Chiral Cobalt‐Catalyzed Enantiomer‐Differentiating Oxidation of Racemic Benzoins by Using Molecular Oxygen as Stoichiometric Oxidant

An efficient enantioselective oxidative reaction catalyzed by a chiral cobalt complex has been developed by using molecular oxygen as the stoichiometric oxidant (see scheme). The very mild reaction conditions of the catalytic system provide access to a wide range of benzoins (α‐hydroxyketones) in high yield and excellent enantioselectivity (s (k_f/k_s) up to 47). This method is very versatile because the sole by‐product of our oxidation process is water, which makes our system more eco‐friendly and green.

     

Enantioselective Allylic Oxidation of Olefins Using Chiral Quinolinyl‐oxazoline Copper Complex Catalysts

Copper complexes of chiral quinolinyl‐oxazoline have been studied as the catalysts for enantioselective allylic oxidation of cycloalkenes with tert‐butyl perbenzoate. Using 5 mol% of these chiral catalysts, optical active allylic benzoates were obtained in moderate enantiomeric excesses. CuOTf prepared in situ, CuClO₄ and CuPF₆ were found to be good precatalysts in acetone.     

有机相中的酶促拆分过程

总结了有机溶剂中的酶催化研究进展, 讨论了影响有机溶剂中酶促不对称转化过程对映体选择性的因素和拆分动力学。     

Enantiodivergent Atroposelective Synthesis of Chiral Biaryls by Asymmetric Transfer Hydrogenation: Chiral Phosphoric Acid Catalyzed Dynamic Kinetic Resolution

Reported herein is an enantiodivergent synthesis of chiral biaryls by a chiral phosphoric acid catalyzed asymmetric transfer hydrogenation reaction. Upon treatment of biaryl lactols with aromatic amines and a Hantzsch ester in the presence of chiral phosphoric acid, dynamic kinetic resolution (DKR) involving a reductive amination reaction proceeded smoothly to furnish both R and S isomers of chiral biaryls with excellent enantioselectivities by proper choice of hydroxyaniline derivative. This trend was observed in wide variety of substrates, and various chiral biphenyl and phenyl naphthyl adducts were synthesized with satisfactory enantioselectivities in enantiodivergent fashion. The enantiodivergent synthesis of synthetically challenging, chiral o‐tetrasubstituted biaryls were also accomplished, and suggests high synthetic potential of the present method.     

仲醇的氧化动力学拆分

光学活性仲醇是非常重要的合成多种具有药物和生物活性化合物的原料和关键中间体,它们可通过外消旋仲醇的氧化动力学拆分获得。本文按氧化剂和手性催化剂的类别分类综述了近年来通过氧化动力学拆分获得光学活性仲醇方法的进展,并对一些方法的机理进行了描述。对以(-)-金雀花碱-钯(Ⅱ)、金雀花碱类似物-钯(Ⅱ)、N-杂环卡宾(NHC)-钯(Ⅱ)、手性双官能团-铱配合物以及手性(ON)-钌(salen)配合物催化的分子氧为氧化剂的仲醇的氧化动力学拆分进行了充分讨论。此外,还讨论了手性salen-锰(Ⅲ)催化二乙酰基碘苯以及通过不对称氢转移的方法对仲醇的氧化动力拆分。可以发现,(-)-金雀花碱-钯(Ⅱ)-分子氧体系在目前所有仲醇氧化动力学拆分体系中表现最佳。用于仲醇氧化动力学拆分的高效体系仍有待进一步开发。     

Dynamic Kinetic Resolution of 2,3‐Dihydrobenzo[b]furans: Chemoenzymatic Synthesis of Analgesic Agent BRL 37959

An efficient asymmetric synthesis of (S)‐2,3‐dihydrobenzo[b]furan‐3‐carboxylic acid ( 8 a ) and (S)‐5‐chloro‐2,3‐dihydrobenzo[b]furan‐3‐carboxylic acid ( 8 b ) was established. Key to the success was the highly stereoselective enzymatic kinetic resolution of the corresponding methyl or ethyl esters that was further developed into a dynamic process. As a reliable and fast tool for analysing the enantiomeric excess, HPLC coupled with a CD detector was utilized. The route was completed by a Friedel–Crafts acylation of ethyl (S)‐5‐chloro‐2,3‐dihydrobenzo[b]furan‐3‐carboxylate ( 7 c ) followed by saponification leading to (S)‐5‐chloro‐2,3‐dihydrobenzo[b]furan‐3‐carboxylic acid ( 2 ), an analgesic agent.     

