Synthesis of chiral 1,3-bis(1-(diarylphosphoryl)ethyl)-benzenes via Ir-catalyzed double asymmetric hydrogenation of bis(diarylvinylphosphine oxides)

<正>1 General methods Unless otherwise noted, all reactions and manipulations involving air- or moisture-sensitive compounds were performed using standard Schlenk techniques or in a glovebox. All solvents were purified and dried using standard procedures. Melting points were measured on a RY-I apparatus and uncorrected. 1H, 13 C, 31 P and 19 F NMR spectra were recorded on Varian Mercury 300 or 400 MHz spectrometers. Chemical shifts(δ values) were reported in ppm downfield from internal TMS(1H NMR), CDCl3(13C NMR), external 85% H3PO4(31P NMR), and external CF3CO2H(19F NMR), respectively. Optical rotations were determined using a Perkin Elmer 341 MC polarimeter. The IR spectra were measured on a BRUKER TENSOR 27     

Chiral diphosphines and diphosphinites derived from 2,2-biphosphole: Stereodynamic ligands for asymmetric catalysis

In this account, the recent advances on chiral stereochemically dynamic 2,2’-biphosphole ligands for applications in asymmetric catalysis are reported. In the first part, the synthesis of stereodynamic diphosphines and diphosphinites derived from 2,2’-biphosphole is presented. The second part describes the kinetic dynamic resolution to give diastereo- and enantiopure complexes. Applications in asymmetric allylic substitution, hydroformylation and hydrogenation are presented in the last part.     

铱-氮膦配体催化剂在非官能化烯烃不对称氢化中的研究

非官能化烯烃的不对称氢化反应一直是烯烃加氢领域的难点。研究表明,铱-氮膦配体催化剂对此类反应具有很好的催化活性和选择性,因而受到国内外众多学者的关注。本文对近年来利用铱-氮膦配体催化剂对非官能化烯烃进行不对称氢化的研究进展进行了综述,介绍了不对称氢化的历程及背景,着重讨论了铱-氮膦配体催化剂的催化机理（Ir^Ⅲ-Ir^Ⅴ催化循环机理、Ir^Ⅰ-Ir^Ⅲ催化循环机理）、铱催化剂的组成以及催化性能的比较,并对铱催化剂在不对称氢化中的发展前景作了展望。     

Application of phosphine-oxazoline ligands in Ir-catalyzed asymmetric hydrogenation of acyclic aromatic N-arylimines

[reaction: see text] A new class of chiral phosphine-oxazoline ligands have been developed. Chiral Ir complexes prepared from these ligands induced high enantioselectivities (66-90% ee) when applied to the asymmetric hydrogenation of acyclic aromatic N-arylimines.     

Diastereo‐ and Enantioselective anti‐Selective Hydrogenation of α‐Amino‐β‐keto Ester Hydrochlorides and Related Compounds Using Transition‐Metal–Chiral‐Bisphosphine Catalysts

This review describes our recent works on the diastereo‐ and enantioselective synthesis of anti‐β‐hydroxy‐α‐amino acid esters using transition‐metal–chiral‐bisphosphine catalysts. A variety of transition metals, namely ruthenium (Ru), rhodium (Rh),iridium (Ir), and nickel (Ni), in combination with chiral bisphosphines, worked well as catalysts for the direct anti‐selective asymmetric hydrogenation of α‐amino‐β‐keto ester hydrochlorides, yielding anti‐β‐hydroxy‐α‐amino acid esters via dynamic kinetic resolution (DKR) in excellent yields and diastereo‐ and enantioselectivities. The Ru‐catalyzed asymmetric hydrogenation of α‐amino‐β‐ketoesters via DKR is the first example of generating anti‐β‐hydroxy‐α‐amino acids. Complexes of iridium and axially chiral bisphosphines catalyze an efficient asymmetric hydrogenation of α‐amino‐β‐keto ester hydrochlorides via dynamic kinetic resolution. A homogeneous Ni–chiral‐bisphosphine complex also catalyzes an efficient asymmetric hydrogenation of α‐amino‐β‐keto ester hydrochlorides in an anti‐selective manner. As a related process, the asymmetric hydrogenation of the configurationally stable substituted α‐aminoketones using a Ni catalyst via DKR is also described.     

