A highly efficient catalyst system based on ruthenium-pincer-type complexes has been discovered for N-formylation of various amines with CO2 and H2, thus affording the corresponding formamides with excellent productivity (turnover numbers of up to 1 940 000 in a single batch) and selectivity. Using a simple catalyst recycling protocol, the catalyst was reused for 12 runs in N,N-dimethylformamide production without significant loss of activity, thus demonstrating the potential for practical utilization of this cost-effective process. A one-pot two-step procedure for hydrogenation of CO2 to methanol via the intermediacy of formamide formation has also been developed.
A highly efficient catalyst system based on ruthenium-pincer-type complexes has been discovered for N-formylation of various amines with CO2 and H2, thus affording the corresponding formamides with excellent productivity (turnover numbers of up to 1 940 000 in a single batch) and selectivity. Using a simple catalyst recycling protocol, the catalyst was reused for 12 runs in N,N-dimethylformamide production without significant loss of activity, thus demonstrating the potential for practical utilization of this cost-effective process. A one-pot two-step procedure for hydrogenation of CO2 to methanol via the intermediacy of formamide formation has also been developed.
The first example of efficient asymmetric hydrogenation of challenging β-aryloxyacrylic acids was realized using a RhI-complex based on the heterocombination of a readily available chiral monodentate secondary phosphine oxide (SPO) and an achiral monodentate phosphine ligand as the catalyst. Excellent enantioselectivities (92–>99 % ee) were achieved for a wide variety of chiral β-aryloxypropionic acids with minor aryloxy elimination in most cases. The resultant products were readily transformed into biologically active compounds through simple synthetic manipulations.
No abstract is available for this article.
Optically active medium-sized cyclic carbonyl compounds bearing an α-chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/IrI catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the CC bonds in the exocyclic α,β-unsaturated cyclic carbonyls, including a broad range of α-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging α-alkylidenelactam substrates with six- or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an α-chiral carbon center in generally excellent enantiomeric excesses (up to 98 % ee). Synthetic utility of the protocol has also been demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen and its analogue, as well as biologically important ε-aminocaproic acid derivatives.
Optically active medium-sized cyclic carbonyl compounds bearing an α-chiral carbon center are of interest in pharmaceutical sciences and asymmetric synthesis. Herein, SpinPhox/IrI catalysts have been demonstrated to be highly enantioselective in the asymmetric hydrogenation of the CC bonds in the exocyclic α,β-unsaturated cyclic carbonyls, including a broad range of α-alkylidene lactams, unsaturated cyclic ketones, and lactones. It is noteworthy that the procedure can be successfully used in the asymmetric hydrogenation of the challenging α-alkylidenelactam substrates with six- or seven-membered rings, thus affording the corresponding optically active carbonyl compounds with an α-chiral carbon center in generally excellent enantiomeric excesses (up to 98 % ee). Synthetic utility of the protocol has also been demonstrated in the asymmetric synthesis of the anti-inflammatory drug loxoprofen and its analogue, as well as biologically important ε-aminocaproic acid derivatives.
The dinuclear magnesium complexes generated in situ from the reaction of chiral multidentate semi-azacrown ether ligands with n-Bu2Mg were found to be efficient catalysts for enantioselective ring-opening of meso-epoxides with aniline derivatives, affording the corresponding chiral β-amino alcohols in good yields with up to 90% ee.
The organometallic approach is one of the most active topics in catalysis. The application of NH functionality in organometallic catalysis has become an important and attractive concept in catalyst design. NH moieties in the modifiers of organometallic catalysts have been shown to have various beneficial functions in catalysis by molecular recognition through hydrogen bonding to give catalyst–substrate, ligand–ligand, ligand–catalyst, and catalyst–catalyst interactions. This Review summarizes recent progress in the development of the organometallic catalysts based on the concept of cooperative catalysis by focusing on the NH moiety.