Kinetic Resolution of sec‐Thiols by Enantioselective Oxidation with Rationally Engineered 5‐(Hydroxymethyl)furfural Oxidase

Various flavoprotein oxidases were recently shown to oxidize primary thiols. Herein, this reactivity is extended to sec‐thiols by using structure‐guided engineering of 5‐(hydroxymethyl)furfural oxidase (HMFO). The variants obtained were employed for the oxidative kinetic resolution of racemic sec‐thiols, thus yielding the corresponding thioketones and nonreacted R‐configured thiols with excellent enantioselectivities (E≥200). The engineering strategy applied went beyond the classic approach of replacing bulky amino acid residues with smaller ones, as the active site was additionally enlarged by a newly introduced Thr residue. This residue established a hydrogen‐bonding interaction with the substrates, as verified in the crystal structure of the variant. These strategies unlocked HMFO variants for the enantioselective oxidation of a range of sec‐thiols.     

A Cationic Ruthenium Complex for the Dynamic Kinetic Resolution of Secondary Alcohols

A synthetic protocol making use of a well‐defined cationic ruthenium complex 2 enabling the racemization of enantiomerically pure secondary alcohols in the presence of a weak base (K₂CO₃) is described. The compatibility of 2 with Candida Antarctica lipase B (Novozym 435) allows the development of an efficient dynamic kinetic resolution of sec‐alcohols in the absence of an additional strong base. This procedure involves the first example of a dynamic kinetic resolution of alcohols in the presence of a cationic ruthenium catalyst. In addition, we describe the conversion of ketones to the enantioenriched acetates in a one‐pot reaction, probing the versatility of complex 2 .     

Design,Synthesis, and Application of a Chiral Sulfinamide Phosphine Catalyst for the Enantioselective Intramolecular Rauhut–Currier Reaction

A novel class of chiral sulfinamide phosphine catalysts (Xiao‐Phos) are reported, which can be easily prepared from inexpensive commercially available starting materials. The Xiao‐Phos catalysts showed good performance in enantioselective intramolecular Rauhut–Currier reactions, generating α‐methylene‐γ‐butyrolactones in high yields with up to 99 % ee under mild conditions. Moreover, kinetic resolution and parallel kinetic resolution were also observed with the use of two different substituted racemic precursors.     

From Structural Models of Galactose Oxidase to Homogeneous Catalysis: Efficient Aerobic Oxidation of Alcohols

Two reaction pathways are catalyzed by the dinuclear copper(II )–phenoxyl complex 1 —a functional model for the metalloenzyme galactose oxidase—by the oxidation of primary and secondary alcohols with dioxygen (air) in homogeneous solution to their corresponding aldehydes or ketones and/or 1,2-glycols (oxidative C–C coupling). The reduction product formed is H₂O₂, not water.     

Making the Silylation of Alcohols Chiral: Asymmetric Protection of Hydroxy Groups

The non-enzymatic kinetic resolution of racemic mixtures of alcohols by silylation had been unknown before the turn of the century. This stands in stark contrast to established acylation techniques. The same applies to the related desymmetrization of diols. This might come as a surprise, given the significance of silyl ethers as protecting groups in multistep synthesis of complex molecules. The situation changed after a seminal report by Ishikawa nearly twenty years ago. Since then, enantioselective silylation of alcohols has matured and grown into an independent research field with organocatalytic and transition-metal-catalyzed approaches providing powerful solutions. This Minireview summarizes these recent advances with particular emphasis on the stereoselective dehydrogenative coupling of alcohols and hydrosilanes.     

Extraction of Phenylalanine Enantiomers by Aqueous Two Phase Systems Containing Combinatorial Chiral Selector

In order to obtain a better enantioselectivity of phenylalanine enantiomers and establish the optimal chiral extraction conditions, the distribution behavior was investigated in aqueous two‐phase systems which were composed of polyethylene glycol and ammonium sulfate containing combinatorial chiral selector: β‐cyclodextrin and HP‐β‐cyclodextrin. The influence of the molar concentration ratio of combinatorial chiral selectors, the total molar concentration of combinatorial chiral selectors, pH value, buffer type and its concentration were thoroughly studied, respectively. The results show that the enantioselectivity reaches 1.53 under the optimal chiral extraction conditions. This extraction is a potential economical and effective way for chiral resolution.     

三溴化三乙基苄铵对于苯偶姻的氧化反应

作者前曾报道,三溴化三乙基苄铵(PhCH_2Et_3NBr_3~-,TEBABr_3,1)和三碘化三乙基苄铵(TEBAL_3)能作为有效的溴代和碘代试剂而与芳胺反应,以高产率生成多溴代和多碘代芳胺。在进一步对TEBABr_3在有机合成