Bis Oxazoline Research Articles

Iron(II)-Catalyzed Asymmetric Intramolecular Aminohydroxylation of Indoles

An enantioselective intramolecular indole aminohydroxylation reaction is catalyzed by iron(II)-chiral bisoxazoline (BOX) complexes (ee up to 99%, dr > 20:1). This discovery enables expedient asymmetric synthesis of a series of biologically active 3-amino oxindoles and 3-amino indolanes.

Asymmetric benzoylation of hydrobenzoin by copper(ii) bis(oxazoline) anchored onto ordered mesoporous silicas and their carbon replicas

A copper(II) complex with a commercial chiral bis(oxazoline) was anchored onto ordered mesoporous silica materials and their respective carbon replicas. The amount of transition metal complex loaded onto the mesostructured solids was determined by ICP-AES and the materials were also characterized by elemental analysis, FTIR, TG/DSC and isotherms of N2 adsorption at −196 °C. For the first time the asymmetric benzoylation of a 1,2-diol was performed in the heterogeneous phase by using an anchored commercial bis(oxazoline) ligand. The effect of the type of mesoporous material on the catalytic parameters, as well as on the reutilization of catalysts in several catalytic cycles, was checked. All the composites prepared were active, selective and enantioselective in this asymmetric organic transformation. Using the two ordered mesoporous silicas as supports good selectivities, with comparable yields and TONs to the homogeneous phase reaction, were obtained. Furthermore these two heterogeneous catalysts are more stable upon reuse than the corresponding ordered carbon replica materials. One of the former heterogeneous catalysts, with mesoporous silica as a support, could be further reused for 4 consecutive cycles without significant loss of selectivity, the TON or enantioselectivity.

ChemInform Abstract: Asymmetric Friedel—Crafts Alkylation of Indoles with Nitrodienes and 2‐Propargyloxy‐β‐nitrostyrenes Catalyzed by Diphenylamine‐Linked Bis(oxazoline)—Zn(OTf)2 Complexes.

The catalytic asymmetric Friedel–Crafts reaction of indoles with nitrodienes and 2-propargyloxy-β-nitrostyrenes was systematically investigated with diphenylamine-linked bis(oxazoline)–Zn(OTf)2 complexes. Moderate to good enantioselectivities were obtained with both kinds of substrates (up to 89 % ee for nitrodienes and up to 93 % ee for β-nitrostyrene derivatives). Further transformation of the corresponding Friedel–Crafts alkylation product of indole with 2-propargyloxy-β-nitrostyrene was carried out to give the chiral isoxazolobenzoxepane derivative, which is of medicinal chemistry interest, with retained enantiomeric purity.

New Application Progress of Chiral Bis(oxazoline) Ligands in Asymmetric Catalysis

The recent progress of bis(oxazoline) ligands applications in asymmetric catalysis is reviewed, in particular the

A Reusable TNF-Tagged Chiral Bis(oxazoline)-Copper Catalyst for Diels- Alder Transformations

A chiral bis(oxazoline) ligand, substituted on the methylene bridge by a covalent link to an electron-deficient moiety (2,4,7-trinitrofluoren-9-one, TNF), is a useful ligand associated to copper(II) salts to promote enantioselective Diels–Alder reactions between N-acyloxazolidinones and cyclopentadiene. Owing to different solubility properties, the corresponding catalyst was precipitated by pentane addition after reaction completion and was easily recovered by filtration. It was successfully reused in up to 20 successive catalytic cycles for the formation of the targeted products with no loss of either the activity or the enantioselectivity along with the recycling.

Identification and characterization of intermediates in the formation of the cyclobutadiene linked dimeric cobalt sandwich compound [( ${\eta ^{5}}$ -RCp)Co( ${\eta^{4}}$ -C 4 Ph 3 )] 2 [R ${=}$ H, CH 3 C(O)O