Der metallorganische Ansatz ist eines der großen Themen auf dem Gebiet der Katalyse, und insbesondere die Nutzung von NH-Funktionen hat sich zu einem wichtigen und attraktiven Konzept für das Katalysator-Design entwickelt. NH-Einheiten in metallorganischen Katalysatoren zeigen diverse positive Effekte auf die Katalyse, vor allem durch molekulare Erkennung mittels Wasserstoffbrücken unter Ausbildung von Katalysator-Substrat-, Ligand-Ligand-, Ligand- Katalysator- und Katalysator-Katalysator-Wechselwirkungen. Dieser Aufsatz behandelt unter besonderer Berücksichtigung der NH-Gruppe die neuesten Fortschritte in der Entwicklung metallorganischer Katalysatoren basierend auf dem Konzept der kooperativen Katalyse.
The spiro-2,2′-bichroman-based chiral bisoxazoline ligands (SPANbox) were found to be highly efficient in copper(II)- and zinc(II)-catalyzed asymmetric chlorinations of cyclic β-keto esters with N-chlorosuccinimide (NCS) as the chlorination reagent, to give the corresponding α-chloro-β-keto esters in excellent yields in 5–30 min with ee values up to 97%. The copper(II) triflate and zinc(II) triflate complexes of a single SPANbox ligand demonstrated complementary results to each other with respect to the enantioselection, affording both antipodes of the chlorinated product enantiomers with good to excellent optical purities.
A new class of bidentate phosphoramidite ligands, based on a spiroketal backbone, has been developed for the rhodium-catalyzed hydroformylation reactions. A range of short- and long-chain olefins, were found amenable to the protocol, affording high catalytic activity and excellent regioselectivity for the linear aldehydes. Under the optimized reaction conditions, a turnover number (TON) of up to 2.3×104 and linear to branched ratio (l/b) of up to 174.4 were obtained in the RhI-catalyzed hydroformylation of terminal olefins. Remarkably, the catalysts were also found to be efficient in the isomerization–hydroformylation of some internal olefins, to regioselectively afford the linear aldehydes with TON values of up to 2.0×104 and l/b ratios in the range of 23.4–30.6. X-ray crystallographic analysis revealed the cis coordination of the ligand in the precatalyst [Rh(3 d)(acac)], whereas NMR and IR studies on the catalytically active hydride complex [HRh(CO)2(3 d)] suggested an eq–eq coordination of the ligand in the species.
A practical asymmetric synthesis of enantiopure spiro[4,4]nonane-1,6-dione, a valuable precursor for chiral ligand development, is reported. This synthetic strategy includes a kinetic resolution of the readily synthesized ketone precursor with a chiral quaternary carbon center by bioreduction with baker’s yeast as the key step, followed by a hydroformylation, oxidation, esterification and Dieckmann cyclization reaction sequence to generate the spiro five-membered ring. It was found that the masking of the β-ketone carbonyl group of enantiopure ethyl 1-allyl-2-oxocyclopentanecarboxylate via formation of a ketal with 1,3-diol derivative is necessary during the process of Dieckmann condensation in order to prevent its racemization under basic conditions. This method allows the gram-scale preparation of both enantiomers of spiro[4,4]nonane-1,6-dione (1) with excellent enantiopurities (up to >99% ee) in the overall yields of 54% [(R)-1] and 42% [(S)-1], respectively. The practicality of the present synthetic procedure has provided a fundamental platform for the development of spiro[4,4]nonane-1,6-dione-based chiral chemistry.
