Chiral Phosphapalladacycle Research Articles

Efficient Synthesis of Malonate Functionalized Chiral Phosphapalladacycles and their Catalytic Evaluation in Asymmetric Hydrophosphination of Chalcone

Four chiral phosphapalladacycle complexes functionalized with the malonate moiety at the chiral carbon have been synthesized via a consecutive asymmetric hydrophosphination and cyclometallation protocol. High conversions were achieved in the P–H addition reaction, which was itself catalyzed by a phosphapalladacycle. Moderate to good enantioselectivities, were obtained for this step depending on the nature of the functional groups present on the naphthalene backbone. In contrast, the outcome of the subsequent cyclometallation reaction relies highly on the character of the functional groups. The catalytic potential of the synthesized phosphapalladacycle complexes was evaluated in the hydrophosphination reaction of chalcone with moderate results.

Desymmetrization of Achiral Heterobicyclic Alkenes through Catalytic Asymmetric Hydrophosphination.

Asymmetric addition of diarylphosphines to oxa- and azabicyclic alkenes proceeded in the presence of a chiral phosphapalladacycle catalyst and a mild acid at room temperature to give exclusively the enantioenriched addition products in excellent yields and good selectivities. Three new chiral carbon centers were generated stereoselectively by the catalytic hydrophosphination reaction.

Efficient access to a designed phosphapalladacycle catalyst via enantioselective catalytic asymmetric hydrophosphination.

A chiral phosphine auxiliary was generated with excellent ee via catalytic asymmetric hydrophosphination of 3-(naphthalen-1-ylmethylene)pentane-2,4-dione. The subsequent metal complexation of the monophosphine yielded two different coordination complexes depending on the reaction conditions. The ortho-palladation of both coordination complexes resulted in the formation of a single dimeric phosphapalladacycle complex that could be further converted to the monomeric bisacetonitrile derivative. Moreover, the palladium complex exhibits interesting oxophilicity as the stable bisaquo derivative could be isolated and characterized crystallographically. The catalytic potential of the phosphapalladacycle was also demonstrated.

ChemInform Abstract: Asymmetric Synthesis of P‐Stereogenic Diarylphosphinites by Palladium‐Catalyzed Enantioselective Addition of Diarylphosphines to Benzoquinones.

The reaction of phenyl(2,4,6-trimethylphenyl)phosphine with a substituted benzoquinone in the presence of a chiral phosphapalladacycle complex as a catalyst and triethylamine in chloroform at -45 °C proceeded in a new type of addition manner to give a high yield of a 4-hydroxyphenyl phenyl(2,4,6-trimethylphenyl)phosphinite with 98% enantioselectivity, which is a versatile intermediate readily convertible into various phosphines and their derivatives with high enantiomeric purity.

Chiral Palladacycle Catalysts Generated on a Single-Handed Helical Polymer Skeleton for Asymmetric Arylative Ring Opening of 1,4-Epoxy-1,4-dihydronaphthalene

Post-polymerization CH activation of poly(quinoxaline-2,3-diyl)-based helically chiral phosphine ligands (PQXphos) with palladium(II) acetate afforded chiral phosphapalladacycles quantitatively. In situ generated palladacycles exhibited enantioselectivities up to 94 % ee in the palladium-catalyzed asymmetric ring-opening arylation of 1,4-epoxy-1,4-dihydronaphthalenes with arylboronic acids.

Chiral palladacycle catalysts generated on a single-handed helical polymer skeleton for asymmetric arylative ring opening of 1,4-epoxy-1,4-dihydronaphthalene.

Post-polymerization CH activation of poly(quinoxaline-2,3-diyl)-based helically chiral phosphine ligands (PQXphos) with palladium(II) acetate afforded chiral phosphapalladacycles quantitatively. In situ generated palladacycles exhibited enantioselectivities up to 94 % ee in the palladium-catalyzed asymmetric ring-opening arylation of 1,4-epoxy-1,4-dihydronaphthalenes with arylboronic acids.

