Self-assembly of bidentate ligands for combinatorial homogeneous catalysis: asymmetric rhodium-catalyzed hydrogenation

The first chiral ligand library based on self-assembly through complementary hydrogen-bonding was realized. From a 10 x 4 ligand library, catalysts that show excellent activity and enantioselectivity for the asymmetric rhodium-catalyzed hydrogenation have been identified.     

Chiral bidentate aminophosphine ligands: synthesis, coordination chemistry and asymmetric catalysis

Chiral aminophosphines Ph2PN(R)(CH2)nN(R)PPh2 1-4 [n= 2, R = CH(CH3)(Ph) 1; n= 3, R = CH(CH2CH3)(Ph) 2, n= 2, R = CH(CH3)(1-naphthyl) 3; n= 2, R = CH(CH3)(C6H11) 4] were synthesized by the reaction of ClPPh2 with the appropriate easily accessible enantiopure amine building blocks. For compounds 1 and 2, the corresponding selenides 5 and 6 were prepared to determine the electronic character of the phosphine moieties. By reaction of 1 with either PdCl2(cod) or PdCl(CH3)(cod) the cis-complexes 7 and 8 were obtained. The molecular structure for complex 7, cis-[PdCl2(1)], was determined by X-ray crystallography. Reaction of PtCl2(cod) with 1 or 2 yielded the corresponding monomeric cis-isomers 9 and 10. The rhodium derivative [RhCl(CO)(1)] (11) was obtained as a mixture of cis and trans-isomers. Preliminary results in the rhodium catalyzed hydroformylation of styrene and vinyl acetate, with ee's up to 51% and high regioselectivities, showed the potential of these chiral aminophosphines for homogeneous catalysis.     

Polysiloxane-bound ligand accelerated catalysis: a modular approach to heterogeneous and homogeneous macromolecular asymmetric dihydroxylation ligands

Polysiloxane acts as a modular scaffold for macromolecular reagent development. Two separate components were covalently integrated into one material, one constituent provided reagent functionality, the other modulated solubility. In particular cinchona alkaloid based ligands used in the osmium tetroxide catalyzed asymmetric dihydroxylation (AD) reaction were covalently attached to commercially available polysiloxane. To enhance the reactivity of these polymeric ligands, multifunctional reagents were designed to include both the cinchona alkaloid and an alkoxyethylester solubilizing moiety providing random co-polymers. While the mono-functional materials led to heterogeneous conditions, the bi-functional polymers resulted in homogeneous reaction mixtures. Although both reagent types provided diol products with excellent yield and selectivity (>99% ee in nearly quantitative yield) the homogeneous analog has nearly twice the reactivity. Every repeat unit in the heterogeneous material was functionalized along the polysiloxane backbone while approximately half of these sites contained ligand in the homogeneous version. This approach led to macromolecular catalysts with high loadings of ligand and therefore materials with very low equivalent weights. Although these polymers are highly loaded they do maintain reactivity on a par with their free ligand counterpart. Using straightforward purification techniques (i.e. precipitation, simple filtration, or ultrafiltration) these polymeric ligands were easily separated from diol product and reused multiple times. Polysiloxane is a viable support for the catalysis of AD reactions and may provide a generally useful backbone for other catalytic systems.     

UREAphos: supramolecular bidentate ligands for asymmetric hydrogenation

Supramolecular bidentate phosphite ligands are presented as a new class of ligands for rhodium catalysed asymmetric hydrogenation.     

C1 and C2-symmetric carbohydrate phosphorus ligands in asymmetric catalysis

Carbohydrates are increasingly used as starting materials for the synthesis of enantiopure ligands. They contain a considerable number of stereocenters, and compounds with all possible configurational combinations are readily available. This tutorial review focuses on ligands obtained by the introduction of phosphorus functionalities (mainly phosphinite, phosphite or phosphine) into a carbohydrate framework. They are classified according to their structural features. In this review, ligands are organised as C1 ligands with a pyranoside or furanoside structure, and C2 ligands. Particular attention is paid to water soluble ligands prepared from carbohydrates. General methods for the preparation of the ligands are presented in order to show how the backbones can be obtained from simple carbohydrates. The catalytic results obtained in commonly studied processes are presented in tables in order to facilitate the comparison between the ligands. The advantages and limitations of the use of ligands based on carbohydrates are discussed.     