Catalytic asymmetric Baeyer–Villiger (B–V) oxidation of 2,3,4-trisubstituted cyclobutanone (4) has been realized by the catalysis of a 1,1′-bi-2-naphthol (BINOL)-derived chiral phosphoric acid (1j), which contains bulky 2,4,6-triisopropyl phenyl groups at the 3,3′-positions of the BINOL backbone, using 30 % aqueous H2O2 as the oxidant, affording the corresponding γ-lactone (5) in 99 % yield with 95 % ee. In a divergent kinetic resolution of racemic 2,3-disubstituted bicyclic cyclobutanones (6) through asymmetric B–V oxidation, the chiral phosphoric acid 1p demonstrated excellent catalytic performance, giving a range of regioisomeric chiral lactones in a normal lactone (nl)/abnormal lactone (al) ratio of up to 2.1:1, with up to 99 % ee in the al product. It was found that fine tuning of the stereoelectronic properties of the backbone in chiral phosphoric acids is critically important for attaining high levels of enantioselectivity in the catalysis of B–V reactions of different type of cyclobutanones. The present work has provided a convenient approach to the synthesis of a variety of optically active chiral γ-lactones.
Catalyzed by the Mg complexes of BINOL derivatives, the enantioselective ring opening reaction of various meso-epoxides proceeded smoothly with either aromatic or aliphatic amines as the nucleophiles to afford the corresponding chiral β-amino alcohols in moderate-to-high yields with good to excellent enantioselectivities.
The intermolecular charge-transfer effect has been employed for the first time as a modulating approach to affect the enantioselectivity in asymmetric catalysis by taking the chiral phosphoric acid catalyzed asymmetric Baeyer-Villiger oxidation of 3-aryl cyclobutanones as the reaction prototype. It was found that the electron acceptor additives were able to effectively tune the enantioselectivity via donor-acceptor interaction with the catalyst and up to 9% enhancement of ee value was observed in a favorable case.
The mechanism of the chiral phosphoric acid catalyzed Baeyer–Villiger (B–V) reaction of cyclobutanones with hydrogen peroxide was investigated by using a combination of experimental and theoretical methods. Of the two pathways that have been proposed for the present reaction, the pathway involving a peroxyphosphate intermediate is not viable. The reaction progress kinetic analysis indicates that the reaction is partially inhibited by the γ-lactone product. Initial rate measurements suggest that the reaction follows Michaelis–Menten-type kinetics consistent with a bifunctional mechanism in which the catalyst is actively involved in both carbonyl addition and the subsequent rearrangement steps through hydrogen-bonding interactions with the reactants or the intermediate. High-level quantum chemical calculations strongly support a two-step concerted mechanism in which the phosphoric acid activates the reactants or the intermediate in a synergistic manner through partial proton transfer. The catalyst simultaneously acts as a general acid, by increasing the electrophilicity of the carbonyl carbon, increases the nucleophilicity of hydrogen peroxide as a Lewis base in the addition step, and facilitates the dissociation of the OH group from the Criegee intermediate in the rearrangement step. The overall reaction is highly exothermic, and the rearrangement of the Criegee intermediate is the rate-determining step. The observed reactivity of this catalytic B–V reaction also results, in part, from the ring strain in cyclobutanones. The sense of chiral induction is rationalized by the analysis of the relative energies of the competing diastereomeric transition states, in which the steric repulsion between the 3-substituent of the cyclobutanone and the 3- and 3′-substituents of the catalyst, as well as the entropy and solvent effects, are found to be critically important.
α-Aminophosphonates are an important class of compounds with diverse and useful biological activities. Despite that their structues are similar to that of proline, however, chiral cyclic α-aminophosphonates have found little applications in catalytic asymmetric synthesis. In this paper, an enantiopure α-aminophosphonate has been synthesized and was found to be effective as a chiral organocatalyst for the asymmetric conjugate addition of cycloketones to β-nitrostyrenes. With a catalyst loading of 20 mol% and in the presence of 10 mol% of CF3COOH as a cocatalyst, the Michael adducts could be obtained with varying degrees of diastereo- and enantioselectivities (up to 97:3 and 90% ee respectively) under solvent-free conditions.
This Focus Review highlights the exciting results obtained in the area of asymmetric catalysis using spirobiindane- or spirobifluorene-based chiral ligands. The spiro, mono, and bidentate ligands have been successfully applied in a wide range of transition-metal-catalyzed asymmetric reactions, including hydrogenations, carbon–carbon and carbon–heteroatom coupling reactions, with superior or comparable enantioselectivities to those obtained by using the related ligands bearing other backbones, thus proving that the spiro skeleton is a type of privileged structure for chiral ligand design. It is expected that the spiro concept for chiral ligand design will stimulate the future efforts to understand the features that account for their broad applicability and to apply this understanding to seek new privileged chiral ligands and catalysts.
