Oxazoline Ligands Research Articles

Enantioselective reactions catalyzed by chiral pyridine 2,6-bis(5',5'-diphenyloxazoline)-metal complexes

A new class of tridentate pyridine-bis(oxazoline) ligand having gem-diphenyl groups at C5 of the oxazoline rings has been developed. Its metal complex exhibited high catalytic efficiency in asymmetric synthesis. We have shown that gem-diphenyl groups at C5 of the oxazoline rings are essential for getting high enantiomeric excess.

Development of Diphenylamine‐Linked Bis(imidazoline) Ligands and Their Application in Asymmetric Friedel–Crafts Alkylation of Indole Derivatives with Nitroalkenes

AbstractThe new diphenylamine‐linked bis(imidazoline) ligands were prepared through Kelly‐You’s imidazoline formation procedure mediated by Hendrickson’s reagent in good yields. The novel ligands were tested in the asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes. In most cases, good yields (up to 97%) and excellent enantioselectivities (up to 98%) can be achieved. The optimized bis(imidazoline) ligand with trans‐diphenyl substitution on the imidazoline ring gave better enantioselectivity than the corresponding bis(oxazoline) ligand.

Synthesis of tetrahydroisoquinoline (TIQ)–oxazoline ligands and their application in enantioselective Henry reactions

A novel family of eleven new tetrahydroisoquinoline (TIQ)–oxazoline intermediates and five corresponding copper(II) catalysts has been developed and applied to the catalytic asymmetric Henry reaction of various aldehydes with nitromethane to provide β-hydroxy nitroalkanes in high conversion (>99%). This paper describes the synthesis of the TIQ compounds from l-dihydroxyphenylalanine ( l-DOPA) as the starting material. The chiral ligands were complexed in situ with various transition metals such as Cu, Sc, Co, Zn, Ni and Mn and tested as a chiral catalyst for the Henry reaction. The reaction was optimized in terms of the metal, counter ion, solvent, temperature and over a range of substrates. The corresponding catalyst with copper(II) acetate and 2-propanol as the solvent provides the best enantioselectivities (up to 77% ee) of the corresponding nitroalcohol for 4-chlorobenzaldehyde.

Axially chiral phosphine–oxazoline ligands in the silver(I)-catalyzed asymmetric Mannich reaction of fluorinated aldimines with trimethylsiloxyfuran

Axially chiral phosphine–oxazoline ligand L7, prepared from ( S)-binol, was found to be a fairly effective chiral ligand in the silver(I)-catalyzed asymmetric Mannich reaction of fluorinated aldimines with trimethylsiloxyfuran to give the corresponding adducts in up to 99% yield, over 20:1 dr and 81% ee.

Immobilization of Diphenylamine‐Linked Bis(oxazoline) Ligands and Their Application in the Asymmetric Friedel–Crafts Alkylation of Indole Derivatives with Nitroalkenes

AbstractA diphenylamine‐linked bis(oxazoline) ligand with trans‐diphenyl substitution on the oxazoline rings has been immobilized onto one‐ to three‐generation Fréchet‐type dendrimers and a C3‐symmetric core structure. The catalytic activities and enantioselectivities of these new ligands were tested in the asymmetric Friedel–Crafts alkylation reactions of indole derivatives with nitroalkenes. The two types of immobilized ligands exhibited similar enantioselectivities and substrate compatibilities to the free ligand trans‐DPBO we reported previously. No dendrimer effect was observed in the kinetic investigation of the Fréchet‐type dendrimer‐immobilized ligands. The in situ recycling of the catalysts was also tested to illustrate the effect of reducing catalyst loading and the efficiency of our system.

Asymmetric Kumada Couplings of α-Bromo Ketones

Kumada reactions (metal-catalyzed couplings of organic electrophiles with Grignard reagents) were among the first studied cross-­coupling reactions. Despite the early success of Kumada reactions with alkyl electrophiles, no examples of the enantioselective version have been reported. The authors described a novel asymmetric Kumada coupling of racemic α-bromo ­ketones with aryl Grignard reagents. The scope of the reaction is quite broad, exploiting Knochel’s methods for synthesizing functionalized Grignard reagents. High yields and ee values can be obtained, even with dialkyl ketones using modified bis(oxazoline) ligand 2. Furthermore, the cross-coupling products can be derivatized with good diastereoselectivity without racemization.

