Kinetic Resolution Of Tertiary Alcohols Research Articles

Anion effect on enantioselective oxidative NHC catalysis: highly efficient kinetic resolution of tertiary alcohols and beyond

The effect of the counter-anion in the azolium pre-catalyst on enantio-control in oxidative NHC catalysis is demonstrated systematically for the first time in acylative kinetic resolution of oxindole-derived tertiary alcohols.

Kinetic Resolution of Tertiary Alcohols by Chiral Organotin-Catalyzed O-Acylation.

A novel highly enantioselective method for the kinetic resolution of racemic tertiary alcohols has been achieved through chiral organotin-catalyzed intermolecular acylation of the hydroxyl group. This process has demonstrated a broad substrate scope (both alkyl- and aryl-substituted tertiary alcohols) with high enantioselectivity under mild reaction conditions, affording the corresponding products and the recovered tertiary alcohols with high enantioselectivities, with s factors up to >200.

Recent Advances in Catalytic Nonenzymatic Kinetic Resolution of Tertiary Alcohols

AbstractThe kinetic resolution (KR) of racemates is one of the most widely used approaches to access enantiomerically pure compounds. Over the past two decades, catalytic nonenzymatic KR has gained popularity in the field of asymmetric synthesis due to the rapid development of chiral catalysts and ligands in asymmetric catalysis. Chiral tertiary alcohols are prevalent in a variety of natural products, pharmaceuticals, and biologically active chiral compounds. The catalytic nonenzymatic KR of racemic tertiary alcohols is a straightforward strategy to access enantioenriched tertiary alcohols. This short review describes recent advances in catalytic nonenzymatic KR of tertiary alcohols, including organocatalysis and metal catalysis.1 Introduction2 Organocatalysis2.1 Peptide Catalyst2.2 Chiral Phosphoric Acid Catalyst2.3 Chiral Lewis Base Catalyst2.4 Chiral Quaternary Ammonium Salt Catalyst3 Metal Catalysis3.1 Mixed La-Li Heterobimetallic Catalyst3.2 Rh Catalyst3.3 Hf Catalyst3.4 Pd Catalyst3.5 Cu Catalyst3.6 Ag Catalyst4 Conclusion and Outlook

ArPNO-catalyzed acylative kinetic resolution of tertiary alcohols: access to 3-hydroxy-3-substituted oxindoles.

Bifunctional chiral 4-aryl-pyridine-N-oxides (ArPNO) were reported for the acylative kinetic resolution of 3-hydroxy-3-substituted oxindoles, where the oxygen acts as the nucleophilic site. Using less sterically hindered acetic anhydride, both the recovered tertiary heterocyclic alcohols and the ester products exhibited good to excellent results with s-factors up to 167. Control experiments supported the dual activation manner, where the N-oxide group and N-H proton in ArPNO were crucial for high selectivity and enhanced catalytic reactivity. Compared with the extensively used chiral NHC, isochalcogenourea, and DMAP catalysts, we found that chiral ArPNO were also efficient organocatalysts in the kinetic resolution of tertiary alcohols.

Recent Advances in Kinetic Resolution of Tertiary Alcohols

Recent Advances in Kinetic Resolution of Tertiary Alcohols

Asymmetric Enamide-Imine Tautomerism in the Kinetic Resolution of Tertiary Alcohols.

An efficient protocol for kinetic resolution of tertiary alcohols has been developed through an unprecedented asymmetric enamide-imine tautomerism process enabled by chiral phosphoric acid catalysis. A broad range of racemic 2-arylsulfonamido tertiary allyl alcohols could be kinetically resolved with excellent kinetic resolution performances (with s-factor up to >200). This method is particularly effective for a series of 1,1-dialkyl substituted allyl alcohols, which produced chiral tertiary alcohols that would be difficult to access via other asymmetric methods. Facile and versatile transformations of the chiral α-hydroxy imine and enamide products, especially the efficient stereodivergent synthesis of all four stereoisomers of β-amino tertiary alcohols using one enantiomer of the catalyst, demonstrated the value of this kinetic resolution method.

Asymmetric Enamide–Imine Tautomerism in the Kinetic Resolution of Tertiary Alcohols

AbstractAn efficient protocol for kinetic resolution of tertiary alcohols has been developed through an unprecedented asymmetric enamide‐imine tautomerism process enabled by chiral phosphoric acid catalysis. A broad range of racemic 2‐arylsulfonamido tertiary allyl alcohols could be kinetically resolved with excellent kinetic resolution performances (with s‐factor up to >200). This method is particularly effective for a series of 1,1‐dialkyl substituted allyl alcohols, which produced chiral tertiary alcohols that would be difficult to access via other asymmetric methods. Facile and versatile transformations of the chiral α‐hydroxy imine and enamide products, especially the efficient stereodivergent synthesis of all four stereoisomers of β‐amino tertiary alcohols using one enantiomer of the catalyst, demonstrated the value of this kinetic resolution method.

Kinetic Resolution of Tertiary Alcohols by Chiral DMAP Derivatives: Enantioselective Access to 3-Hydroxy-3-substituted 2-Oxindoles.

We developed an efficient acylative kinetic resolution of 3-hydroxy-3-substituted 2-oxindoles by a chiral DMAP derivative having a 1,1'-binaphthyl with two tert-alcohols units. A wide range of 3-hydroxy-3-substituted oxindoles having various functional groups were efficiently resolved (14 examples, up to s = 60) in the presence of 1 mol % of catalyst within 3-9 h. Multigram-scale reactions (10 g) also proceeded with a high s-factor (s = 43) within 5 h.

