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。     

(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.     

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 .     

Covalent Organic Frameworks Based Photoenzymatic Nano-reactor for Asymmetric Dynamic Kinetic Resolution of Secondary Amines

Bio-catalysis represents a highly efficient and stereoselective method for the synthesis of valuable chiral compounds, however, the poor stability and limited reaction types of free enzymes restrict their wide application in industrial production. In this work, to overcome these problems, a multifunctional photoenzymatic nanoreactor CALB@COF-Ir was developed through the encapsulation of Candida antarctica lipase B (CALB) in a photosensitive covalent organic framework COF-Ir . This bio-nanocluster serves as efficient catalysts in asymmetric dynamic kinetic resolution (DKR) of secondary amines to give a series of chiral amines in high yields (up to 99 %) and enantioselectivities (up to 99 % ee). The well-designed COF-Ir not only acts as safety cover to prevent CALB from deactivation but promotes racemization of secondary amines via photo-induced hydrogen atom transfer (HAT) process. Photoelectric characterization and TDDFT calculation revealed that (ppy)₂Ir units in COF-Ir play crucial role in this photocatalytic system which enhance its photo-redox properties through facilitating the separation between photoelectrons (e⁻) and holes (h⁺). Furthermore, the heterogeneous photoenzymatic nanoreactor could be recycled for five rounds with slight decline of catalytic reactivity.     

Highly Efficient Kinetic Resolution of Aryl-Alkenyl Alcohols by Ru-Catalyzed Hydrogen Transfer

No matter through asymmetric reduction of ketones or kinetic resolution of secondary alcohols, enantioselective synthesis of the corresponding secondary alcohols is challenging when the two groups attached to the prochiral or chiral centers are spatially or electronically similar. For examples, dialkyl (sp³ vs. sp³), diaryl (sp² vs. sp²), and aryl-alkenyl (sp² vs. sp²) alcohols are difficult to produce with high enantioselectivities. By exploiting our recently developed Ru-catalysts of minimal stereogenicity, we reported herein a highly efficient kinetic resolution of aryl-alkenyl alcohols through hydrogen transfer. This method enabled such versatile chiral building blocks for organic synthesis as allylic alcohols, to be readily accessed with excellent enantiomeric excesses at practically useful conversions.     

Nonenzymatic Dynamic Kinetic Resolution of Secondary Alcohols via Enantioselective Acylation: Synthetic and Mechanistic Studies

Because of the ubiquity of the secondary carbinol subunit, the development of new methods for its enantioselective synthesis remains an important ongoing challenge. In this report, we describe the first nonenzymatic method for the dynamic kinetic resolution (DKR) of secondary alcohols (specifically, aryl alkyl carbinols) through enantioselective acylation, and we substantially expand the scope of this approach, vis-à-vis enzymatic reactions. Simply combining an effective process for the kinetic resolution of alcohols with an active catalyst for the racemization of alcohols did not lead to DKR, due to the incompatibility of the ruthenium-based racemization catalyst with the acylating agent (Ac(2)O) used in the kinetic resolution. A mechanistic investigation revealed that the ruthenium catalyst is deactivated through the formation of a stable ruthenium-acetate complex; this deleterious pathway was circumvented through the appropriate choice of acylating agent (an acyl carbonate). Mechanistic studies of this new process point to reversible N-acylation of the nucleophilic catalyst, acyl transfer from the catalyst to the alcohol as the rate-determining step, and carbonate anion serving as the Br?nsted base in that acyl-transfer step.     

Facile Synthesis of Enantiopure Sugar Alcohols: Asymmetric Hydrogenation and Dynamic Kinetic Resolution Combined

An unprecedented Ir/f‐amphox‐catalyzed asymmetric hydrogenation of racemic 2,3‐syn‐dihydroxy‐1,4‐diones is presented involving dynamic kinetic resolution, which produces (1R,2R,3R,4R)‐tetraols. This protocol constitutes an efficient and straightforward approach to accessing sugar alcohols bearing four contiguous stereocenters. The strategy exhibits various advantages over existing methods, including excellent yields (up to 98 %), exceptional stereoselectivities (up to 99:1 dr, 99.9 % ee), operational simplicity and substrate generality. Moreover, the nature of the reaction was revealed as a stepwise transformation by in situ Fourier‐transform infrared spectroscopy and isolation of intermediates.     

