Assembled enantioselective catalysts for carbonyl-ene reactions

A new strategy for generating assembled polymeric chiral titanium complexes using linked bis-BINOL ligands have been developed, and the assembled catalysts showed excellent enantioselectivity (up to 96.5% ee) for carbonyl-ene reaction under heterogeneous conditions to afford corresponding α-hydroxy esters in high yield. The linkers between two BINOL units of the ligands in the assembled catalysts were found to have significant impact on the enantioselectivity of reaction, which demonstrated the importance of the supramolecular structures of the assemblies for their catalytic behaviours.     

The synthesis of silica-supported chiral BINOL: Application in Ti-catalyzed asymmetric addition of diethylzinc to aldehydes

Chiral BINOL was covalently anchored on two different pore sized mesoporous silica (SBA-15 (7.5 nm) and MCF (14 nm)). These heterogenized ligands were used in Ti-catalyzed asymmetric addition of diethylzinc to aldehydes. High catalytic activity with excellent enantioselectivity (up to 94% ee) for secondary alcohols was achieved using MCF supported chiral BINOL under heterogeneous reaction conditions. Good to excellent enantioselectivity (ee, 68–91%) was also achieved with various small to bulkier aldehydes. The MCF supported catalyst was reused in multiple catalytic runs without loss of enantioselectivity.     

Self-supported chiral titanium cluster (SCTC) as a robust catalyst for the asymmetric cyanation of imines under batch and continuous flow at room temperature

A robust heterogeneous self-supported chiral titanium cluster (SCTC) catalyst and its application in the enantioselective imine-cyanation/Strecker reaction is described under batch and continuous processes. One of the major hurdles in the asymmetric Strecker reaction is the lack of availability of efficient and reusable heterogeneous catalysts that work at room temperature. We exploited the readily hydrolyzable nature of titanium alkoxide to synthesize a self-supported chiral titanium cluster (SCTC) catalyst by the controlled hydrolysis of a preformed chiral titanium-alkoxide complex. The isolated SCTC catalysts were remarkably stable and showed up to 98 % enantioselectivity (ee) with complete conversion of the imine within 2 h for a wide variety of imines at room temperature. The heterogeneous catalysts were recyclable more than 10 times without any loss in activity or selectivity. The robustness, high performance, and recyclability of the catalyst enabled it to be used in a packed-bed reactor to carry out the cyanation under continuous flow. Up to 97 % ee and quantitative conversion with a throughput of 45 mg h(-1) were achieved under optimized flow conditions at room temperature in the case of benzhydryl imine. Furthermore, a three-component Strecker reaction was performed under continuous flow by using the corresponding aldehydes and amines instead of the preformed imines. A good product distribution was obtained for the formation of amino nitriles with ee values of up to 98 %. Synthetically useful ee values were also obtained for challenging α-branched aliphatic aldehyde by using the three-component continuous Strecker reaction.     

Multiple dendritic catalysts for asymmetric transfer hydrogenation

The first and second generation multiple dendritic ligands based on chiral diamine were synthesized in a convergent approach and were well-characterized by NMR and MS techniques. Their ruthenium complexes prepared in situ had good solubility in the reaction medium (azeotrope of formic acid and triethylamine) and demonstrated high catalytic activity and enantioselectivity comparable to monomeric catalysts in the asymmetric transfer hydrogenation of ketones and imines. Quantitative yields and for some cases a slightly higher enantioselectivity (up to 98.7% ee) were obtained in the dendritic catalysis. Considering the high local catalyst concentrations at the periphery, diones were tested for the possible synergic reactivity between catalytic units at the surface, while no apparent differences were noted.     

Assembled dendritic titanium catalysts for enantioselective hetero-Diels-Alder reaction of aldehydes with Danishefsky's diene

A new type of dendritic 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN)-derived Schiff-base ligands have been synthesized and applied to the titanium-catalyzed hetero-Diels-Alder reaction of Danishefsky's diene with aldehydes. These reactions afforded the corresponding 2-substituted 2,3-dihydro-4H-pyran-4-ones in quantitative yields and with excellent enantioselectivities (up to 97.2 % ee). The disposition of the dendritic wedges and the dendron size in the ligands were found to have significant impact on the enantioselectivity of the reaction. The recovered dendritic catalyst could be reused without further addition of the Ti source or a carboxylic acid additive for at least three cycles, retaining similar activity and enantioselectivity. The high stability of this type of assembled dendritic titanium catalyst may be attributed to the stabilization effect of large-sized dendron units in the catalyst molecule. The other important phenomenon observed with this catalyst system is that a higher degree of asymmetric amplification has been achieved by attachment of the dendron unit to the chiral ligand, which represents a new advantage of dendrimer catalysts for asymmetric reactions using chiral ligands of lower optical purity.     