NHC-Catalyzed Kinetic Resolution of Tertiary Alcohols

NHC-Catalyzed Kinetic Resolution of Tertiary Alcohols

Special Rhodococcus sp. CR-53 esterase Est4 contains a GGG(A)X-oxyanion hole conferring activity for the kinetic resolution of tertiary alcohols

Rhodococci are highly adaptable bacteria, capable to degrade or transform a large number of organic compounds, including recalcitrant or toxic products. However, little information is available on the lipases of the genus Rhodococcus, except for LipR, the first lipase isolated and described from strain Rhodococcus CR-53. Taking into consideration the interest raised by the enzymes produced by actinomycetes, a search for new putative lipases was performed in strain Rhodococcus CR-53. We describe here the isolation, cloning, and characterization of intracellular esterase Est4, a mesophilic enzyme showing preference for short-chain-length acyl groups, without interfacial activation. Est4 displays moderate thermal and pH stability and low tolerance to most tested ions, being inhibited by detergents like sodium dodecyl sulfate and Triton X-100®. Nevertheless, the enzyme shows good long-term stability when stored at 4-20°C and neutral pH. Amino acid sequence analysis of Est4 revealed a protein of 313 amino acids without a signal peptide, bearing most of the conserved blocks that define bacterial lipase family IV, thus being assigned to this family. Detection of a GGG(A)X oxyanion hole in the enzyme motivated the evaluation of Est4 ability to convert tertiary alcohol esters. The newly discovered esterase Est4 from Rhodococcus CR-53 successfully hydrolyzed the tertiary alcohol esters linalyl acetate, terpinyl acetate, and 1,1,1-trifluoro-2-phenylbut-3-yn-2-yl acetate.

Kinetic Resolution of Tertiary Alcohols: Highly Enantioselective Access to 3‐Hydroxy‐3‐Substituted Oxindoles

Enantioselektiv: Die erste hoch enantioselektive kinetische Racematspaltung von 3-Hydroxyoxindolen wurde mittels oxidativer Veresterung in Gegenwart eines N-heterocyclischen Carbens erreicht (siehe Bild). Die Methode liefert 3-substituierte Oxindole in hervorragender Eantiomerenreinheit. S=Selektivität As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Kinetic Resolution of Tertiary Alcohols: Highly Enantioselective Access to 3‐Hydroxy‐3‐Substituted Oxindoles

Enantioselective: The first highly enantioselective kinetic resolution of 3-hydroxy-3-substituted oxindoles has been developed through oxidative esterification catalyzed by a N-heterocyclic carbene (see picture). This method uses a simple procedure and provides 3-hydroxy-oxindoles with various substituents at the 3-position in excellent enantiopurity. S=selectivity.

Rational Protein Design of Paenibacillus barcinonensis Esterase EstA for Kinetic Resolution of Tertiary Alcohols

AbstractProtein engineering is a very powerful tool to optimize enzymes for specific applications and thus provide important chiral building blocks such as tertiary alcohols. By use of structural comparisons, esterase from Paenibacillus barcinonensis (EstA) was engineered to convert tertiary alcohol esters with excellent enantioselectivity. Whereas the wild‐type enzyme converts 1,1,1‐trifluoro‐2‐phenylbut‐3‐yn‐2‐yl acetate with very low activity and enantioselectivity (E=12, at 4 °C), several mutants show a significantly increased enantioselectivity, for example E>100 for mutant EstA–AGA, under the same reaction conditions. Furthermore, the range of tertiary alcohols obtained in enantiopure form was also broadened for EstA mutants.

Rational protein design of Paenibacillus barcinonensis esterase EstA for kinetic resolution of tertiary alcohols

Rational protein design of Paenibacillus barcinonensis esterase EstA for kinetic resolution of tertiary alcohols

Enzymatic Synthesis of Optically Active Tertiary Alcohols: Expanding the Biocatalysis Toolbox

Enantiopure tertiary alcohols are very valuable building blocks for the synthesis of many different natural products and pharmaceuticals. As a consequence, several chemical and enzymatic strategies to afford such chiral structures have been described. Promising enzymatic approaches with agents such as epoxide hydrolases, dehalogenases and hydroxynitrile lyases have been reported, as well as dihydroxylation by microorganisms. Apart from those valuable options, the hydrolase-based kinetic resolution of tertiary alcohols has been known for the last three decades, as several wild-type enzymes have been reported to be able to accept these sterically hindered molecules. More recently, the existence of an amino acid motif within an enzyme's active site has been identified as highly relevant for the acceptance of such bulky structures. This discovery clearly facilitates the identification of novel biocatalysts for this application. Although several tertiary alcohols have been successfully resolved with wild-type biocatalysts, enantioselectivities have often been too low for synthetic purposes. These limitations have recently been overcome by accessing enzymes from the metagenome through directed evolution or by rational protein design. This minireview describes the state of the art in this area, highlighting aspects of basic academic research into the practical application of biocatalysts for the synthesis of optically active tertiary alcohols.

Enzymatic alcoholysis of alkoxymethyl alkanoates: a possible approach for the kinetic resolution of tertiary alcohols

The pivaloyloxymethyl and butanoyloxymethyl derivatives of tert-butanol and linalool ( 1, 4) are readily accepted by hydrolases. Linalool derivative 4b is alcoholysed stereoselectively by Candida rugosa lipase (E=9.7).