Well-designed, self-assembled, metal–organic frameworks were constructed by simple mixing of multitopic MonoPhos-based ligands (3; MonoPhos=chiral, monodentate phosphoramidites based on the 1,1′-bi-2-naphthol platform) and [Rh(cod)2]BF4 (cod=cycloocta-1,5-diene). This self-supporting strategy allowed for simple and efficient catalyst immobilization without the use of extra added support, giving well-characterized, insoluble (in toluene) polymeric materials (4). The resulting self-supported catalysts (4) showed outstanding catalytic performance for the asymmetric hydrogenation of a number of α-dehydroamino acids (5) and 2-aryl enamides (7) with enantiomeric excess (ee) ranges of 94–98 % and 90–98 %, respectively. The linker moiety in 4 influenced the reactivity significantly, albeit with slight impact on the enantioselectivity. Acquisition of reaction profiles under steady-state conditions showed 4 h and 4 i to have the highest reactivity (turnover frequency (TOF)=95 and 97 h−1 at 2 atm, respectively), whereas appropriate substrate/catalyst matching was needed for optimum chiral induction. The former was recycled 10 times without loss in ee (95–96 %), although a drop in TOF of approximately 20 % per cycle was observed. The estimation of effective catalytic sites in self-supported catalyst 4 e was also carried out by isolation and hydrogenation of catalyst–substrate complex, showing about 37 % of the RhI centers in the self-supported catalyst 4 e are accessible to substrate 5 c in the catalysis. A continuous flow reaction system using an activated C/4 h mixture as stationary-phase catalyst for the asymmetric hydrogenation of 5 b was developed and run continuously for a total of 144 h with >99 % conversion and 96–97 % enantioselectivity. The total Rh leaching in the product solution is 1.7 % of that in original catalyst 4 h.
An efficient catalytic enantioselective hetero-Diels–Alder reaction of Danishefsky's diene with aldehydes using the magnesium binaphthoxide system has been developed, affording a variety of 2-substituted 2,3-dihydro-4H-pyran-4-ones in high yields and with excellent ee values. The aggregation behavior and nonlinear effect of the catalytic system, as well as the remarkable stereoelectronic effects of ligands on the catalysis, have also been investigated. On the basis of the structure of the isolated reaction intermediate, the stereochemistry of the products, and the information attained from a study of the nonlinear effect, a plausible asymmetric induction model has been proposed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
We herein report on solution structural studies of RuII catalysts (3a, 9) composed of achiral bisphosphine ligands (4, 8) and the enantiopure 1,2-diphenylethylenediamine (DPEN). Complete chiral induction from enantiopure (R,R)-DPEN to achiral bisphosphine ligand 3a was observed in solution, with the complex adopting a single, stable and non-fluxional (even at 70 °C) configuration. The coordination of the CO moiety in 4 to the cationic RuII center is considered to be of key importance in providing the higher thermodynamic and kinetic rotation barrier for the flexible bisphosphine ligand in the complex. The obtained enantioselectivity (91% enantiomeric excess) and sense of chiral induction in the hydrogenation of acetophenone were found to be solely dependent on the chirality of the 1,2-diamine. Consistent with the hydrogenation product, the (R,R)-DPEN induces a M-conformation (right-handed) chirality for flexible phosphine ligand 4 in the complex, resulting in a λ,λ-configuration about the RuII center.
The programmed assembly strategy has been applied to the generation of self-supported Noyori-type catalysts for asymmetric hydrogenation of ketones by spontaneous hetero-coordination of an achiral bridged diphosphine and chiral bridged diamine ligands with RuII metal ions. The immobilized catalyst demonstrates good enantioselectivity and activity in the heterogeneous catalysis of the hydrogenation of aromatic ketones and can be recovered and recycled for 4 times without obvious loss of selectivity and activity.