Concepts for ligand design in asymmetric catalysis: a study of chiral amino thiol ligands

A series of new chiral sulfur–nitrogen chelate ligands, derived from amino acids, has been synthesised rationally. Fruitless experiments into catalytic asymmetric conjugate additions and desymmetrisation of meso-epoxides led us to analyse our ligands in the catalytic asymmetric addition of diethylzinc to aromatic aldehydes. These latter experiments were successful with chiral benzylic alcohols being obtained in up to 82% enantiomeric excess.     

P-Chirogenic diaminophosphine oxide: a new class of chiral phosphorus ligands for asymmetric catalysis

We successfully synthesized a novel P-chirogenic diaminophosphine oxide 4, which was applied to catalytic enantioselective construction of quaternary carbon centers using Pd-catalyzed asymmetric allylic substitution with various beta-keto esters (up to 99% yield, 94% ee). Preliminary mechanistic studies indicated that two molecules of 8 coordinate to the Pd metal in a monodentate fashion, resulting in the formation of Pd complex 9 (Pd:8 = 1:2), which functions as the active species.     

A modular approach to structurally diverse bidentate chelate ligands for transition metal catalysis

A modular approach to a new class of structurally diverse bidentate P/N, P/P, P/S, and P/Se chelate ligands has been developed. Starting from hydroquinone, various ligands were synthesized in a divergent manner via orthogonally bis-protected bromohydroquinones as the central building block. The first donor functionality (L1) is introduced to the aromatic (hydroquinone) ligand backbone either by Pd-catalyzed cross-coupling (Suzuki coupling) with hetero-aryl bromides, by Pd-catalyzed amination, or by lithiation and subsequent treatment with electrophiles (e.g., chlorophosphanes, disulfides, diselenides, or carbamoyl chlorides). After selective deprotection, the second ligand tooth (L2) is attached by reaction of the phenolic OH functionality with a chlorophosphane, a chlorophosphite, or a related reagent. Some of the resulting chelate ligands were converted into the respective PdX2 complexes (X = Cl, I), two of which were characterized by X-ray crystallography. The methodology developed opens an access to a broad variety of new chiral and achiral transition metal complexes and is generally suited for the solid-phase synthesis of combinatorial libraries, as will be reported separately.     

手性胺膦配体在不对称催化中的应用

利用邻二苯基膦苯甲醛分别与多种手性二胺的缩合反应,设计合成了一系列新型手性四齿胺膦配体.这类多齿胺膦配体含有两个软的磷原子和两个硬的氮原子,具有丰富的配位化学性能和优秀的不对称诱导能力.本文综述了手性胺膦金属络合物催化剂在不对称转移氢化反应、氧化动力学拆分反应、烯烃的不对称环氧化反应和不对称环丙烷化反应、不对称D-A反应中的应用.     

Chiral phosphine-phosphoramidite ligands in asymmetric catalysis

Chiral phosphine-phosphoramidite ligands, featuring ready availability, easy modification, and stability towards air and moisture, have recently emerged as a new kind of robust ligands for asymmetric catalysis. They have been found to display wide utilities in various catalytic asymmetric reactions, giving excellent enantioselectivities in the Rh-, Ru-, and Ir-catalyzed asymmetric hydrogenation of C?C, C?O, and C?N double bonds; Rh-catalyzed asymmetric hydroformylation; Pd-catalyzed asymmetric hydrophosphorylation; Pd-catalyzed asymmetric allylic alkylation; Ag-catalyzed asymmetric [3 + 2] cycloaddition; and Cu-catalyzed conjugate addition and reduction. In this review, the progress on the development of chiral phosphine-phosphoramidite ligands in asymmetric catalysis has been summarized.     

