Copper Complex of Aminoisoborneol Schiff Base Cu2(SBAIB‐d)2: An Efficient Catalyst for Direct Catalytic Asymmetric Nitroaldol (Henry) Reaction

A new bifunctional copper complex of the aminoisoborneol Schiff base – Cu₂(SBAIB‐d)₂ – has been developed for the effective direct catalytic asymmetric Henry reaction. One mol% of this catalyst produces the expected Henry products in high yields (up to 99%) with excellent enantioselectivities (up to 98% ee). The utility of the present catalyst was also extended to the Henry reaction with nitroethane and 1‐nitropropane that furnished the corresponding products in moderate to high yields (up to 99%) with moderate to high enantioselectivities of syn (up to 98% ee) and anti (up to 98% ee) diastereomers. The highlights of this catalytic system are easy manipulation, air and moisture tolerance, the need for 1 mol% of an easily synthesizable catalyst and the high enantioselectivities achieved for a wide range of substrates.     

Dynamic Kinetic Resolution of Primary Alcohols with an Unfunctionalized Stereogenic Center in the β‐Position

Primary alcohols with an unfunctionalized stereogenic center in the β‐position undergo an enzyme‐ and metal‐catalyzed dynamic kinetic resolution (DKR). The in situ racemization of the primary alcohol, required for the DKR, takes place via: (i) ruthenium‐catalyzed dehydrogenation of the alcohol, (ii) enolization of the aldehyde formed, and (iii) ruthenium‐catalyzed readdition of hydrogen to the aldehyde. The present method widens the scope of metal‐ and enzyme‐catalyzed DKR, which has so far been limited to α‐chiral alcohol and amine derivatives.     

Organocatalyzed Dynamic Kinetic Resolution

In the last decade, the first examples of organocatalyzed dynamic kinetic resolution (DKR) processes have been described, considerably expanding the synthetic scope of this powerful process which allows the resolution of racemic compounds with up to 100% yield. Today, a significant number of chiral organocatalysts are available that afford excellent levels of stereocontrol in various reactions evolving through DKR that could only previously be achieved using biocatalysts. The goal of the present review is to cover the works dealing with organocatalytic reactions evolving through DKR. This review is subdivided into four sections, according to the different types of organocatalysts employed in these reactions, such as Cinchona alkaloid catalysts, catalysts derived from amino acids, hydroxy acid catalysts, and miscellaneous organocatalysts. Abbreviations: Ac: acetyl; Ar: aryl; BINOL: 1,1′‐bi‐2‐naphthol; Bn: benzyl; Bu: butyl; c: cyclo; Cbz: benzyloxycarbonyl; CPME: cyclopentyl methyl ether; Cy: cyclohexyl; DABCO: 1,4‐diazabicyclo[2.2.2]octane; de: diastereomeric excess; DKR: dynamic kinetic resolution; DMF: dimethylformamide; Dmpe: 1,2‐bis(dimethylphosphino)‐ethane; DMSO: dimethyl sulfoxide; DYKAT: dynamic kinetic asymmetric transformation; ee: enantiomeric excess; Et: ethyl; Fmoc: 9‐fluorenylmethoxycarbonyl; Fu: furyl; Me: methyl; MTBE: methyl tert‐butyl ether; Naph: naphthyl; Pent: pentyl; Ph: phenyl; PMP: p‐methoxyphenyl; Pr: propyl; TBHP: tert‐butyl hydroperoxide; TEA: triethylamine; THF: tetrahydrofuran; Thio: thiophene; TMS: trimethylsilyl; Tol: tolyl.     

酶催化外消旋体的动态动力学拆分反应研究进展

外消旋体的动态动力学拆分（DKR）是制备手性化合物的重要方法之一,过去多用化学催化剂进行反应,近年来生物催化剂的引入大大提高了DKR的效率和收率。系统地介绍了DKR的原理及酶催化外消旋体的动力学拆分反应的最新进展。     

动态动力学拆分法制备(S)-(+)-呋虫胺

以(±)-四氢呋喃-3-甲醇与(D)-(+)-10-樟脑磺酰氯反应生成四氢呋喃-3-甲基樟脑磺酸酯,通过动态动力学拆分法得到单一构型四氢呋喃-3-甲基樟脑磺酸酯晶体,将晶体用解离剂解离得到(S)-(+)-四氢呋喃-3-甲醇,ee值99,收率85%,进一步与1,5-二甲基-2-硝基亚胺六氢-1,3,5-三嗪反应得到(S)-(+)-呋虫胺。     