Control of the mutual arrangement of cyclometalated ligands in cationic iridium(III) complexes. Synthesis, spectroscopy, and electroluminescence of the different isomers

Synthetic control of the mutual arrangement of the cyclometalated ligands (C^N) in Ir(III) dimers, [Ir(C^N)(2)Cl](2), and cationic bis-cyclometalated Ir(III) complexes, [Ir(C^N)(2)(L^L)](+) (L^L = neutral ligand), is described for the first time. Using 1-benzyl-4-(2,4-difluorophenyl)-1H-1,2,3-triazole (HdfptrBz) as a cyclometalating ligand, two different Ir(III) dimers, [Ir(dfptrBz)(2)Cl](2), are synthesized depending on the reaction conditions. At 80 °C, the dimer with an unusual mutual cis-C,C and cis-N,N configuration of the C^N ligands is isolated. In contrast, at higher temperature (140 °C), the geometrical isomer with the common cis-C,C and trans-N,N arrangement of the C^N ligand is obtained. In both cases, an asymmetric bridge, formed by a chloro ligand and two adjacent nitrogens of the triazole ring of one of the cyclometalated ligands, is observed. The dimers are cleaved in coordinating solvents to give the solvento complexes [Ir(dfptrBz)(2)Cl(S)] (S = DMSO or acetonitrile), which maintain the C^N arrangement of the parent dimers. Controlling the C^N ligand arrangement in the dimers allows for the preparation of the first example of geometrical isomers of a cationic bis-cyclometalated Ir(III) complex. Thus, N,N-trans-[Ir(dfptrBz)(2)(dmbpy)](+) (dmbpy = 4,4'-dimethyl-2,2'-bipyridine), with cis-C,C and trans-N,N arrangement of the C^N ligands, as well as N,N-cis-[Ir(dfptrBz)(2)(dmbpy)](+), with cis-C,C and cis-N,N C^N ligand orientation, are synthesized and characterized. Interestingly, both isomers show significantly different photophysical and electroluminescent properties, depending on the mutual arrangement of the C^N ligands. Furthermore, quantum chemical calculations give insight into the observed photophysical experimental data.     

Synthesis of antidepressant duloxetine via asymmetric transfer hydrogenation

Antidepressant duloxetine （1） was prepared via asymmetric transfer hydrogenation of 3-（dimethylamino）-1-（thiophen-2- yl）propan-1-one （3）. The Ru（Ⅱ）, Rh（Ⅲ） and Ir（Ⅲ） complexes of several chiral ligands were examined as the catalyst and （S,S）-N-tosyl-1,2-diphenyl ethylenediamine （TsDPEN）-Ru（Ⅱ） complex was found to provide good yield and excellent enantioselectivity. 2007 Ming Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Highly enantioselective asymmetric hydrogenation of (E)-β,β-disubstituted α,β-unsaturated Weinreb amides catalyzed by Ir(I) complexes of SpinPhox ligands

The Ir(I) complexes of chiral spiro phosphino-oxazoline ligands (SpinPhox) have demonstrated good to excellent enantioselectivity in the asymmetric hydrogenation (AH) of a variety of (E)-β,β-disubstituted α,β-unsaturated N-methoxy-N-methylamides, affording the corresponding optically active Weinreb amides with up to 97% ee.     

Asymmetric Transfer and Pressure Hydrogenation with Earth‐Abundant Transition Metal Catalysts

The asymmetric transfer and pressure hydrogenation of various unsaturated substrates provides a succinct pathway to important chiral intermediates and products such as chiral alcohols, amines, and alkanes. The use of earth‐abundant transition metals such as Fe, Co, Ni, and Cu in hydrogenation reactions provides an attractive alternative to traditionally used metals such as Ru, Rh, Ir, and Pd because they are comparatively inexpensive, less toxic, and as their name suggests, more abundant in nature. Earth‐abundant transition metal‐catalyzed asymmetric hydrogenation is rapidly becoming an important area of research. This review summarizes advances in the asymmetric hydrogenation of unsaturated bonds (ketones, imines, and alkenes) with earth‐abundant transition metals.     