Asymmetric Synthesis of P-Stereogenic Diarylphosphinites by Palladium-Catalyzed Enantioselective Addition of Diarylphosphines to Benzoquinones

The reaction of phenyl(2,4,6-trimethylphenyl)phosphine with a substituted benzoquinone in the presence of a chiral phosphapalladacycle complex as a catalyst and triethylamine in chloroform at -45 °C proceeded in a new type of addition manner to give a high yield of a 4-hydroxyphenyl phenyl(2,4,6-trimethylphenyl)phosphinite with 98% enantioselectivity, which is a versatile intermediate readily convertible into various phosphines and their derivatives with high enantiomeric purity.

Palladium‐Mediated [2+1] Cycloaddition of Norbornene Derivatives with Ynamides

AbstractAn efficient palladium‐catalyzed [2+1] cycloaddition between ynamides and norbornenes or norbornadienes is reported. Both phosphapalladacycles and palladium/secondary phosphine oxide catalytic systems were found to be competent for the transformation allowing the preparation of aminomethylenecyclopropanes. The reaction showed general applicability to various functionalized bicyclo[2.2.1]hept‐2‐enes and ynamides. A chiral phosphapalladacycle was tested to carry out this transformation in an enantioselective fashion.

Chiral Phosphapalladacycles as Efficient Catalysts for the Asymmetric Hydrophosphination of Substituted Methylidenemalonate Esters: Direct Access to Functionalized Tertiary Chiral Phosphines

A chiral palladacycle-promoted enantioselective asymmetric hydrophosphination of substituted methylidenemalonate esters using diphenylphosphine that provides direct access to chiral tertiary phosphines is reported. Screening of three easily accessible C,N and C,P palladacycles as catalysts for this synthetic scenario provided insights into critical factors in catalyst design that influence the activation and stereochemistry in Pd(II)-catalyzed asymmetric P–H addition reactions involving such activated substrates.

Asymmetric synthesis and absolute configuration of a planar chiral phosphapalladacycle with a ferrocenyl framework

A monodentate optically active tertiary α-ferrocenylethylphosphine was prepared from the corresponding tertiary α-ferrocenylethylamine; Me 2N group substitution by a tert-Bu 2P group occurs with complete retention of the enantiomeric composition and absolute configuration of the α-carbon stereocentre. The cyclopalladation of this phosphine ligand results in the formation of a phosphapalladacycle bearing the elements of central and planar chirality with a high diastereoselectivity. The enantiomeric composition of the CP-palladacycle was determined by 31P{ 1H} NMR spectroscopy using ( S)-prolinate as a chiral derivatizing agent. The structure and absolute configuration of the phosphapalladacycle were established using NMR spectroscopy and an X-ray diffraction study of its ( S)-prolinate derivative.

Synthesis of Planar Chiral Phosphapalladacycles by N-Acyl Amino Acid Mediated Enantioselective Palladation

Reaction of 2-(dicyclohexylphosphino)phenylferrocene with sodium tetrachloropalladate in the presence of 1 equiv of (R)-N-acetylphenylalanine in MeOH/H2O/CH2Cl2 at pH 8 resulted in the formation of bis(μ-chloro)bis[2-(2-(dicyclohexylphosphino)phenyl)ferrocene-C1,P]dipalladium(II) with a 59% enantiomeric excess of the pS planar chiral palladacycle. Similarly, (dimethylaminomethyl)ferrocene gave (pS)-bis(μ-chloro)bis[2-(dimethylaminomethyl)ferrocene-C1,P]dipalladium(II) in 96% ee. An intramolecular isotope effect of 2.3 was observed for the palladation of 2-(diphenylphosphino)phenylferrocene under these conditions.