The synthesis of novel cyclobutadiene linked dimers of [η 5-RCp]Co(η 4-C4Ph4) was reported recently from a three-component reaction of 1,4-diphenylbutadiyne, diphenylacetylene and [η 5-RCp]Co(PPh3)2 [R = H or MeOC(O)]. The chiral bis oxazoline derivative of this dimer was found to form cobalt oxazolinyl palladacycles which were excellent chiral catalysts for the Overman–Claisen rearrangement of trichloroacetimidates, similar to the well-known COP catalysts. In this paper, we report reactions carried out for identifying the intermediates in the formation of the dimeric sandwich compound {[η 5-MeOC(O)Cp]Co(η 4-C4Ph3)}2 (1). On varying the stoichiometric ratio of the reactants of the three component reaction, two new cobalt sandwich compounds [η 5-MeOC(O)Cp]Co[η 4-C4Ph3(C≡CPh)] (2) and [η 5-MeOC(O)Cp]Co[η 4-C4-Ph2(C≡CPh)2] (3) were found to form as viscous oily liquids. The identity of 2 was ascertained by oxidizing its alkyne moiety to yield crystalline [η 5-MeOC(O)Cp]Co{η 4-C4Ph3[C(O)-C(O)Ph]} (4) which was structurally characterized. Further, the role of phenylethynyl derived monomeric sandwich compound 2 as a precursor to the dimeric compound 1 was established by reacting 2 with diphenylacetylene and CpCo(COD) which yielded the first example of an unsymmetrical cyclobutadiene linked dimeric cobalt sandwich compound {η 5-[MeOC(O)Cp]Co(η 4-C4Ph3)}[(η 5-Cp)Co(η 4-C4Ph3)] (5) which was also structurally characterized. The mechanism of the formation of cyclobutadiene linked dimers of the cobalt sandwich compound (η5-Cp)Co(η4-C4Ph4) has been studied. Two intermediates [η5-MeOC(O)Cp]Co[η4-C4Ph3(C≡CPh)] and [η5-MeOC(O)Cp]Co[η4-C4Ph2(C≡CPh)2] were isolated. The identity of the former was proved by oxidizing its alkyne moiety. Further, this compound was converted to a novel unsymmetrical cyclobutadiene linked dimer {η5-[MeOC(O)Cp]Co(η4-C4Ph3)} [(η5-Cp)Co(η4-C4Ph3)].

Recycling Chiral Copper Bis(oxazoline) Complexes in an Original Multireaction Procedure

Recycling Chiral Copper Bis(oxazoline) Complexes in an Original Multireaction Procedure

A facile and efficient synthesis of bis(oxazoline)s

Abstract magnified image Thiophene‐2,5‐dicarboxylic acid, benzene‐1,3‐dicarboxylic acid, or furan‐2,5‐di‐carboxylic acid, respectively, reacted with various β‐amino alcohols in toluene under reflux within 24 h, to form nine bis(oxazoline)s (1, 1a, 1b, 1c, 1d, 1e, 2, 2a, 2b, 2c, 3) in good yields through water deprivation via a one‐pot reaction. The synthetic method is facile and efficient and deserves great application potentials in the research and development in the area of bis(oxazoline)s. J. Heterocyclic Chem., (2010).

ChemInform Abstract: 4-Naphthyl-Substituted Bis(oxazoline): A New, Easily Recoverable and Efficient Chiral Ligand in Asymmetric Catalysis of the Diels-Alder Reaction.

Abstract 2, 2-Bis{2-[(4R)-(2′-naphthyl)-1, 3-oxazolinyl]}propane and its (4S) enantiomer were prepared starting from 2-vinylnaphthalene, following the Sharpless protocol, and were found to be optically pure (ee ≥ 99.5%) by hplc analysis. These new bis(oxazolines) are efficient chiral ligands in the asymmetric catalysis of the Diels-Alder reaction ofN-alkenoyl-oxazolidin-2-one derivatives since endo cycloadducts are obtained with up to 94% ee. Different Lewis acids were tested, the best one being the Mg(II) cation derived from the corresponding triflate. A remarkable feature of such new chiral ligands is the low solubility in polar solvents, so that the chiral ligand can be easily recovered by a simple filtration. The recovered ligand can be directly reused in other asymmetric syntheses, without any further purification and, overall, without any drop in the induced enantioselectivities. New chiral bis(oxazolines) were prepared starting from 2-vinylnaphthalene, and were shown to be efficient chiral ligands in the asymmetric catalysis of the Diels-Alder reaction of N-alkenoyl-oxazolidin-2-one derivatives: complexes built on magnesium triflate the endo cycloadducts to be obtained with up to 94% ee. A remarkable feature of such new chiral ligands is the low solubility in polar solvents allowing an easy recovery of the bis(oxazoline) in 75% yield by a simple filtration Download : Download full-size image .

