Pybox Ligand Research Articles

Ruthenium‐Catalyzed Asymmetric Epoxidation of Olefins Using H2O2, Part I: Synthesis of New Chiral N,N,N‐Tridentate Pybox and Pyboxazine Ligands and Their Ruthenium Complexes

The synthesis of chiral tridentate N,N,N-pyridine-2,6-bisoxazolines 3 (pybox ligands) and N,N,N-pyridine-2,6-bisoxazines 4 (pyboxazine ligands) is described in detail. These novel ligands constitute a useful toolbox for the application in asymmetric catalysis. Compounds 3 and 4 are conveniently prepared by cyclization of enantiomerically pure alpha- or beta-amino alcohols with dimethyl pyridine-2,6-dicarboximidate. The corresponding ruthenium complexes are efficient asymmetric epoxidation catalysts and have been prepared in good yield and fully characterized by spectroscopic means. Four of these ruthenium complexes have been characterized by X-ray crystallography. For the first time the molecular structure of a pyboxazine complex [2,6-bis-[(4S)-4-phenyl-5,6-dihydro-4H-[1,3]oxazinyl]pyridine](pyridine-2,6-dicarboxylate)ruthenium (S)-2 aa, is presented.

Studies on enantioselective allylic oxidation of olefins using peresters catalyzed by Cu(i)-complexes of chiral pybox ligands

Enantioselective allylic oxidation of olefins with various peresters, using a catalytic amount of Cu(I)-pybox complex, can be tuned to achieve high asymmetric induction (up to 98% ee) by choosing a unique combination of a ligand and a perester at room temperature. The asymmetric induction in the reaction strongly depends on the nature of the substituents attached to the aryl ring of peresters. The presence of a gem-diphenyl group at C-5 and secondary or tertiary alkyl substituents at the chiral center (C-4) of the oxazoline rings is crucial for high enantioselectivity. A pi-pi stacking model has been proposed and discussed to explain the stereochemical outcome of the reaction.

Immobilization of Pybox Ligand on Modified Starch

Abstract Starch, one of the most abundant natural polymer was used as support for chiral pyridine–bis(oxazoline) ligand. The corresponding ruthenium complex was used as catalyst in cyclopropanation reaction of styrene with ethyl diazoacetate. Yield, diastereoisomeric excess and enantiomeric excess kept constant after 3 runs.

Observed Instability of Bound Pybox Ligands towards Acetate Counterions

Reaction of Pd(OAc)2 with bis(oxazolinyl)pyridine (pybox) ligands led cleanly to products that contained a ring-opened oxazoline ring. The transformations were formally the result of the attack of bound pybox ligands by acetate counterions, leading to acetate incorporation into the ring-opened products.

The First Solid-Phase Synthesis of Bis(oxazolinyl)pyridine Ligands

The solid-phase synthesis of bis(oxazolinyl)pyridine ligand (Pybox) on Wang resin was described. The pybox ligands (1a-g) were prepared in 66-90% yield. Tertiary Bu-Pybox 1f showed high enantioselectivity for copper-catalyzed asymmetric alkylation of benzylideneaniline with phenylacetylene (83% ee, 63% yield).

Immobilization of Bis(oxazolinyl)pyridines

Bis(oxazolinyl)pyridine ligands (pybox) having various tether groups were anchored on polystyrene resin via copolymerization or grafting. The utility of the polymeric pybox ligands were examined for Ru-catalyzed asymmetric cyclopropanation of styrene. Ligand 2 showed good stability in four subsequent reuses under optimized conditions (52-70% yields, 90:10 trans/cis selectivity and 85-91% ee for trans-cyclopropanes).

Regio‐ and Stereocontrolled Palladium‐ or Iridium‐Catalyzed Allylation

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective Allylation of Aldehydes Catalyzed by Chiral Indium(III) Complexes Immobilized in Ionic Liquids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Hydroxylamines as Oxygen Atom Nucleophiles in Transition‐Metal‐Catalyzed Allylic Substitution.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Direct Catalytic Enantioselective Synthesis of Protected Aryl β‐Hydroxy‐α‐Amino Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Lanthanide Pybox Complexes as Catalysts for Enantioselective Silylcyanation of Aldehydes

Complexes of lanthanide chlorides with pybox ligands catalyze the enantioselective silylcyanation of aromatic and aliphatic aldehydes with ee's of up to 91% under mild and convenient conditions. Studies of catalysts prepared with pybox ligands of varying enantiomeric purity show no marked nonlinear effects, indicating a monometallic transition state. A mechanism for the catalytic reaction is proposed. Crystal structures of [LnCl2(S-Pri-pybox)2][LnCl4(S-Pri-pybox)] (Ln = Eu, Yb) are reported. The structure of the related triflate complex [La(OTf)3(S-Pri-pybox)2] is also reported. Diastereoselectivity has been observed in the reactions of Ln(OTf)3 with racemic Pri-pybox: for Ln = Eu, a heterochiral product containing one R- and one S-pybox ligand is observed, whereas for Ln = Yb a racemic mixture of homochiral bis(pybox) complexes is formed.

Kinetic resolution by copper-catalyzed azide–alkyne cycloaddition

The use of chiral pybox ligands imparts enantioselectivity to the Cu I-catalyzed azide–alkyne cycloaddition reaction, in the form of kinetic resolution of α-chiral azides and desymmetrization of gem-diazides. While levels of selectivity are modest, the results show unequivocally that the process benefits from ligand-accelerated catalysis.

Applications of Enantiopure 4,5-Diphenyl Substituted Box and Pybox Ligands in Asymmetric Catalysis.