Synthesis of tunable bisphosphine ligands and their application in asymmetric hydrogenation of quinolines

A series of tunable axial chiral bisphosphine ligands have been synthesized from (S)-MeO-Biphep. The Ir complex of the MeO-PEG-supported ligand (S)-4k has been successfully applied in asymmetric hydrogenation of quinolines with up to 92% ee. The catalyst system is air-stable and recyclable.     

过渡金属/磷配体催化不对称氢化反应研究进展

正手性过渡金属配合物催化的不对称氢化是合成手性药物、农药和精细化工中间体的重要方法.到目前为止,已经有一些过渡金属/配体配合物催化的不对称氢化反应得到工业化应用,典型的实例如孟山都公司采用手性双齿膦配体DIPAMP生产L     

C-H activations at iridium(I) square-planar complexes promoted by a fifth ligand

In the presence of ligands such as acetonitrile, ethylene, or propylene, the Ir(I) complex [Ir(1,2,5,6-eta-C8H12)(NCMe)(PMe3)]BF4 (1) transforms into the Ir(III) derivatives [Ir(1-kappa-4,5,6-eta-C8H12)(NCMe)(L)(PMe3)]BF4 (L = NCMe, 2; eta2-C2H4, 3; eta2-C3H6, 4), respectively, through a sequence of C-H oxidative addition and insertion elementary steps. The rate of this transformation depends on the nature of L and, in the case of NCMe, the pseudo-first-order rate constants display a dependence upon ligand concentration suggesting the formation of five-coordinate reaction intermediates. A similar reaction between 1 and vinyl acetate affords the Ir(III) complex [Ir(1-kappa-4,5,6-eta-C8H12){kappa-O-eta2-OC(Me)OC2H3}(PMe3)]BF4 (7) via the isolable five-coordinate Ir(I) compound [Ir(1,2,5,6-eta-C8H12){kappa-O-eta2-OC(Me)OC2H3}(PMe3)]BF4 (6). DFT (B3LYP) calculations in model complexes show that reactions initiated by acetonitrile or ethylene five-coordinate adducts involve C-H oxidative addition transition states of lower energy than that found in the absence of these ligands. Key species in these ligand-assisted transformations are the distorted (nonsquare-planar) intermediates preceding the intramolecular C-H oxidative addition step, which are generated after release of one cyclooctadiene double bond from the five-coordinate species. The feasibility of this mechanism is also investigated for complexes [IrCl(L)(PiPr3)2] (L = eta2-C2H4, 27; eta2-C3H6, 28). In the presence of NCMe, these complexes afford the C-H activation products [IrClH(CH=CHR)(NCMe)(PiPr3)2] (R = H, 29; Me, 30) via the common cyclometalated intermediate [IrClH{kappa-P,C-P(iPr)2CH(CH3)CH2}(NCMe)(PiPr3)] (31). The most effective C-H oxidative addition mechanism seems to involve three-coordinate intermediates generated by photochemical release of the alkene ligand. However, in the absence of light, the reaction rates display dependences upon NCMe concentration again indicating the intermediacy of five-coordinate acetonitrile adducts.     

