光学活性氰醇的合成研究进展

光学活性氰醇是合成大量医药、农药产品的重要中间体。本文介绍了通过生物或化学催化剂进行外消旋底物的拆分或前手性底物的不对称化来制备光学活性氰醇的方法,重点讨论了有较大发展前景的有机溶剂中脂肪酶催化氰醇酯的动力学拆分的方法。     

胶束催化体系中的对映选择性环醚化反应

The enantioselective cycloetherification of substituted keto phenols into their corresponding dihydrobenzofuran derivatives was carried out using hydrogen peroxide and chiral quaternary ammonium iodide in micellar media. This approach increased the conversion rate of cycloetherification and also widened the scope of this particular reaction for various substituted keto phenols with electron withdrawing as well as electron donating functionalities. The use of a surfactant in the cycloetherification reaction ...     

Kinetic resolution of cyanohydrins via enantioselective acylation catalyzed by lipase PS-30

By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic cyanohydrins has been achieved via enantioselective acylation. The values of kinetic enantiomeric ratio (E) reached up to 314. Substituent effect is also briefly discussed.     

From central to planar chirality,the first example of atropenantioselective cycloetherification

Using chiral quaternary ammonium hydroxide as base, cycloetherification of linear achiral diarylheptanoid 5, by way of an intramolecular SNAr reaction, provides enantiomerically enriched cyclophane 6 in good to excellent yield.     

Exceptionally Simple Enantioselective Syntheses of Chiral Hexa- and Tetracyclic Polyprenoids of Sedimentary Origin

Coupling between a sulfone and an acylsilane fragment (see below) constitutes the first step in the exceptionally short total syntheses of two chiral hexacyclic hydrocarbons isolated from Eocene Messel shale (Germany). Like the first step, subsequent steps also employ a powerful synthetic tactic: polycyclization of a specially constructed chiral, multiply unsaturated oxirane. TBS=tBuMe₂Si.     

A practical high through-put continuous process for the synthesis of chiral cyanohydrins

A practical high through-put continuous process for the synthesis of chiral cyanohydrins is reported. Pretreated almond meal (or other solid raw enzyme sources) was loaded in a column to form a reactor, to which were attached a supplying system to deliver a solution of substrate and HCN in solvent on one end and a collecting-separating system on the other end. By controlling the flowing rate, optimal conditions were achieved for the hydrocyanation of various aromatic carboxaldehydes in a "micro-aqueous" medium to produce chiral cyanohydrins in high yields and high enantiomeric excess (ee) with high substrate/catalyst ratio.     

化学酶法动态动力学拆分胺类化合物研究进展

论述了动态动力学拆分的原理,介绍了化学酶法拆分消旋体胺类化合物的反应和近年来的研究进展;指出手性胺是构成许多中间体的基础化合物,化学酶法动态动力学拆分是制备单一手性胺类化合物的重要方法.     

Highly Enantioselective Kinetic Resolution of Axially Chiral BINAM Derivatives Catalyzed by a Brønsted Acid

A highly efficient strategy for the kinetic resolution of axially chiral BINAM derivatives involving a chiral Brønsted acid‐catalyzed imine formation and transfer hydrogenation cascade process was developed. The kinetic resolution provides a convenient route to chiral BINAM derivatives in high yields with excellent enantioselectivities.     

Lipase-catalyzed kinetic resolution of aryltrimethylsilyl chiral alcohols

Lipase-catalyzed kinetic resolution of aryltrimethylsilyl chiral alcohols through a transesterification reaction was studied. The optimal conditions found for the kinetic resolution of m- and p-aryltrimethylsilyl chiral alcohols, led to excellent results, high conversions (c = 50%), high enantiomeric ratios (E > 200) and enantiomeric excesses for the remaining (S)-alcohol and (R)-acetylated product (>99%). However, kinetic resolution of o-aryltrimethylsilyl chiral alcohols did not occur under the same conditions applied to the other isomers.     

Asymmetric synthesis of both the enantiomers of antidepressant venlafaxine and its analogues

Chemoenzymatic asymmetric synthesis of antidepressant agent venlafaxine and its analogue have been reported in this communication. The main highlight of the reported synthesis is the stereoselective synthesis of cyanohydrins by (S)-hydroxynitrile lyase (Hevea brasiliensis) followed by lipase catalyzed kinetic resolution.     

New strategy for the asymmetric synthesis of phenyl ketone cyanohydrins: quaternization of cyanohydrins derived from 2-p-tolylsulfinyl benzaldehyde

[reaction: see text] Optically pure functionalized cyanohydrins derived from 1-[2-(p-tolylsulfinyl)phenyl] ethanone can be obtained by the reaction of 2-p-tolylsulfinyl benzaldehyde derived cyanohydrins with bases and further treatment with suitable electrophiles. High yields and excellent stereoselectivities (up to de >98%) were obtained for these remote 1,4-asymmetric induction processes controlled by a sulfinyl chiral inductor.     