A new class of low-cost and easy-to-prepare monodentate phosphoramidite ligands (CydamPhos) has been developed from readily accessible and cheap trans-1,2-diaminocyclohexane as starting material through a three-step transformation. This type of ligands exhibited excellent enantioseletivities and high activities in rhodium(I)-catalyzed asymmetric hydrogenations of dehydro-α-amino acid methyl esters 9 (ee: 96.2–99.8 %) and acetylenamides 11 (91.8–98.8 %). The remarkable substituent effects exhibited by the ligands on the enantioselective control of the catalysis are rationalized on the basis of molecular structure of the catalyst precursor.
We report the design and synthesis of a novel class of RuII catalysts (3) composed of achiral benzophenone-based bisphosphane ligands and enantiopure 1,2-diamines for the asymmetric hydrogenation of aryl ketones. The developed catalysts show excellent enantioselectivities (up to 97 % ee) and activities (up to S/C = 10,000) in the hydrogenation of a variety of aromatic ketones.Complete chiral induction from the enantiopure 1,2-diamine to the achiral bisphosphane ligand was observed. The coordination of the C=O moiety in 3 to the cationic RuII center is considered to be of key importance in providing a higher thermodynamic and kinetic rotation barrier for the flexible bisphosphane ligand, resulting in the preferential formation of only one diastereomer, and thus explaining the high enantioselectivity of the catalyst. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Noncovalent interactions are used to generate a polymeric supramolecular chiral catalyst (see picture). This heterogeneous catalyst, which is based on Feringa's MonoPhos/RhI system, is formed by orthogonal self-assembly of recognition motifs through hydrogen bonding and ligand-to-metal coordination interactions. It shows excellent asymmetric induction and reusability in the catalysis of the asymmetric hydrogenation of dehydro-α-amino acid and enamide derivatives.
A novel chiral C2-symmetric 1,4-diamine with multistereogenic centers at the backbone of the ligand has been synthesized from cheap natural product D-mannitol through multistep transformations. Its diimine derivative (3 a) was found to be highly effective for the enantioselective control of the copper-catalyzed asymmetric aziridination of olefin derivatives with PhINTs as the nitrene source, affording the corresponding N-sulfonylated azirindine derivatives in good to excellent yields with up to 99 % ee (ee=enantiomeric excess). The catalyst system discovered in the present work was also extended to a one-pot enantioselective aziridination by using sulfonamide/iodobenzene diacetate as the nitrene source. In this case, most reactions proceeded smoothly to give the corresponding products in moderate yields with good to excellent enantiomeric excesses (75–96 % ee).
The development of heterogeneous chiral catalysts for enantioselective reactions is highly desirable in order to overcome some drawbacks of homogeneous catalysts. Different from the conventional approaches by using various types of supports or biphasic systems for the recovery and reuse of homogeneous catalysts, a conceptually new strategy for heterogenization of homogeneous chiral catalysts, that is, a “self-supporting” approach, has been developed to use homochiral metal–organic coordination polymers generated by the self-assembly of chiral multitopic ligands with metal ions, and thus obviates the use of any support. In this concept article, the success of this “self-supporting” strategy will be exemplified in heterogeneous catalysis of asymmetric carbonyl–ene, sulfoxidation, epoxidation, and asymmetric hydrogenation reactions.
In the present work, we report on catalysis of the enantioselective hydrogenation of ketones with Ru(II) complexes composed of cheap achiral monodentate phosphine ligands in combination with an enantiopure 1,2-diamine, affording a variety of optically active secondary alcohols with high efficiency and enantioselectivity. The steric impact of achiral monophosphine ligands in Ru complexes was found to be a critical factor for the high enantioselectivity of the reaction. This finding throws some light on a long-standing challenge, the high cost of chiral bisphosphine ligands, associated with an industrial application of the asymmetric hydrogenation of ketones.