Enantioselective addition of alkynylzinc to arylaldehydes catalyzed by azetidino amino alcohols bearing an additional stereogenic center

Chiral azetidino amino alcohol ligands bearing an additional stereogenic center were readily prepared and used as catalysts for the asymmetric addition of alkynylzinc to aromatic aldehydes with enantioselectivities of up to 87% ee. The relationship between the reaction enantioselectivity and the structure of the chiral ligands was also evaluated in this reaction. The experimental results showed that the enantioselectivity level of the reaction was greatly influenced by the second stereogenic center attached to azetidine ring, but the stereochemical sense was only determined by the configuration of the azetidine ring. A possible transition structure for the catalytic asymmetric addition was also proposed.     

Ligand effects in aluminium-catalyzed asymmetric Baeyer-Villiger reactions

Asymmetric Baeyer-Villiger oxidations of racemic and prochiral cyclobutanones can be performed with chiral aluminium-based Lewis acids resulting in products with good enantioselectivities in high yields. By employing substituted BINOL derivatives as ligands, remarkable catalyst efficiencies have been achieved and γ-butyrolactones with up to 84% ee were obtained. The relation between the electronic properties of the ligand and the enantioselectivity of the reaction has been investigated, leading to a better understanding of the requirements for achieving a good enantioselectivity in this aluminium-catalyzed oxidative transformation.     

联萘酚衍生C_3对称的手性配体的合成及其在诱导二乙基锌与芳基醛的不对称加成反应中的应用

合成了一种新型可重复使用的含手性联萘酚的C3对称树状小分子配体(L1),并将L1用于诱导二乙基锌和芳基醛的不对称加成反应.获得的二级醇最高的对映选择性为91%ee,产物最高收率达99%.反应完成后,只需经过简单的萃取和洗涤过程就可实现对配体L1高回收率的回收.配体L1重复使用5次其催化活性和对映选择性没有明显变化.     

Highly efficient iridium catalyst for asymmetric transfer hydrogenation of aromatic ketones under base-free conditions

[reaction: see text] Catalytic systems generated in situ from the chiral PNNP ligands with iridium or rhodium hydride complexes exhibited excellent catalytic activity and good enantioselectivity in the asymmetric transfer hydrogenation of aromatic ketones without added base. The best result was obtained in the IrH(CO)(PPh(3))(3)-ligand 2 catalytic system with up to 99% yield and 97% ee.     

Highly enantioselective phenylacetylene additions to both aliphatic and aromatic aldehydes

The readily available and inexpensive BINOL in combination with Ti(O(i)Pr)(4) is found to catalyze the reaction of an alkynylzinc reagent with various types of aldehydes including aliphatic aldehydes, aromatic aldehydes, and other alpha,beta-unsaturated aldehydes to generate chiral propargyl alcohols with 91-99% ee at room temperature. No previous chiral catalysts have exhibited such a broad scope of enantioselectivity with respect to the type of aldehydes for this reaction. [reaction: see text]     

Self-supported BINOL-Zn catalysts for heterogeneous enantioselective epoxidation of (E)-α,β-unsaturated ketones

A class of chiral self-supported catalysts prepared from bis-BINOL ligands and diethyl zinc were successfully applied in the hetereogeneous enantioselective epoxidation of a range of (E)-α,β-unsaturated ketones, affording the corresponding epoxy ketones in high enantioselectivity. The self-supported catalysts were easily recovered from the reaction mixture and were reusable for several consecutive runs.     

Synthesis of chiral iridium complexes immobilized on amphiphilic polymers and their application to asymmetric catalysis

This article details the enantioselective catalytic performance of crosslinked, polymer immobilized, Ir‐based, chiral complexes for transfer hydrogenation of cyclic imines to chiral amines. Polymerization of the achiral vinyl monomer, divinylbenzene, and a polymerizable chiral 1,2‐diamine monosulfonamide ligand followed by complexation with [IrCl₂Cp*]₂ affords the crosslinked polymeric chiral complex, which can be successfully applied to asymmetric transfer hydrogenation of cyclic imines. Polymeric catalysts prepared from amphiphilic achiral monomers have high catalytic activity in the reaction and can be used both in organic solvents and water to give chiral cyclic amines with a high level of enantioselectivity (up to 98% ee). The asymmetric reaction allows for reuse of the heterogeneous catalyst without any loss in activity or enantioselectivity over several runs. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3037–3044     

The synthesis of dendritic BINOL ligands and their applications in the enantioselective Lewis acid catalyzed addition of diethylzinc to aldehydes

Novel dendritic chiral BINOL ligands have been synthesized through coupling of MOM-protected 3,3′-dihydroxymethyl-binaphthol with Fréchet-type polyether benzyl bromide dendrons followed by deprotection of the MOM groups using TsOH. These dendritic chiral BINOL ligands were found to be effective in the enantioselective addition of diethylzinc to benzaldehyde both in the presence and absence of Ti(O-iso-Pr)₄. The enantioselectivity decreased with increasing generation in both cases. In the latter case, the dendritic chiral BINOL ligands showed much higher catalytic activity and enantioselectivity than BINOL.     