天然固定化木瓜脂肪酶催化芳香仲醇动力学拆分的研究

将木瓜来源的廉价天然固定化脂肪酶CPL用于手性拆分芳香仲醇,以4-苯基-2-丁醇作为模式底物,考察了反应温度、反应溶剂、酰基供体以及底物摩尔比对CPL拆分能力的影响,结果表明,适宜的反应温度30~45℃,酰基供体为活性乙烯酯,正己烷或环己烷作为反应溶剂,底物/酰基供体摩尔比1∶2,在该条件下底物的转化率接近50%,e.es大于99%,反应的对映体比值E大于200。CPL对其他结构类似的芳香仲醇也具有很好的拆分能力。该研究为手性芳香仲醇的酶催化制备提供了新的催化剂选择。     

Diastereoselective and Highly Enantioselective Henry Reactions using C1‐Symmetrical Copper(II) Complexes

Catalytic Henry reactions of aliphatic aldehydes and prochiral nitro compounds were investigated using copper(II) complexes of 14 C₁‐symmetrical ligands derived from (1R,2R)(−)‐diaminocyclohexane. β‐Nitro alcohols with syn:anti ratios of up to 5.7 and excellent ee values for both diastereosimers were obtained.     

Asymmetric Synthesis of Substituted Thiolanes through Domino Thia‐Michael–Henry Dynamic Covalent Systemic Resolution using Lipase Catalysis

Dynamic systems based on consecutive thia‐Michael and Henry reactions were generated and transformed using lipase‐catalyzed asymmetric transformation. Substituted thiolane structures with three contiguous stereocenters were resolved in the process in high yields and high enantiomeric excesses.

     

Combined Enzyme and Transition-Metal Catalysis for Dynamic Kinetic Resolutions

The preparation of optically pure alcohols, axially chiral allenes, and amine derivatives by using enzymes and transition-metal catalysts through dynamic kinetic resolution (DKR) is reviewed. After a general introduction into enzymatic kinetic resolutions and racemizations catalyzed by transition-metal complexes, selected examples of DKRs are presented, from early work to more recent outstanding contributions, and also applications of this approach.     

Charge‐Transfer Interactions: An Efficient Tool for Recycling Bis(oxazoline)‐Copper Complexes in Asymmetric Henry Reactions

An anthracenyl‐modified chiral bis(oxazoline) copper complex has been demonstrated to efficiently promote nitroaldol reactions between structurally varying aldehydes and nitromethane or nitroethane. The catalyst was recovered through formation of a charge transfer complex between the chiral ligand and trinitrofluorenone and its subsequent precipitation with pentane. The efficiency of this procedure was proved through several consecutive catalytic cycles that allowed the sturdy formation of the expected product with a high enantioselectivity. The catalyst′s stability was also put to the test in an original multi‐substrate procedure. Following the same recovery concept, a new heterogeneous procedure was tested for which trinitrofluorenone was covalently linked to a silica support. Asymmetric heterogeneous catalysis was performed under these conditions as one of the few examples demonstrating the potential catalyst recycling in nitroaldol reactions through reversible, non‐covalent interactions.     

Heterogeneous Raney Nickel and Cobalt Catalysts for Racemization and Dynamic Kinetic Resolution of Amines

Raney metals were studied as heterogeneous catalysts for racemization and dynamic kinetic resolution (DKR) of chiral amines, as an alternative to metals like palladium or ruthenium. Both Raney nickel and cobalt were able to selectively racemize various chiral amines with high selectivity. In the racemization of benzylic primary amines, the minor formation of side products, e.g., secondary amines, can be suppressed by varying the hydrogen pressure. In the racemization of aliphatic amines over Raney catalysts, the selectivity is very high, with the enantiomeric amine as the sole product. DKR of racemic aliphatic amines can be performed with immobilized Candida antarctica lipase B and Raney nickel in one pot; for 2‐hexylamine, a yield of 95 % of the acetylated amide was achieved, with 97 % ee. Attention is devoted to the compatibility of the enzyme and the metal catalyst during the DKR. For benzylic primary amines, a two‐pot process is proposed in which the liquid is alternatingly shuttled between two vessels containing the solid racemization catalyst and the biocatalyst. After 4 such cycles, the amide of (R)‐1‐phenylethylamine was obtained with 94 % yield and more than 90 % ee.     

Asymmetric Hydrosilylation of Prochiral Ketones Catalyzed by Nanocrystalline Copper(II) Oxide

Asymmetric hydrosilylation of aryl alkyl ketones to afford chiral secondary alcohols with good yields and excellent enantioselectivity is realized by using nanocrystalline copper(II) oxide and BINAP in the presence of organosilanes as the stoichiometric reducing agents.     