Direct Experimental Evidence for the Priority of Flexible Ligand Skeleton in Asymmetric Friedel-Crafts Alkylation of Indole with Nitroalkenes

Abstract: Direct experimental evidence for the priority of flexible ligand skeleton in asymmetric Friedel-Crafts alkylation was obtained through XRD analysis of flexible ligand/ZnCl 2 complex, as well as synthesis of dihydroacridine-linked bis(oxazoline) ligands with planar rigid scaffold. A transition state model without NH …  interaction was proposed for the rigid ligands to interpret the inversion of absolute configuration. Keywords: Rigid scaffold, flexible scaffold, diphenylamine, dihydroacridine, bis(oxazoline), Friedel-Crafts alkylation. INTRODUCTION Since the pioneering reports on oxazolines [1], chiral bis(oxazoline) ligands have been extensively developed by chemists in the fields of coordination chemistry, synthetic chemistry, and catalysis [2]. Large number of ligands with diverse scaffolds have been synthesized from commercially available amino alcohols and carboxylic acids/aldehydes through facile procedures, which illustrates their great potency in application. Some ligand scaffolds stand out from vast reports and gain broad applications in different asymmetric transformations [3], while most ligand scaffolds give satisfying results only in specific cases. Such a situation makes the design of novel ligands for designated reactions a difficult and unprofitable work. In recent years, some groups dedicated to the research on the relationship of ligand structure and enantioselectivity, especially the tuning of electronic effect and rigidity of ligand scaffold. Compared with the encouraging results achieved in the former case [4], much less attention has been paid on the tuning of rigidity [5]. Herein, we would like to document our recent progress on this subject. Diphenylamine-linked bis(oxazoline) ligands

Heterogeneous asymmetric Henry reaction using a chiral bis(oxazoline)-copper complex immobilized on magnetically separable mesocellular mesoporous silica support

A chiral bis(oxazoline) ligand was immobilized onto a magnetically separable hierarchically-ordered mesocellular mesoporous silica (M-HMMS) and this new catalytic system was examined in the asymmetric Henry reaction between various aldehydes and nitromethane at ambient temperature. Good enantioselectivity (upto 86.0% ee) was observed when the free silanol groups of the mesoporous silica were capped by trimethylsilyl group. This catalyst was separated magnetically and reused several times without significant loss of reactivity or enantioselectivity. This magnetic separation of catalysts could lead to further development toward practical industrial scale application due to simplicity without cumbersome filtration.

Copper-Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles

Friedel-Crafts alkylation of indole derivatives with α,β-unsaturated carbonyl compounds has been extensively developed due to the importance of indoles as building blocks in natural products and pharmaceutical agents. Despite the many contributions already in the literature, challenges still remain in developing highly efficient chiral catalysts for the Friedel-Crafts alkylation between indole and alkylidenemalonate. The authors reported the studies of hetero­arylidenemalonate-derived bis(oxazoline) ligands, such as 1, and their copper(II) complexes in the highly efficient and enantioselective Friedel-Crafts alkylation of indoles and alkylidenemalonates.

Rational tuning of the rigidity of a ligand scaffold: synthesis of diphenylsulfide-linked bis(oxazoline) ligands and their application in asymmetric allylic alkylation

The scaffold rigidity of bis(oxazoline) ligands was rationally tuned on the basis of literature information. Diphenylsulfide-linked bis(oxazoline) ligands with a flexible scaffold were efficiently synthesized to test our hypothesis. The improved enantioselectivity in palladium-catalyzed asymmetric allylic alkylation reaction was achieved as we expected.