A new strategy for the heterogenization of chiral titanium complexes was developed by the in situ assembly of bridged multitopic BINOL ligands with [Ti(OiPr)4] without using a support. The assembled heterogeneous catalysts (self-supported) showed excellent enantioselectivity in both the carbonyl–ene reaction of α-methylstyrene with ethyl glyoxylate (up to 98 % ee) and the oxidation of sulfides (up to >99 % ee). The catalytic performance of these heterogeneous catalytic systems was comparable or even superior to that attained with their homogeneous counterparts. The spacers between the two BINOL units of the ligands in the assembled catalysts had significant impact on the enantioselectivity of the carbonyl–ene reaction. This demonstrates the importance of the supramolecular structures of the assemblies on their catalytic behavior. In the catalysis of sulfoxidation, the self-supported heterogeneous titanium catalysts were highly stable and could be readily recycled and reused for over one month (at least eight cycles) without significant loss of activity and enantioselectivity (up to >99.9 % ee). The features of these self-supported catalysts, such as facile preparation, robust chiral structure of solid-state catalysts, high density of the catalytically active units in the solids, as well as easy recovery and simple recycling, are particularly important in developing methods for the synthesis of optically active compounds in industrial processes.
Verbrückt: Ein heterogenisierter freitragender Binol/La-Shibasaki-Katalysator wurde durch die Reaktion multitoper Liganden mit La(OiPr)3 synthetisiert (siehe Bild). Der Katalysator zeigt eine hohe Aktivität und Enantioselektivität sowie Wiederverwendbarkeit bei der asymmetrischen Epoxidierung von α,β-ungesättigten Ketonen.
The intramolecular dinuclear zinc complexes generated in situ from the reaction of multidentate semi-azacrown ether ligands with Et2Zn, followed by treatment with an alcohol additive, were found to promote the copolymerization of CO2 and cyclohexene oxide (CHO) with completely alternating polycarbonate selectivity and high efficiency. With this type of novel initiator, the copolymerization could be accomplished under mild conditions at 1 atm pressure of CO2, which represents a significant advantage over most catalytic systems developed for this reaction so far. The copolymerization reaction was demonstrated to be a living process as a result of the narrow polydispersities and the linear increase in the molecular weight with conversion of CHO. In addition, the solid-state structure of the dinuclear zinc complex was characterized by X-ray crystal structural analysis and can be considered as a model of the active catalyst. On the basis of the various efforts made to understand the mechanisms of the catalytic reaction, including MALDI-TOF mass analysis of the copolymers' end-groups, the effect of alcohol additives on the catalysis and CO2 pressure on the conversion of CHO, as well as the kinetic data gained from in situ IR spectroscopy, a plausible catalytic cycle for the present reaction system is outlined. The copolymerization is initiated by the insertion of CO2 into the ZnOEt bond to afford a carbonate–ester-bridged complex. The dinuclear zinc structure of the catalyst remains intact throughout the copolymerization. The bridged zinc centers may have a synergistic effect on the copolymerization reaction; one zinc center could activate the epoxide through its coordination and the second zinc atom may be responsible for carbonate propagation by nucleophilic attack by the carbonate ester on the back side of the cis-epoxide ring to afford the carbonate. The mechanistic implication of this is particularly important for future research into the design of efficient and practical catalysts for the copolymerization of epoxides with CO2.
Supramolecular assemblies of (±)-2,2′-dihydroxy-1,1′-binaphthyl (BINOL, A), with aza donor molecules including 2,2′-bipyridine (B) and naphthodiazine (C), have been synthesized and characterized by single-crystal X-ray diffraction methods. Two inclusion complexes crystallize in the triclinic system with P-1 space group. In the inclusion complex between A and B, two molecules of A and two molecules of B are linked each other by intermolecular hydrogen bonds with two molecules of water as the bridges, forming a centrosymmetric dimer with formula of A2(H2O)2B2; while in the inclusion complex between A and C, the molecule C virtually acts as a bridge to link molecules A through intermolecular OH…N hydrogen bonds, forming a short-chain supramolecular block with a formula of A2'C3 Besides the hydrogen bonding interaction between the host and guest molecules, π-π stacking interactions also play an important role in the solid-state packing of these two inclusion complexes. The structural information disclosed on the complex between dihydroxy compound and aza hydrogen bond acceptors in this work would be particularly important for the rational design of supramolecular organic functional materials.