Kinetic resolution of acyclic secondary allylic silyl ethers catalyzed by chiral ketones.

Kinetic resolution of acyclic secondary allylic silyl ethers by chiral dioxiranes generated in situ from chiral ketones (R)-1 and (R)-2 and Oxone was investigated. An efficient and catalytic method has been developed for kinetic resolution of those substrates with a CCl(3), tert-butyl, or CF(3) group at the alpha-position. In particular, high selectivities (S up to 100) were observed for kinetic resolutions of racemic alpha-trichloromethyl allylic silyl ethers 7 and 9-15 catalyzed by ketones (R)-2. Both the recovered substrates and the resulting epoxides were obtained in high enantiomeric excess. On the basis of steric and electrostatic interactions between the chiral dioxiranes and the racemic substrates, a model was proposed to rationalize the enantioselectivities and diastereoselectivities in the chiral ketone-catalyzed kinetic resolution process.     

离子液体在不对称催化反应中的应用进展

综述了近年来离子液体在不对称催化反应中的应用,包括不对称Aldol反应、不对称氟化反应、酶催化的不对称还原反应、不对称催化氢化反应、不对称硅腈化反应、不对称环丙烷化反应、烯丙基的不对称取代反应、环氧化物的不对称开环反应、不对称环氧化反应、烯烃的不对称双羟基化反应、酶催化的醇的动力学拆分。参考文献43篇。     

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。     

Synthesis of New Bifunctional Bis(oxazolines) and Their Application in the Asymmetric Cyanosilylation of Aromatic Ketones

Catalytic asymmetric synthesis of tertiary cyanohydrins by the addition of cyanide to a wide range of ketones has important synthetic utility, since the resulting optically active cyanohydrins are important intermediates for the synthesis of a variety of valuable classes of chiral compounds. The application of oxazoline in asymmetric cyanosilylation has seldom reported in comparation with other reactions.[1] Recently, polymer-supported pyridine-bis(oxazoline) ytterbium complex was reported to catalyze cyanosilylation of benzaldehyde.     

光学活性芳族氰醇的合成及其稳定性的研究

光学活性芳族氰醇以及由它转变而成的α-羟基酸、α-羟基酯、α-羟基酮和β-羟基胺等光学活性异构体都是重要的农药和医药中间休,从实用观点看,利用催化不对称合成来制取光活性氰醇,更具有重要意义。近年来,环状二肽Cyclo[L(D)-Phe-L(D)-His]用于催化芳族氰醇的不对称合成,由于具有与D-羟腈酶相类似的高活性和高对映选择性,尤为     

Kinetic Resolution and Dynamic Kinetic Resolution of Chromene by Rhodium‐Catalyzed Asymmetric Hydroarylation

A highly efficient kinetic resolution and dynamic kinetic resolution of chromene is reported for the first time and they procced by a rhodium‐catalyzed asymmetric hydroarylation pathway. This new approach offers versatile access to various chiral 2,3‐diaryl‐chromanes containing vicinal stereogenic centers, as well as the recovered chiral flavenes, in high yields with excellent ee values (s factor up to 532). Particularly noteworthy is that this strategy can be further extended to the establishment of a dynamic version of the kinetic resolution of chromene acetals and allows complete access to chiral isoflavanes and α‐aryl hydrocoumarins.     

Nickel-Catalyzed Kinetic Resolution of Racemic Unactivated Alkenes via Enantio-, Diastereo-, and Regioselective Hydroamination

Kinetic resolution is a powerful strategy for the isolation of enantioenriched compounds from racemic mixtures, and the development of selective catalytic processes is an active area of research. Here, we present a nickel-catalyzed kinetic resolution of racemic α-substituted unconjugated carbonyl alkenes via the enantio-, diastereo-, and regioselective hydroamination. This protocol affords both chiral α-substituted butenamides and syn-β^2,3-amino acid derivatives with high enantiomeric purity (up to 99 % ee) and selectivity factor up to >684. The key to the excellent kinetic resolution efficiency is the distinctive architecture of the chiral nickel complex, which enables successful resolution and enantioselective C−N bond construction. Mechanistic investigations reveal that the unique structure of the chiral ligand facilitates a rapid migratory insertion step with one enantiomer. This strategy provides a practical and versatile approach to prepare a wide range of chiral compounds.     

Enzymatic kinetic resolution of racemic cyanohydrins via enantioselective acylation

Enzymatic kinetic resolution of a series of aromatic and aliphatic cyanohydrins in organic media has been investigated. The behavior of potential lipases, molecular sieves, acyl reagent, reaction temperature, and organic solvents on the kinetic resolution was studied. The influence of substrate structure, steric, and electronic nature and position of the aryl substituent on the enantioselectivity was discussed. Under the optimized reaction conditions, good enantioselectivity could be achieved for most of the investigated compounds. Specifically, substrates 1a, 1c, 1d, 1f, 1u could be resolved with the kinetic enantiomer ratio (E) higher than 200.     

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.