ChemInform Abstract: The Addition Patterns of C60 Trisadducts Involving the Positional Relationships e and trans-n (n = 2-4): Isolation, Properties, and Determination of the Absolute Configuration of Tris(malonates) and Tris[bis(oxazolines)

A series of regioisomeric trisadducts of C60 (5–11, 14–18) having the positional relationships e and trans-n (n = 2–4) resulting from successive additions of malonates or bis(oxazolines) to [6,6]-double bonds of the fullerene framework has been isolated and characterized. The new adducts 8–11 and 15–17 represent examples of unprecedented addition patterns. The addition patterns of the new trisadducts with C2, Cs or C1 symmetry have been assigned on the basis of the known positional relationships of the addends in their precursor bisadducts, and those of the C2- or Cs-symmetric representatives have been verified by analysis of their NMR spectra. The absolute configurations of the adducts with inherently chiral addition patterns could be determined either by comparison of the calculated and experimental CD spectra of the bis(oxazoline) adducts or with knowledge of the absolute configurations of the chiral bisadduct precursors containing bis(oxazoline) addends. The CD spectra of the pairs of diastereomers with an enantiomeric addition pattern fA-15/fC-15, fA-16/fC-16, and fA-18/fC-18 show mirror image behavior and pronounced Cotton effects.

ChemInform Abstract: Chiral Bis(oxazoline) Copper(II) Complexes: Versatile Catalysts for Enantioselective Cycloaddition, Aldol, Michael, and Carbonyl Ene Reactions

A bis(oxazoline) (box) copper(II) complex and its hydrated counterpart (1 and 2) function as enantioselective Lewis acid catalysts for carbocyclic and hetero Diels−Alder, aldol, Michael, ene, and amination reactions with substrates capable of chelation through six- and five-membered rings. X-ray crystallography of the chiral complexes reveals a propensity for the formation of distorted square planar or square pyramidal geometries. The sense of asymmetric induction is identical for all the processes catalyzed by [Cu((S,S)-t-Bu-box)](X)2 complexes 1 and 2 (X = OTf and SbF) resulting from the intervention of a distorted square planar catalyst-substrate binary complex. These catalyzed processes exhibit excellent temperature−selectivity profiles. Reactions catalyzed by [Cu(S,S-Ph-pybox)](SbF6)2 and their derived chelation complexes are also discussed.

Preparation, structure and catalytic activity of copper(II) complexes of novel 4,4′-BOX ligands

This Letter details the synthesis of two new 4,4′-bisoxazoline (BOX) ligands. The copper(II) complex of one of the new ligands is structurally determined. The catalytic performance of the copper(II) complexes of the novel ligands, and that of our recently described phenyl AraBOX ligand in Diels–Alder reactions are reported. We have used the structural information to propose an explanation of a curious variation in the diastereoselectivity obtained in the case of one ligand complex.

The Synthesis of AraBOX, a New 4,4′-Bis(oxazoline), from Novel Pentitol-Derived Bis-β-amino Alcohols

The preparation of a novel phenyl 4,4'-bis(oxazoline) [AraBOX] is described. The novel ligand is prepared in two efficient steps from a bis-[(O-silyl)β-amino alcohol], via conversion into an intermediate bis(benzamide) followed by a one-pot deprotection-activation-ring closure (DARC) oxazoline formation. To our knowledge, this is the first reported synthesis of an oxazoline ring via this DARC method. The synthesis of two precursor bis-β-amino alcohols, (2R,4R)- and meso-2,4-diaminopentane-1,5-diol, derived from D-(+)-arabitol and xylitol, respectively, is also described.

A Gold‐Catalyzed Entry into the Sesquisabinene and Sesquithujene Families of Terpenoids and Formal Total Syntheses of Cedrene and Cedrol

A concise entry into the bicyclic cyclopropyl ketone derivatives 5 and 6 by way of a gold-catalyzed Ohloff-Rautenstrauch-type enyne cycloisomerization is described. The required substrates were prepared by an asymmetric addition of the branched allylzinc reagent 21 to the alkynyl aldehyde 17 mediated by the deprotonated bisoxazoline (BOX) ligand 22. Compounds 5 and 6 were then converted into a host of different members of the sesquisabina- and sesquithuja families of terpenoids, inter alia with the aid of iron-catalyzed cross-coupling reactions. As the relative and absolute configuration of 5 and 6 could be unambiguously established, the synthetic samples allowed the previously unknown stereostructures of various such terpenoids to be unraveled, including cis-sesquisabinene hydrate (33), 7-epi-sesquithujene (36), sesquisabinene B (37) and epoxy-sesquithujene (45). Moreover, the preparation of 6 also constitutes a formal total synthesis of cedrene (11) and cedrol (12).