The first catalytic enantioselective hetero-Diels–Alder reaction between Brassard's diene and aldehydes has been achieved through hydrogen-bonding activation using TADDOL derivatives as catalysts to afford the corresponding δ-lactone derivatives in moderate-to-good yields and with high enantioselectivities (up to 91 % ee). The reactions can be carried out either under solvent-free conditions or in toluene. On the basis of the absolute configurations of the products and the hydrogen-bonding interaction pattern between TADDOL (α,α,α′,α′-tetraaryl-1,3-dioxolan-4,5-dimethanol) and the carbonyl group disclosed by X-ray diffraction analysis, a possible mechanism for the catalytic reaction has been proposed. To demonstrate the usefulness of the methodology, a natural product, (S)-(+)-dihydrokawain, has also been prepared in 50 % isolated yield and with 69 % enantioselectivity in one step starting from 3-phenylpropionaldehyde by using this methodology. Therefore, this catalytic system is one of the most direct approaches to the construction of δ-lactone units, which will make the methodology very attractive for the synthesis of a variety of biologically important compounds and natural products.
A highly efficient and practical optical resolution of anti head-to-head racemic coumarin dimer 7 has been achieved by molecular complexation with TADDOL, (−)-8, through a hydrogen bonding interaction to afford the corresponding two enantiomers, (−)- and (+)-7, in 70 and 75 % yields, respectively, with >99 % ee. Starting from enantiopure (−)-7, a new type of C2-symmetric bisphosphine ligand (S,S,S,S)-3 with a cyclobutane backbone has been synthesized in good yield by facile transformations. The asymmetric induction efficiency of these chiral bisphosphine ligands in Pd-catalyzed asymmetric allylic substitution reactions was evaluated. Under the experimental conditions, the allylic substitution products could be obtained in excellent yields (up to 99 %) and enantioselectivities (up to 98.9 % ee). By taking advantage of the high enantioselectivity of this catalytic reaction and the easily derivable carboxylate groups on the cyclobutane backbone of ligand (S,S,S,S)-3, a new type of analogous ligand (S,S,S,S)-4 as well as the MeO-PEG-supported soluble ligand (S,S,S,S)-5 (PEG=polyethylene glycol) have also been synthesized and utilized in asymmetric allylic substitution reactions. In particular, the MeO-PEG supported (S,S,S,S)-5 b had a synergistic effect on the enantioselectivity of the reaction compared with its nonsupported precursor (S,S,S,S)-4 c, affording the corresponding allylation products 14 a and 14 b with excellent enantioselectivities (94.6 and 97.2 % ee, respectively). Moreover, the Pd complex of (S,S,S,S)-5 b could easily be recovered and recycled several times without significant loss of enantioselectivity and activity in the allylic substitution reactions.
An efficient asymmetric catalyst relies on the successful combination of a large number of interrelated variables, including rational design, intuition, persistence, and good fortune—not all of which are necessarily well-understood; this renders such practice largely empirical. As a result, the possibility of using combinatorial chemistry methods in asymmetric catalysis research has been widely recognized to be highly desirable. In this account, we attempt to show the principle and application of combinatorial approach in the discovery of chiral catalysts for enantioselective reactions. The concept focuses on the strategy for the creation of a modular chiral catalyst library by two-component ligand modification of metal ions on the basis of molecular recognition and assembly. The self-assembled chiral catalyst with two different ligands indeed exhibited synergistic effects in terms of both enantioselectivity and activity in comparison with its corresponding homocombinations in many reactions. The examples described in this paper demonstrated the powerfulness of combinatorial approach for the discovery of novel chiral catalyst systems, particularly for the development of highly efficient, enantioselective, and practical catalysts for enantioselective reactions. We hope this concept will stimulate further work on the discovery of more highly efficient and enantioselective catalysts, as well as unexpected classes of catalysts or catalytic enantioselective reactions in the future with the help of a combinatorial chemistry approach.