Supramolecular bidentate ligands by metal-directed in situ formation of antiparallel beta-sheet structures and application in asymmetric catalysis

The principles of protein structure design, molecular recognition, and supramolecular and combinatorial chemistry have been applied to develop a convergent metal-ion-assisted self-assembly approach that is a very simple and effective method for the de novo design and the construction of topologically predetermined antiparallel beta-sheet structures and self-assembled catalysts. A new concept of in situ generation of bidentate P-ligands for transition-metal catalysis, in which two complementary, monodentate, peptide-based ligands are brought together by employing peptide secondary structure motif as constructing tool to direct the self-assembly process, is achieved through formation of stable beta-sheet motifs and subsequent control of selectivity. The supramolecular structures were studied by (1)H, (31)P, and (13)C NMR spectroscopy, ESI mass spectrometry, X-ray structure analysis, and theoretical calculations. Our initial catalysis results confirm the close relationship between the self-assembled sheet conformations and the catalytic activity of these metallopeptides in the asymmetric rhodium-catalyzed hydroformylation. Good catalyst activity and moderate enantioselectivity were observed for the selected combination of catalyst and substrate, but most importantly the concept of this new methodology was successfully proven. This work presents a perspective interface between protein design and supramolecular catalysis for the design of beta-sheet mimetics and screening of libraries of self-organizing supramolecular catalysts.     

Chiral fluorous phosphorus ligands based on the binaphthyl skeleton: synthesis and applications in asymmetric catalysis

Two enantiopure fluorous phosphines have been conveniently synthesized by combining palladium-catalyzed coupling reactions of easily available binaphthyl building-blocks with the introduction of fluorous ponytails onto aromatic compounds via ether bond formation. These new fluorous chiral phosphines have been tested as ligands in metal-catalyzed asymmetric transformations, the best results being obtained in the palladium-catalyzed asymmetric allylic substitution of 1,3-diphenyl-2-propenyl acetate affording the products of up to 87% e.e.     

New phosphorus dendrimers with chiral ferrocenyl phosphine-thioether ligands on the periphery for asymmetric catalysis

Chiral ferrocenyl phosphine-thioether ligands have been covalently bound on the periphery of 4 phosphorus dendrimers (generations 1-4) having a cyclotriphosphazene core and on one model compound. These new dendrimers proved to be efficient ligands for the palladium-catalyzed asymmetric allylic substitution reaction (ee up to 93%).     

P-alkene bidentate ligands: an unusual ligand effect in Pd-catalysed Suzuki reactions

The versatile reagent bis(diphenylphosphino)benzaldehyde was used to prepare a variety of electronically and sterically varied ligands using Wittig or aldol methodology in high yields. Pd-catalysed Suzuki reactions were evaluated using these ligands. The influence of the functional group on the alkene, which is in direct conjugation with the phosphorus centre of the ligand, was visible in the activity profiles of the reactions. In general, the activity and stability of the Pd-ligand system increased as electron deficiency and steric bulk increased at the alkene. Furthermore, the ligands could be used at decreased catalyst loadings with improved yields and did not themselves participate in the reactions as substrates.     

PipPhos and MorfPhos: privileged monodentate phosphoramidite ligands for rhodium-catalyzed asymmetric hydrogenation

A library of 20 monodentate phosphoramidite ligands has been prepared and applied in rhodium-catalyzed asymmetric hydrogenation. This resulted in the identification of two ligands, PipPhos and MorfPhos, that afford excellent and in several cases unprecedented enantioselectivities in the hydrogenation of N-acyldehydroamino acid esters, dimethyl itaconate, acyclic N-acylenamides, and cyclic N-acylenamides. In addition, a method for the parallel enantioselectivity determination of eight acylated amines is presented.