For Abstract see ChemInform Abstract in Full Text.

Utility of the Iridium Complex of the Pybox Ligand in Regio‐ and Enantioselective Allylic Substitution.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Direct Catalytic Enantioselective Synthesis of Protected Aryl β‐Hydroxy‐α‐Amino Acids

The combination of three reagents—a tridentate pybox ligand (pybox=pyridine bis(oxazoline)), magnesium perchlorate, and Hünig base (iPr2EtN)—allows the catalytic generation of a chiral glycine enolate from 1 that undergoes highly enantioselective addition to a range of aryl aldehydes 2. The protected aryl β-hydroxy-α-amino acid products obtained include a protected version of one of the aryl serine units present in the glycopeptide antibiotic vancomycin.

Hydroxylamines as Oxygen Atom Nucleophiles in Transition-Metal-Catalyzed Allylic Substitution

[reaction: see text] The viability of hydroxylamines as nucleophiles in transition-metal-catalyzed allylic substitutions was examined. We have found that the oxygen atom of hydroxylamines having an N-electron-withdrawing substituent (also known as hydroxamic acids) acts as a reactive nucleophile. The palladium-catalyzed O-allylic substitution of hydroxylamines with allylic carbonate afforded the linear hydroxylamines. The selective formation of the branched hydroxylamines was observed in iridium-catalyzed reaction. Regio- and enantioselective allylic substitution of the unsymmetrical phosphates with hydroxylamines was studied by using the iridium complex of chiral pybox ligand. The aqueous-medium reaction with hydroxylamines proceeded smoothly in the presence of Ba(OH)(2).H(2)O to give the branched products with good enantioselectivities.

Enantioselective allylation of aldehydes catalyzed by chiral indium(iii) complexes immobilized in ionic liquids

In the presence of chiral catalytic complexes prepared from In(OTf)3 and chiral PYBOX ligands, allytributylstannane reacted with aldehydes in ionic liquids to afford the corresponding homoallylic alcohols in high enantioselectivities (86-94% ee) and good yields (68-89%); the chiral catalysts immobilized in ionic liquids could be reused with comparable enantioselectivities and yields.

Regio- and Stereocontrolled Palladium- or Iridium-Catalyzed Allylation

We studied palladium- or iridium-catalyzed allylation as an effective method for the asymmetric synthesis of α-amino acids, hydroxylamines, oximes, and amines. The stereochemistry of the palladium-catalyzed allylic alkylation of a prochiral diphenylimino glycinate was controlled by chiral PTC, and gave chiral amino acids. In contrast, iridium-catalyzed allylic substitution of diphenylimino glycinate proceeded with good enantio- and diastereoselectivities with a new bidentate chiral ligand to give a novel method for preparing two branched diastereoisomers by simply switching the base. For the synthesis of α,α-disubstituted amino acids, the palladium-catalyzed tandem reaction of dehydroamino acids was developed based on radical chemistry. Next, the viability of oximes and hydroxylamines as oxygen atom nucleophiles in transition metal-catalyzed allylic substitutions was examined. Regioand enantioselective allylic substitution of oximes and hydroxylamines was achieved by using the iridium complex of chiral pybox ligand. Sequential allylic amination gave a novel method for preparing azacycles. Finally, umpolung allylation with aldehyde or imine was studied by using palladium catalyst and indium iodide. The palladium-indium iodide-mediated reaction of chiral 2-vinylaziridines with aldehydride proceeded with excellent diastereoselectivity. The role of water in directing the diastereo- or regioselectivities was investigated in the allylation and propargylation of chiral oxime ether. The allylation of oxime ether with monosubstituted allylic reagents afforded either γ-adduct or α-adduct depending on the reaction conditions.

An Efficient and General One-Pot Method for the Synthesis of Chiral Bis(oxazoline) and Pyridine Bis(oxazoline) Ligands

Abstract: An expeditious method for the synthesis of chiral boxand pybox ligands is reported. The approach is based on a one-potcondensation reaction of chiral b-amino alcohols with a dinitrileusing stoichiometric or catalytic amounts of zinc triflate. Yieldsgreater than 90% are obtained in many cases without the need forfurther purification of the product. Key words: bis(oxazolines), pybox, synthesis, zinc triflate, tolu-ene, chiral ligands Chiral bis(oxazolines) (box) are widely used in the asym-metric catalysis of an increasing variety of organic reac-tions including cyclopropanations, Diels–Alder, ene,aziridination, allylic substitutions, Mukaiyama–Michael,Mukaiyama aldol reactions, 1,2 to mention just a few. Boxsystems bearing a one-carbon spacer between the twooxazoline rings are the most frequently used.Since 1997 many attempts have also been made to supportbox ligands in heterogeneous systems. 3 The introduction of a third coordinating atom into the linkbetween the two oxazoline rings has led to the develop-ment of tridentate bis(oxazoline) ligands, among whichpyridine bis(oxazoline) (pybox) derivatives represent thebest known examples. These ligands have been success-fully used in the same types of reactions as bis(oxazol-ines),

Asymmetric versus C2‐Symmetric Ligands: Origin of the Enantioselectivity in Ruthenium–Pybox‐Catalyzed Cyclopropanation Reactions

One stereogenic center suffices in pyridinebis(oxazoline) (pybox) ligands for efficient ruthenium-catalyzed cyclopropanation. A molecular-modeling study reveals the main origin of the enantioselectivity to be unfavorable steric interactions between the substituent on pybox and styrene in a Si approach to the carbene intermediate (see picture). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z461418_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.