Ruthenium‐Catalyzed Oxidative Kinetic Resolution of Unactivated and Activated Secondary Alcohols with Air as the Hydrogen Acceptor at Room Temperature

Enantiopure alcohols are versatile building blocks for asymmetric synthesis and the kinetic resolution (KR) of racemic alcohols is a reliable method for preparing them. Although many KR methods have been developed, oxidative kinetic resolution (OKR), in which dioxygen is used as the hydrogen acceptor, is the most atom‐efficient. Dioxygen is ubiquitous in air, which is abundant and safe to handle. Therefore, OKR with air has been intensively investigated and the OKR of benzylic alcohols was recently achieved by using an Ir catalyst without any adjuvant. However, the OKR of unactivated alcohols remains a challenge. An [(aqua)Ru(salen)] catalyzed OKR with air as the hydrogen acceptor was developed, in which the aqua ligand is exchanged with alcohol and the Ru complex undergoes single electron transfer to dioxygen and subsequent alcohol oxidation. This OKR can be applied without any adjuvant to activated and unactivated alcohols with good to high enantioselectivity. The unique influence of substrate inhibition on the enantioselectivity of the OKR is also described.     

Rhodium-Catalyzed Asymmetric [2+2+2] Cycloaddition of 1,6-Enynes with Racemic Secondary Allylic Alcohols through Kinetic Resolution

It has been established that a cationic rhodium(I)/P-phos complex catalyzes the asymmetric [2+2+2] cycloaddition of 1,6-enynes with racemic secondary allylic alcohols to produce the corresponding chiral bicyclic cyclohexenes, possessing three stereogenic centers, as a single diastereomer with excellent ee values. Mechanistic experiments revealed that the present cycloaddition proceeds through the kinetic resolution of the racemic secondary allylic alcohols, in which one enantiomer preferentially reacts with the 1,6-enyne.     

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。     

Kinetic Resolution of Racemic Allylic Alcohols by Catalytic Asymmetric Substitution of the OH Group with Monosubstituted Hydrazines

A new strategy has been established for the kinetic resolution of racemic allylic alcohols through a palladium/sulfonyl‐hydrazide‐catalyzed asymmetric OH‐substitution under mild conditions. In the presence of 1 mol % [Pd(allyl)Cl]₂, 4 mol % (S)‐SegPhos, and 10 mol % 2,5‐dichlorobenzenesulfonyl hydrazide, a range of racemic allylic alcohols were smoothly resolved with selectivity factors of more than 400 through an asymmetric allylic alkylation of monosubstituted hydrazines under air at room temperature. Importantly, this kinetic resolution process provided various allylic alcohols and allylic hydrazine derivatives with high enantiopurity.     

Chiral Ligands Derived from Monoterpenes: Application in the Synthesis of Optically Pure Secondary Alcohols via Asymmetric Catalysis

The preparation of optically pure secondary alcohols in the presence of catalysts based on chiral ligands derived from monoterpenes, such as pinenes, limonenes and carenes, is reviewed. A wide variety of these ligands has been synthesized and used in several catalytic reactions, including hydrogen transfer, C?C bond formation via addition of organozinc compounds to aldehydes, hydrosilylation, and oxazaborolidine reduction, leading to high activities and enantioselectivities.     

Deoxygenative Borylation of Secondary and Tertiary Alcohols

Two different approaches for the deoxygenative radical borylation of secondary and tertiary alcohols are presented. These transformations either proceed through a metal‐free silyl‐radical‐mediated pathway or utilize visible‐light photoredox catalysis. Readily available xanthates or methyl oxalates are used as radical precursors. The reactions show broad substrate scope and high functional‐group tolerance, and are conducted under mild and practical conditions.     

酶-过渡金属配合物催化的动态动力学拆分研究进展

动态动力学拆分是合成具有光学活性化合物最方便和最有效的方法之一. 酶和金属配合物的结合扩展了这个方法的使用范围, 该方法的主要特征是用酶催化拆分和金属催化原位外消旋化未反应的底物, 克服了经典动力学拆分最高产率只有50%的缺陷. 概述了近几年这方面的研究进展.