A General and Efficient Route to 3-O-Modified Carbohydrate Bis(oxazoline) Ligands

An efficient route to derivatives of carbohydrate-based bis(oxazoline) ligands with 3-O substituents of varying steric demand is described. The synthesis of the new ligands proceeds via a thioglucoside key intermediate, the double cyclisation reaction to the desired bis(oxazolines) is initiated with N-iodo succinimide under mild conditions. Employing this strategy, four new 3-O-modified bis(oxazoline) ligands were obtained in good yields.

Theoretical investigation of direct amination of β-ketoesters catalyzed by copper(II)-bisoxazoline(BOX)

The mechanism of the direct amination of beta-keto esters catalyzed by copper(II)-bisoxazoline has been studied by means of density functional theory of B3LYP method. The computational results support the present mechanism, which involves (i) the generation of the enol from beta-keto esters, which coordinates to copper(II)-bisoxazoline. The coordination step appears to be fast, exothermic, and irreversible. (ii) The formation of the sigma(N-C) bond via a six-membered ring transition state after azo dicarboxylate coordination with the chiral catalyst. This step is chirality-control step. (iii) Intramolecular hydrogen migration generates a catalyst-product complex, which can finally yield product. The hydrogen shift is the rate-determining step, which affords the experimentally observed (R)-product. The stereochemical predictions have been rationalized in terms of steric repulsions, showing good agreement with experimental data.

Stereochemical Consequences of Threefold Symmetry in Asymmetric Catalysis: Distorting C3 Chiral 1,1,1‐Tris(oxazolinyl)ethanes (“Trisox”) in CuII Lewis Acid Catalysts

The underlying conceptual differences in exploiting two- and threefold rotational symmetry in the design of chiral ligands for asymmetric catalysis have been addressed in a comparative study of the catalytic performance of bisoxazoline (BOX) and tris(oxazolinyl)ethanes (trisox) containing copper(II) Lewis acid catalysts. The differences become apparent in constructing new catalysts by systematically "deforming" the stereodirecting ligand by inverting chiral centres or replacing chiral by achiral oxazolines. The catalytic alpha-amination of ethyl 2-methylacetoacetate with dibenzyl azodicaboxylate, which occurs with high enantioselectivity for both Ph(2)-BOX and Ph(3)-trisox copper catalysts, has been employed as the test reaction. In the trisox-copper complex [Cu(II)(iPr(3)-trisox)(kappa(2)-O,O'-MeCOCHCOOEt)](+)[BF(4)](-) (1), which was characterised by X-ray diffraction, two of the oxazoline groups are coordinated to the central copper atom, whilst the third oxazoline unit is dangling with the N-donor pointing away from the metal centre. A similar arrangement is found for the stereochemically "mixed" C(1)-trisox complex [Cu(II){(Ph(3)-trisox(R,S,S)}(kappa(2)-O,O'-MeCOCHCOOEt)(H(2)O)](+)[ClO(4)](-) (2), in which the phenyl substituents adopt a first coordination sphere meso arrangement. The almost identical selectivity of the Ph(3)-trisox(R,R,R)- and Ph(2)-BOX(R,R)-derived catalysts is as expected from the proposed model of the active catalyst based on a partially decoordinated podand. The behaviour of the "desymmetrised" trisox-Cu catalysts may be rationalised in terms of a general steady-state kinetic model for the three possible active bisoxazoline-copper species, which are expected to be in rapid exchange with each other in solution. This applies to both the trisox derivatives with stereochemically inverted and achiral oxazoline rings. The study underscores previous observations of superior performance of the catalysts bearing C(3)-chiral stereodirecting ligands as compared to systems of lower symmetry.

Enantioselective Mannich‐Type Reaction of Sulfonylimines Having 2‐Pyridylsulfonyl Group as a Novel Stereocontroller.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Selective Molecular Transformation of 1,2‐Diols Based on Molecular Recognition

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Imidazolium-Based Frameworks: Imidazolium Salt-Oxazoline/Palladium(II) Acetate In Situ Catalyst Systems

New simple imidazolium-based bidentate ligand precursors were prepared by a three-step protocol and bis(oxazoline) ligands were prepared in two steps. A Suzuki-Miyaura reaction was utilized to ascertain the activity of a palladium(II) catalyst system generated in situ from an oxazolinyl-imidazolium cation, a bis(oxazoline), and palladium(II) acetate. Among them, two sterically hindered N-arylimidazolium cations demonstrated their efficiency with both aryl bromides and chlorides in low catalyst-system loading.