): a versatile esterase for the resolution of economically important racemates

A hydrolase producing strain Trichosporon beigelli esterase (TBE) isolated from local cottage cheese in its native form has displayed versatility and high efficacy in the kinetic resolution of a wide range of economically important substrates, which include racemic secondary alcohols, such as 1-(6-methoxy-2-naphthyl)ethanol (E ∼ 316), 1-(3,4-methylenedioxyphenyl)ethanol and pentanol (E ∼ 180 and 156 resp.), and alkyl esters of carboxylic acids such as ibuprofen (E ∼ 340), 2-(benzylthio)propanoic acid (E ∼ 1000). In other substrates such as in the primary alcohol 2-(6-methoxy-2-naphthyl)propan-1-ol and carboxylic acids such as 2-(5-bromo-6-methoxy-2-naphthyl)propanoic acid, 2-(2-naphthyloxy)propanoic acid, and substituted 2-thiopropanoic acids, it displayed moderate to low selectivity. Commercial lipases such as CCL, PPL, and PSL were also used in the resolution of the substrates for comparative studies.     

Lipase-catalyzed kinetic resolution of (RS)-hydroxy tellurides

The enzymatic resolution of racemic mixtures of hydroxy tellurides with a range of lipases has been investigated. Lipase-B from Candida antarctica (CALB) gave the best conversions, providing both enantiomers with high enantiomeric purity. A comparative study of the effect of solvent and substrate on the enzymatic kinetic resolution was performed.     

Identification of a metagenome-derived esterase with high enantioselectivity in the kinetic resolution of arylaliphatic tertiary alcohols

35 metagenome-derived esterases bearing a GGG(A)X motif were screened for activity and enantioselectivity in the hydrolysis of a range of tertiary alcohol acetates. Most of the active esterases showed little or no enantioselectivity in the hydrolysis of the terpinyl acetate, linalyl acetate and 3-methylpent-1-yn-3-yl acetate. However, one esterase showed excellent enantioselectivity (E > 100) in the kinetic resolution of 1,1,1-trifluoro-2-phenylbut-3-yn-2-yl acetate as confirmed by a preparative scale reaction.     

Selective palladium(ii)-catalyzed acetoxylation of cyclododecene: a kinetic study

The acetoxylation of cyclododecene by palladium(II) acetate, hydroquinone and iron(II) phthalocyanine (FePc) was studied at 0.1 ÷ 1.0 MPa dioxygen pressure and temperature range of 313 to 335 K. Cyclododec-2-en-1-yl acetates in high selectivity (93.4%) at a conversion of cyclododecene up to 93.8% were obtained. The kinetic model assumed the significant inhibition effect of the allyl acetates. This revised version was published online in August 2006 with corrections to the Cover Date.     

An experimentally derived model for stereoselectivity in the aerobic oxidative kinetic resolution of secondary alcohols by (sparteine)PdCl2

A model for asymmetric induction in palladium-catalyzed aerobic oxidative kinetic resolution is described. The model is based on coordination complexes and general reactivity trends of the parent (sp)PdCl2 catalyst. The first example of a nonracemic chiral palladium alkoxide complex is presented, and exhibits the subtle steric influences of the C1 symmetric ligand sparteine.     

Chiral (acyclic diaminocarbene)gold(I)-catalyzed dynamic kinetic asymmetric transformation of propargyl esters

A highly enantioselective transformation catalyzed by chiral (acyclic diaminocarbene)gold(I) complexes is reported. The enantioselective synthesis of 2-substituted chromenyl pivalates from racemic phenol-substituted propargyl pivalates was developed. Rearrangement of the substrates in the presence of cationic gold gave allene intermediates, whose cyclization resulted in formation of enantioenriched product through a dynamic kinetic asymmetric transformation.     

Copper(I)-catalyzed addition of trifluoromethylated benzyl radicals derived from aryltrifluoroethyl bromides to terminal olefins

Relatively unreactive aryltrifluoroethyl bromides were reacted with 1-octene in the presence of CuCl and 2,2′-bipyridyl at high temperatures. Trifluoromethylated benzyl radical was generated, and a diastereomer mixture of radical adducts was obtained with a (60-70):(40-30) diastereomer ratio. Ph₃SnH reduction of the adducts gave the corresponding hydrocarbons with an isolated trifluoromethyl group. The reactions with styrene or aromatic and aliphatic silyl enol ethers led to the formation of trifluorodiphenylbutene and β-trifluoromethylated ketones, respectively.     

Novel dimethoxy(aminoalkoxy)borate derived from (S)-diphenylprolinol as highly efficient catalyst for the enantioselective boron-mediated reduction of prochiral ketones

The novel dimethoxyl(aminoalkoxy)borate 1 was isolated as a white crystalline dimer joined by H-bonding as evidenced by X-ray analysis, and demonstrated to be a highly effective catalyst for the asymmetric reduction of representative prochiral ketones with borane-DMS. Optically pure alcohols were obtained using only 1 mol % of catalyst 1 in up to 99% ee.     

Rh(i)-catalyzed stereoselective desymmetrization of prochiral cyclohexadienones via highly exo-selective Huisgen-type [3 + 2] cycloaddition

A Rh(i)-catalyzed highly stereoselective desymmetrization of 2-alkynylbenzaldehyde-tethered cyclohexadienones triggered by intramolecular Huisgen-type [3 + 2] cycloaddition has been developed. This method enables convergent construction of complex epoxy-bridged polycyclic ring systems with five contiguous stereocenters with excellent exo-selectivity and broad substrate scope. The highly atom-economical process involves 6-endo-dig cyclization of carbonyl oxygen onto an activated alkyne resulting in a highly reactive metal–benzopyrylium intermediate, which readily undergoes intramolecular [3 + 2] annulation/hydration. Asymmetric induction is also achieved for the first time in Rh(i)-catalyzed 1,3-dipolar cycloaddition using an easily accessible chiral diene as the ligand.

A Rh(i)-catalyzed highly stereoselective desymmetrization of 2-alkynylbenzaldehyde-tethered cyclohexadienones triggered by intramolecular Huisgen-type [3 + 2] cycloaddition has been developed.     

Ru(III)-catalyzed oxidation of pyruvic acid by iodate -A kinetic study

Ru(III) acts as a catalyst in the oxidative decarboxylation of pyruvic acid by iodate. The reaction is found to be first order with respect to [oxidant] and [catalyst] and fractional order in [pyruvic acid]. Increase in the concentration of H₂SO₄ and decrease in the dielectric constant of the medium retard the oxidation process. The product of oxidation is acetic acid. A mechanism involving the formation of a complex between the substrate and the catalyst, which reacts with the oxidant in the slow step is proposed. The formation constant of the complex and the rate constant of the slow step are determined. This revised version was published online in June 2006 with corrections to the Cover Date.