A new type of dendritic NOBIN derived Schiff base ligands has been synthesized and applied to titanium catalyzed hetero-Diels-Alder reaction of Danishelfsky's diene and aldehydes, affording the corresponding 2-substituted 2,3-dihydro-4H-pyran-4-one in good yields and moderate enantioselectivities (up to 59.2% ee). It was found that the size of dendron attached to the tri-dentated ligands has slight impact on the enantioselectivity of the reaction and the second generation of dendritic ligand exhibited the best enantioselectivity.
Ein Glyoxylatester wurde mit einer Reihe von Olefinen unter nahezu lösungsmittelfreien Bedingungen in Gegenwart geringer Mengen eines chiralen Katalysators (0.1–0.01 Mol-%) in einer milden enantioselektiven Carbonyl-En-Reaktion umgesetzt. Die α-Hydroxyester entstehen in hohen Ausbeuten und mit ausgezeichneten Enantioselektivitäten [Gl. (1)].
Simply mixing the neat substrates and a small amount of the chiral catalyst (0.1–0.01 mol %) under nearly solvent-free conditions makes the enantioselective carbonyl-ene reaction of glyoxylate ester with a variety of olefins proceed smoothly to afford the corresponding α-hydroxy esters in high yields with excellent enantioselectivities [Eq. (1)].
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.
![Phosphine,1,1'-[(1R)-2,2',3,3'-tetrahydro-1,1'-spirobi[1H-indene]-7,7'-diyl]bis[1,1-diphenyl-(9CI)](/data/chemimg/1006900/917377-74-3.png)
![Phosphine,1,1'-[(1R)-2,2',3,3'-tetrahydro-1,1'-spirobi[1H-indene]-7,7'-diyl]bis[1,1-diphenyl-(9CI)](/data/chemimg/1006900/917377-74-3_b.png)
![Carbonylchlorohydrido[6-(di-t-butylphosphinomethyl)-2-(N,N-diethylaminomethyl)pyridine]ruthenium(II)](http://img.cochemist.com/ccimg/864000/863971-62-4.png)
![Carbonylchlorohydrido[6-(di-t-butylphosphinomethyl)-2-(N,N-diethylaminomethyl)pyridine]ruthenium(II)](http://img.cochemist.com/ccimg/864000/863971-62-4_b.png)
![Iridium,[2-[bis(1-methylethyl)phosphino-kP]-N-[2-[bis(1-methylethyl)phosphino-kP]ethyl]ethanamine-kN]chlorodihydro-, stereoisomer (9CI)](http://img.cochemist.com/ccimg/791700/791629-96-4.png)
![Iridium,[2-[bis(1-methylethyl)phosphino-kP]-N-[2-[bis(1-methylethyl)phosphino-kP]ethyl]ethanamine-kN]chlorodihydro-, stereoisomer (9CI)](http://img.cochemist.com/ccimg/791700/791629-96-4_b.png)
![Cyclopentanone, 2-[(4-bromophenyl)methylene]-, (2E)-](http://img.cochemist.com/ccimg/602200/602169-12-0.png)
![Cyclopentanone, 2-[(4-bromophenyl)methylene]-, (2E)-](http://img.cochemist.com/ccimg/602200/602169-12-0_b.png)
![(S)-2-(2-Fluoro-[1,1'-biphenyl]-4-yl)propanoic acid](http://img.cochemist.com/ccimg/51600/51543-39-6.png)
![(S)-2-(2-Fluoro-[1,1'-biphenyl]-4-yl)propanoic acid](http://img.cochemist.com/ccimg/51600/51543-39-6_b.png)