含有手性BINAP基团的共轭微孔聚合材料应用于喹啉高效不对称氢化反应

喹啉不对称氢化反应是不对称氢化研究的重点之一。其氢化产物四氢喹啉不仅是重要的有机合成中间体,同时也是自然界中生物碱的结构单元和生物活性化合物。周永贵研究组首次报道了手性(R)-MeO-Biphep/Ir体系成功用于喹啉的不对称催化,取得了非常好的反应结果。随后他们对喹啉底物进行了拓展,包括拥有特殊取代基的喹啉衍生物,均取得了良好的反应结果。后来多个研究组对该反应进行了深入研究并开发出了多个不同手性膦配体的Ir催化体系。虽然喹啉不对称氢化反应取得了很大的发展,但是该均相反应体系只能在高的反应催化剂用量下才能实现好的结果。进一步研究发现手性配体与金属Ir络合后形成反应活性物种,但后者可发生二聚或三聚,生成的产物是不具有催化活性的,从而导致了反应体系需要高的催化剂的用量。为此人们做了大量研究。范青华研究组通过对BINAP基团上嫁接大空间位阻的枝状分子合成了一系列新的手性BINAP配体,在与Ir络合后,表现出远高于均相催化剂的反应活性,且可循环利用。在该体系中,大位阻的枝状分子起到了阻隔活性物种二聚、三聚的作用,因而提高了反应活性。后来周永贵研究组也尝试通过改变有机配体的方法来实现高的反应活性。他们选择改变手性双膦配体上P原子所连接有机配体的空间位阻来实现对活性物种多聚的控制。实验同样取得了很好的反应效果。对于均相反应体系,我们只能通过这种改变有机配体空间位阻的方式来降低活性物种多聚的可能性,那么如何彻底阻止这种多聚呢？非均相体系给我们提供了很好的研究思路,但如何将非均相体系引入到喹啉不对称氢化反应体系当中成为了难点。
　　共轭微孔聚合物(CMPs)的发展使得手性催化体系很容易从均相转变到非均相。这种材料具有较高的比表面积和固定的开放孔道结构,可应用于非均相催化中。且制备相对容易。我们可以将手性双膦配体作为材料制备配体嫁接到CMPs材料当中。在这种材料当中,手性配体会以有序、空间分离的方式分布,在与Ir配合后应用于喹啉不对称氢化反应中,从而从根本上避免了活性物种多聚的可能因此反应活性提高。我们曾首次成功合成了一系列含有手性(R)-Binap基团的共轭微孔聚合材料-BINAP-CMPs,并将其用于β-酮酸酯的不对称氢化反应当中,取得了很好的催化效果。手性BINAP基团均匀、有序地分散于该材料中。我们尝试利用BINAP-CMPs固有的空间隔离效应,将其应用于喹啉的不对称氢化反应中,结果表明,在相同条件下,非均相BINAP-CMPs/Ir催化体系的TOF值是340 h–1,是均相BINAP/Ir体系(100 h–1)3倍,反应的对映体选择性与均相相当;另外该催化体系多循环利用次后仍可以保持高的反应活性。我们还发现材料结构性质对反应结果的影响很大,材料的比表面积和孔容更大反应结果更好。     

Lysosome‐targeted Cyclometalated Iridium (III) Anticancer Complexes Bearing Phosphine‐Sulfonate Ligands

The synthesis, characterization and biological activity of four cyclometalated Ir (III) complexes ( Ir1 ‐ Ir4 ) containing different phosphine‐sulfonate ligands are reported. Most of these complexes showed good activity against A549 cancer cell lines and the human HeLa cervical cell lines. Spectroscopic properties study displays that all four complexes show rich fluorescence with emission maxima in the range of 474–510 nm. Fluorescence property of these complexes provides a tool to investigate the microscopic mechanism by confocal microscopy. Notably, the typical Ir (III) complex Ir4 can specially localize to lysosome, damage it and induce cell death via apoptosis. In addition, Ir4 enters into A549 cancer cells dominantly through energy‐dependent pathway.     

BINOL-derived phosphoramidites in asymmetric hydrogenation: can the presence of a functionality in the amino group influence the catalytic outcome?

In discovering the remarkable catalytic properties of BINOL-derived phosphoramidites (binoP-NR(2)), Dutch researchers recently achieved a long-awaited breakthrough in asymmetric catalysis. For the first time, easily accessible monodentate chiral P(III) ligands turned out to provide high enantioselectivities when used in rhodium-catalysed olefin hydrogenation. The simplest ligand representative of this family is MonoPhos, which can be made straightforwardly from BINOL and hexamethylphosphorous triamide. Since the first publication dealing with such catalysts (J. Am. Chem. Soc., 2000), a variety of binoP-NRR' ligands have been reported in which the amino group bears a functional substituent or a stereogenic centre. This critical review examines the impact of the presence of such a functionality in the amino group on catalytic olefin hydrogenation reactions.     