Enantioselective Synthesis of Chiral β‐Aryloxy Alcohols by Ruthenium‐Catalyzed Ketone Hydrogenation via Dynamic Kinetic Resolution (DKR)

A highly efficient enantioselective synthesis of chiral β‐aryloxy alcohols by the {RuCl₂[(S)‐SDP][(R,R)‐DPEN]} [(S_a,R,R)‐ 1a ; SDP=7,7′‐bis(diarylphosphino)‐1,1′‐spirobiindane; DPEN=trans‐1,2‐diphenylethylenediamine] complex‐catalyzed asymmetric hydrogenation of racemic α‐aryloxydialkyl ketones via dynamic kinetic resolution (DKR) has been developed. Enantioselectivities of up to 99% ee with good to high cis/anti‐selectivities (up to>99:1) were achieved.     

Kinetic Resolution of 1‐Biaryl‐ and 1‐(Pyridylphenyl)alkan‐1‐ols Catalysed by the Lipase B from Candida antarctica

Lipase B from Candida antarctica (CAL‐B) catalyses the highly enantioselective (E>200) transesterification of some 1‐biaryl‐2‐yl‐, ‐3‐yl‐, and ‐4‐ylethanols and ‐propan‐1‐ols, as well as 1‐(o‐, m‐, and p‐pyridylphenyl)ethanols, 6 , with vinyl acetate, Kazlauskas' rule being obeyed in all cases. meta and para‐Substituted substrates were transformed within several hours (conversion degree ranging from 23–50%), reaction rates for propan‐1‐ol derivatives being slower than those for ethanol derivatives. Transesterifications of ortho‐substituted alcohols took several days and were accompanied by a chemoenzymatic side reaction: the formation of another acetate derived from the hemiacetal between 6 and acetaldehyde coming from vinyl acetate. This side reaction was suppressed in the presence of isopropenyl acetate as acyl donor, conversion degrees for transesterification ranging from 20–40% after ten days (E>200). The usefulness of (R)‐ 6p as ligand in the asymmetric addition of diethylzinc to benzaldehyde was also demonstrated.     

Reusable Chiral Dicationic Chromium(III) Salen Catalysts for Aminolytic Kinetic Resolution of trans‐Epoxides

A series of new recyclable chiral dicationic chromium(III) salen complexes 1 – 10 bearing different substituents, viz., hydrogen, methyl, tert‐butyl, triphenylphosphinomethyl, triethylaminomethyl, methylimidazolium, methylpyridinium, methyl‐N,N‐dimethylpyridinium at the 3,3′‐ and 5,5′‐ positions of the salen unit with (1S,2S)‐(+)‐1,2‐diaminocyclohexane, (1S,2S)‐(−)‐1,2‐diphenyl‐1,2‐diaminoethane, and (S)‐(−)‐1,1′‐binaphthyl‐2,2′‐diamine collars have been synthesized and characterized by various physico‐chemical methods. These complexes were used as catalysts for the highly enantioselective aminolytic kinetic resolution of racemic trans‐epoxides with different anilines as nucleophiles at room temperature. With the use of catalyst 3 , anti‐β‐amino alcohols were obtained in excellent yields (>99% with respect to the nucleophile) and enantioselectivities (ee>99%) with the concomitant recovery of corresponding epoxides in high optical purity (ee up to >99%) and quantitative yields in 12 h. The catalyst 3 is recyclable in the aminolytic kinetic resolution process and worked well up to six cycles with retention of enantioselectivity.     

Transfer Hydrogenation of α‐Branched Ketimines: Enantioselective Synthesis of Cycloalkylamines via Dynamic Kinetic Resolution

The transfer hydrogenation of 2‐substituted bicyclic and monocyclic ketimines using HCO₂H/ Et₃N as the hydrogen source and TsDPEN‐based Ru(II) and Ir(III) catalysts proceeds with dynamic kinetic resolution to afford the corresponding cis‐cycloalkylamines with moderate to excellent levels of diastero‐ and enantioselectivity. A “one‐pot” procedure starting from ketones as starting materials with in situ formation of the reacting imines has also been developed.     

Enantioselective Synthesis of 4‐(Dimethylamino)pyridines through a Chemical Oxidation‐Enzymatic Reduction Sequence. Application in Asymmetric Catalysis

Enantiomerically pure 4‐(dimethylamino)‐3‐(1‐hydroxyalkyl)pyridines and 4‐(dimethylamino)‐3‐[hydroxy(phenyl)methyl]pyridine have been prepared through efficient chemoenzymatic routes. For this purpose different lipases and oxidoreductases have been tested in the preparation of optically active 4‐chloro derivatives and baker’s yeast was found to be an excellent catalyst for the bioreductions of the corresponding ketones. Their applications as enantioselective nucleophilic catalysts have been studied, important catalytic properties were observed in the stereoselective construction of quaternary centers.