Cyclopalladized complexes on the matrix of phenyland naphthyl-derivatives of oxazole and oxazoline with ethylenediamine

In the present work the results on synthesis and study of spectral properties are presented of the cyclopalladized complexes [Pd(C^N)En]ClO4 on the basis of oxazole and oxazoline derivatives [(C^N), deprotonated forms of 2-phenyl-2-oxazoline (pho), 2,5-diphenyloxazole (dpo), 2-(1-naphthyl)-5-phenyloxazole (npo), 2-phenylbenzoxazole (bo); En is 1,2diaminoethane]. The results of Н NMR (CD3CN) and IR (KBr) spectroscopy confirm the composition of complexes obtained in solution and in solid phase. The cyclopalladization leads not only to the deprotonation of phenyl and naphthyl substituents of oxazole and oxazoline ligands, but to the magnetic nonequivalence of amine protons of ethylenediamine due to the difference in the trans-effect of the donor atoms N and С of cyclometallated ligand. The IR spectra of complexes are characterized by both low-frequency shift of the stretching С=N vibrations of heterocyclic ligand and characteristic [4–6] change in the out-of-plane bending С–Н vibrations as a result of metallation of phenyl or naphthyl groups. DOI: 10.1134/S1070363210020337

Efficient Regio- and Stereoselective Formation of Azocan-2-ones via 8-Endo Cyclization of α-Carbamoyl Radicals

The iodine-atom-transfer 8-endo cyclization of alpha-carbamoyl radicals was investigated experimentally and theoretically. With the aid of Mg(ClO(4))(2) and a bis(oxazoline) ligand, N-ethoxycarbonyl-substituted N-(pent-4-enyl)-2-iodoalkanamides underwent 8-endo cyclization leading to the formation of only the corresponding 3,5-trans-substituted azocan-2-ones in excellent yields. Similarly, the BF(3).OEt(2)/H(2)O-promoted reactions of N-ethoxycarbonyl-N-(2-allylaryl)-2-iodoalkanamides afforded exclusively the benzazocanone products with a 3,5-cis configuration in high yields. The bidentate chelation of substrate radicals not only significantly improved the efficiency of cyclization but also resulted in the change of stereochemistry of azocanone products from 3,8-trans to 3,8-cis. Theoretical calculations at the UB3LYP/6-31G* level revealed that the cyclization of N-carbonyl-substituted alpha-carbamoyl radicals occurs via the E-conformational transition states without the presence of a Lewis acid. On the other hand, the cyclization proceeds via the Z-conformational transition states when the substrates form the bidentate chelation with a Lewis acid. In both cases, the 8-endo cyclization is always fundamentally preferred over the corresponding 7-exo cyclization. The complexed radicals having the more rigid conformations also allow the better stereochemical control in the iodine-atom-abstraction step. To further understand the reactivity of alpha-carbamoyl radicals, the competition between the 8-endo and 5-exo cyclization was also studied. The results demonstrated that the 8-endo cyclization is of comparable rate to the corresponding 5-exo cyclization for alpha-carbamoyl radicals with fixed Z-conformational transition states. As a comparison, the 8-endo mode is fundamentally preferred over the 5-exo mode in the cyclization of NH-amide substrates because the latter requires the Z-conformational transition states, whereas the former proceeds via the more stable E-conformational transition states.

ChemInform Abstract: New Thiazoline—Oxazoline Ligands and Their Application in the Asymmetric Friedel—Crafts Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective Fujiwara–Moritani Indole and Pyrrole Annulations Catalyzed by Chiral Palladium(II)–NicOx Complexes

AbstractThe catalytic asymmetric Fujiwara–Moritani ring closures of several indole‐ and pyrrole‐based cyclization precursors are reported. These unprecedented oxidative palladium(II)‐catalyzed annulations allow for the formation of a stereogenic quaternary carbon atom, and decent levels of enantiocontrol are seen in 5‐exo‐trig cyclizations (54 % ee for an indole and 76 % ee for a pyrrole) while 6‐exo‐trig ring closures afford essentially racemic material. Novel oxazoline ligands with a nicotine platform (NicOx) are pivotal for good catalytic turnover as conventional PyOx ligands failed to produce acceptable chemical yields. The preparation of these NicOx ligands as well as the syntheses of the cyclization precursors are described in detail.