Chiral iridium(I) bis(NHC) complexes as catalysts for asymmetric transfer hydrogenation

The common use of NHC complexes in transition‐metal mediated C–C coupling and metathesis reactions in recent decades has established N‐heterocyclic carbenes as a new class of ligand for catalysis. The field of asymmetric catalysis with complexes bearing NHC‐containing chiral ligands is dominated by mixed carbene/oxazoline or carbene/phosphane chelating ligands. In contrast, applications of complexes with chiral, chelating bis(NHC) ligands are rare. In the present work new chiral iridium(I) bis(NHC) complexes and their application in the asymmetric transfer hydrogenation of ketones are described. A series of chiral bis(azolium) salts have been prepared following a synthetic pathway, starting from L ‐valinol and the modular buildup allows the structural variation of the ligand precursors. The iridium complexes were formed via a one‐pot transmetallation procedure. The prepared complexes were applied as catalysts in the asymmetric transfer hydrogenation of various prochiral ketones, affording the corresponding chiral alcohols in high yields and moderate to good enantioselectivities of up to 68%. The enantioselectivities of the catalysts were strongly affected by the various, terminal N‐substituents of the chelating bis(NHC) ligands. The results presented in this work indicate the potential of bis‐carbenes as stereodirecting ligands for asymmetric catalysis and are offering a base for further developments. Copyright © 2010 John Wiley & Sons, Ltd.     

金属催化的不对称氢化反应研究进展与展望

手性过渡金属络合物催化的不对称氢化反应是合成光学活性化合物的重要方法. 本文从手性配体及手性催化剂、不对称催化新反应、新方法和新策略三个方面简要评述新世纪以来过渡金属催化的不对称氢化反应研究领域的新进展. 从新世纪初至今, 手性单磷配体得到了复兴, 出现了如MonoPhos、SiPhos、DpenPhos等高效单齿亚磷酰胺酯配体; 磷原子手性(P-手性)配体也得到了快速发展, 如BenzP*、ZhanPhos、TriFer等已成为新的高效手性双膦配体; 螺环骨架手性配体成为新世纪手性配体设计合成的亮点, 除了SiPhos、SIPHOX、SpinPHOX等高效手性螺环配体外, 手性螺环吡啶胺基磷配体SpiroPAP的铱催化剂成为目前最高效的分子催化剂. 不对称催化氢化新反应研究也取得了突破, 如非保护烯胺、杂芳环化合物及N-H亚胺的氢化等反应都实现了高对映选择性. 自组装手性催化剂、树枝状手性催化剂、铁磁性纳米负载的可回收手性催化剂, 以及“混合”配体手性催化剂等新方法和新策略也在不对称催化氢化反应中得到了应用. 然而, 手性过渡金属络合物催化的不对称氢化研究仍然充满挑战, 也期待新的突破.     

Mechanism of the Asymmetric Hydrogenation of Exocyclic α,β‐Unsaturated Carbonyl Compounds with an Iridium/BiphPhox Catalyst: NMR and DFT Studies

The mechanism of the asymmetric hydrogenation of exocyclic α,β‐unsaturated carbonyl compounds with the (aS)‐Ir/iPr‐BiphPhox catalyst was studied by NMR experiments and DFT computational analyses. Computed optical yields of the asymmetric hydrogenation proceeding by an iridium(I)/iridium(III) mechanism involving a transition state stabilized through two intramolecular hydrogen bonds are in good accordance with the experimental ee values.     

Diphosphite ligands based on ribose backbone as suitable ligands in the hydrogenation and hydroformylation of prochiral olefins

Rh(I) and Ir(I) cationic complexes [M(cod)(PP)]BF₄ have been synthesised from diphosphite ligands 4–6 derived from ribofuranose. They have been used in the rhodium and iridium catalysed asymmetric hydrogenation of acrylic acid derivatives. Ribose derivative ligands 4–6 have also been used as auxiliaries in the Rh-catalysed hydroformylation of styrene. Hydroformylation results have been explained on the basis of the species formed under hydroformylation conditions. Comparative experiments with the related epimer d-(+)-xylose derivatives showed that the configuration of the product is controlled by the absolute configuration of the stereogenic carbon atom C-3.     

Synthesis of a new class of conformationally rigid phosphino-oxazolines: highly enantioselective ligands for Ir-catalyzed asymmetric hydrogenation

[reaction: see text] A new class of conformationally rigid phosphino-oxazoline ligands were synthesized from readily available enantiopure phenyl glycinol. Ir complexes with these ligands are air-stable and highly enantioselective catalysts for asymmetric hydrogenation of aryl alkenes and alpha,beta-unsaturated esters in up to 99% ee.