Asymmetric Diels—Alder Reaction Catalyzed by Novel Chiral Dibenzo[a,c] cycloheptadiene Bis（oxazoline） Metal Complexes

A series of novel chiral C2-symmetric bis (oxazoline) ligands have been synthesized.The copper and magnesium complexes,prepared in situ from copper(Ⅱ)-triflate of magnesium triflate with the new enantiopure oxazoline ligands,were evaluated as chiral catalysts in the enantioselective Diels-Alder reaction of cyclopentadiene with N-crotenoyl-oxazolidin-2-one.Primary results showed that diastereoselectivity up to 94% and enantioselectivity up to 68% ee for endo products were observed respectively with these ligands.     

Enantioselective Iron‐Catalyzed Intramolecular Cyclopropanation Reactions

An iron‐catalyzed asymmetric intramolecular cyclopropanation was realized in high yields and excellent enantioselectivity (up to 97 % ee) by using the iron complexes of chiral spiro‐bisoxazoline ligands as catalysts. The superiority of iron catalysts exhibited in this reaction demonstrated the potential abilities of this sustainable metal in asymmetric carbenoid transformation reactions.     

Chiral 2,6-bis(oxazolinyl)pyridine-rare earth metal complexes as catalysts for highly enantioselective 1,3-dipolar cycloaddition reactions of 2-benzopyrylium-4-olates

Significant levels of enantioselectivity were obtained in 1,3-dipolar cycloadditions of 2-benzopyrylium-4-olate generated from the Rh(2)(OAc)(4)-catalyzed decomposition of o-methoxycarbonyl-alpha-diazoacetophenone. This reaction utilized chiral 2,6-bis(oxazolinyl)pyridine (Pybox)--rare earth metal triflate complexes as chiral Lewis acid catalysts. The reactions with several benzyloxyacetaldehyde derivatives catalyzed by a Sc(III)--Pybox-i-Pr complex (10 mol %) proceeded smoothly to yield endo-adducts selectively with high enantioselectivity (up to 93% ee). For the reaction with benzyl pyruvate, the Sc(III)-Pybox-i-Pr complex (10 mol %) catalyzed the reaction effectively in the presence of trifluoroacetic acid (10 mol %) to yield an exo-adduct with both high diastereo- and enantioselectivity (94% ee). This catalytic system was efficiently applied to the reactions with several other alpha-keto esters with high exo- and enantioselectivities (up to 95% ee). In contrast to the reaction with carbonyl compounds, Yb(III)--Pybox-Ph complex (10 mol %) was found to be effective to obtain high enantioselectivity (96% ee) of diastereoselectively produced exo-cycloadduct in the reaction with 3-acryloyl-2-oxazolidinone.     

A highly enantioselective hetero-Diels-Alder reaction of aldehydes with Danishefsky's diene catalyzed by chiral titanium(IV) 5,5',6,6',7,7',8,8'-octahydro-1,1'-bi-2-naphthol complexes

The catalytic effect of chiral Lewis acids on the hetero-Diels-Alder reaction between aldehydes and Danishefsky's diene (1) has been investigated. A variety of combinations of different ligands and Lewis acids have been examined as catalysts for the hetero-Diels-Alder reaction between benzaldehyde and 1, and it has been found that the readily accessible Ti(IV)-H(8)-BINOL (TiHBOL) complex is a very effective catalyst for the reaction, leading to products with very high enantioselectivity (up to 99% ee) and yield (92%). The hetero-Diels-Alder reaction of other aldehydes with 1 under the catalysis of TiHBOL is a general reaction which proceeds well with very high enantioselectivity and isolated yield for various aldehydes at 0 degrees C to room temperature. Based on the experimental results, the proposed mechanism of the hetero-Diels-Alder reaction and the dihedral angle effects of ligands are discussed.     

Asymmetric Michael reaction promoted by new chiral phase-transfer catalysts

A catalytic asymmetric Michael reaction promoted by new chiral quaternary ammonium salts is described. The products are obtained with moderate ee (up to 75% ee), and the enantioselectivity is strongly dependent on both the substituents on the aromatic rings and the ammonium moiety in the catalysts.     

手性自负载催化剂研究新进展

催化剂的负载和回收再利用是提高其使用效率、降低反应成本和减少金属离子对产物污染的一条有效途径。与传统的负载模式不同, 手性自负载催化剂通过含双或多官能团的手性配体与金属通过自组装形成一类有机-无机聚合物,因此无需使用任何载体,即能够有效地实现手性催化剂的回收和再利用。近年来,手性自负载催化剂作为一种新的负载模式,已经成功地应用于一些非均相催化的不对称反应中。本文概述了手性自负载催化剂的在一些不对称催化反应研究中取得的新进展。     

Enantioselective turnover in glyoxylate-ene reactions catalyzed by chiral copper complexes

The catalytic, enantioselective carbonyl-ene reaction of ethyl glyoxylate with α-methylstyrene and 4-halo-α-methylstyrene has been investigated in the presence of copper triflate-bisoxazoline complexes. The reaction proceeded smoothly to give γ,δ-unsaturated-α-hydroxy esters in moderate to good yields and with excellent enantioselectivity (up to 100% ee). A hypothesis has been provided to explain the reversal of enantioselectivity in the reaction.