Highly Enantioselective Friedel–Crafts Reaction of Indole with Alkylidenemalonates Catalyzed by Heteroarylidene Malonate‐Derived Bis(oxazoline) Copper(II) Complexes

AbstractA series of cheap and easily accessible heteroarylidenemalonate‐derived bis(oxazoline) ligands 1 and 2 were synthesized and their copper(II) complexes were applied to the catalytic Friedel–Crafts reaction between indoles and diethyl alkylidenemalonates, Excellent asymmetric enantioselectivities were afforded for the S‐enantiomer (up to >99% ee) in isobutyl alcohol, and the R‐enantiomer (up to 96.5% ee) in dichloromethane.

Asymmetric intramolecular Pd(II)-catalysed amidocarbonylation of unsaturated amino alcohols

The first example of an asymmetric carbonylative bicyclisation of racemic N-protected 1-amino-pent-4-ene-3-ols (±) -1 catalysed by palladium(II) with chiral bis(oxazoline) ligands was investigated. The kinetic resolution of (±) -1 in the presence of chiral catalyst, p-benzoquinone in acetic acid under carbon monoxide atmosphere afforded enantiomerically enriched derivatives of 2-oxa-6-azabicyclo[3.3.0]octan-3-ones ( R, R) -2 and ( S, S) -2, respectively.

First Regio‐ and Enantioselective Chromium‐Catalyzed Homoallenylation of Aldehydes

Game, set, and match: The first regio- and enantioselective version of the title reaction is described. The chiral catalyst prepared in situ from CrCl3 and a non-C2-symmetric bis(oxazoline) ligand 1 affords the valuable chiral β-allenols regioselectively in good yields with excellent ee values. R=aryl, alkyl.

Asymmetric [2,3]‐Wittig Rearrangement of Oxygenated Allyl Benzyl Ethers in the Presence of a Chiral di‐tBu‐bis(oxazoline) Ligand: A Novel Synthetic Approach to THF Lignans

We have accomplished highly enantioselective [2,3]-Wittig rearrangements of functionalized allyl benzyl ethers in the presence of a chiral di-tBu-bis(oxazoline) ligand. In various oxygenated benzylic ethers, the reactions proceeded with excellent diastereo- and enantioselectivities, although the presence of a methoxy substituent at the ortho-position on the benzyl group drastically decreased the enantioselectivity. Conversely, o-ethyl and o-phenyl substituents had no significant effect on the selectivity. We found that the C2-substituent of the allylic moiety played an important role in producing high enantioselectivity. Highly enantioselective [2,3]-Wittig rearrangement in the presence of catalytic amounts of the chiral ligands is also described.

New Thiazoline–Oxazoline Ligands and Their Application in the Asymmetric Friedel–Crafts Reaction

AbstractSix members of a novel non‐C2‐symmetric ligand class incorporating an oxazoline and thiazoline unit have been prepared in a four‐step, high‐yielding and convergent synthesis, in which the key step is a microwave‐assisted palladium‐catalyzed aryl amination. The new ligands induced enantiomeric excesses of up to 76 % in the asymmetric Friedel–Crafts reaction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Examination of the Role of Taft-Type Steric Parameters in Asymmetric Catalysis

We report the use of Taft steric parameters to correlate the substituent size of a ligand with the enantiomeric ratio of a reaction. Linear free energy relationships can be constructed by plotting the log of enantiomeric ratio (er) versus the steric parameters reported by Taft and modified by Charton. Successful correlations were found for aldehyde and ketone allylation under NHK conditions using modular oxazoline ligands developed in our laboratory. Using these correlations, ligands were designed and evaluated for carbonyl allylation reactions. A break in the Charton plot results and is attributed to a global structural change in the catalyst. Additionally, several previously reported enantioselective reactions are analyzed resulting in excellent correlations for both catalysts and substrates. Finally, limitations and issues are presented with illustrative examples.