Synthesis, Coordination Characteristics, Conformational Behavior, and Bond Reactivity Studies of a Novel Chiral Phosphapalladacycle Complex

A novel five-membered dimeric phosphapalladacycle was prepared using palladium(II) acetate as the ortho-palladation source. A successful optical resolution of the palladacycle was achieved through the separation of its (S)-prolinate derivatives by fractional crystallization using different solvent systems. Both the (R,R)- and (S,S)-di-μ-chloro dimeric palladium complexes can be obtained by treating the corresponding prolinato derivatives with 1 M hydrochloric acid, and the absolute configurations of both optically active dimers were concluded from the X-ray diffration studies. Two phosphine ligands, triphenylphosphine (PPh3) and 3,4-dimethyl-1-phenylphosphole (dmpp), were able to coordinate with the dimeric palladium complex, and thus the palladacycle’s coordination characteristics were studied by both 31P NMR and X-ray diffraction. The phosphapalladacycle’s conformational behavior was further studied by the 2D 1H−1H ROESY NMR of its acetylacetonate derivative, which indicated that the α-methyl group was ...

New approach to chiral phosphapalladacycles: first optically active phosphinite PC-palladacycle with non-metallocenic planar chirality

A new proposed methodology for the preparation of phosphapalladacycles in enantiopure form includes the use of the same optically active cyclopalladated CN-reagent for both resolution of a racemic ligand and subsequent direct C–H bond activation of the enantiopure ligand via the cyclopalladated ligand exchange reaction. This protocol was successfully employed for the preparation of the complex, which is both the first PC-palladacycle with a non-metallocenic planar chirality based on the [2.2]paracyclophane framework and the first representative of chiral phosphinite PC-palladacycles.

Enantiomerically pure cyclopalladated diazaphospholidine

Enantiomerically pure ( S)-2-(anilinomethyl)pyrrolidine ( S)- 2 was obtained from ( S)-proline using a modified four-step procedure in a total yield of 56%. Diamine ( S)- 2 was converted to diazaphospholidine ( S)- 1 using o TolP(NMe 2) 2. The enantiomeric purity of ligand ( S)- 1 and diamine ( S)- 2 was determined by 31P and 1H NMR spectroscopy, respectively, using a CN-palladacycle for their chiral derivatization. Direct cyclopalladation of ( S)- 1, using Pd(OAc) 2 in toluene under mild conditions regioselectively afforded the cyclopalladated complex with the (sp 2)C–Pd bond. The aromatic C–H bond activation was confirmed by NMR spectral data and X-ray diffraction study of the PPh 3 derivative of the new P ∗, C ∗, N ∗-chiral phosphapalladacycle.

Stereochemical Investigations of a Novel Class of Chiral Phosphapalladacycle Complexes Derived from 1-[(2,5-Dimethyl)phenyl]ethyldiphenylphosphine

The phosphapalladacycle derived from 1-(2',5'-dimethylphenyl)ethyldiphenylphosphine has been prepared in the optically active and racemic forms. The phosphine was synthesized as a racemate by the treatment of 1-chloro-1-(2',5'-dimethylphenyl)ethane with sodium diphenylphosphide in THF. The racemic phosphapalladacycle was subsequently obtained as the chloro-bridged dimer by the treatment of the phosphine with palladium(II) acetate followed by anion metathesis with lithium chloride. Alternatively, the phosphine could be optically resolved via metal complexation using (R,R)-bis(mu-chloro)bis{1-[1-(N,N-dimethylamino)ethyl]naphthyl-C(2),N}dipalladium(II) as the resolving agent. An efficient separation of the resulting diastereomeric complexes was achieved by silica gel chromatography. The obtained optically resolved diastereomers were next subject to chemoselective removal of the (R)-N,N-(dimethylamino)-1-(1-naphthyl)ethylaminate auxiliary by treatment with concentrated hydrochloric acid. This process yielded the binuclear dimer complexes containing the resolved eta(1)-P ligand. Cyclopalladation of the coordinated phosphine could next be performed by treatment of its eta(1)-P binuclear dimer with silver(I) hexafluorophosphate(V) in a dichloromethane/water mixture followed by treatment with lithium chloride, giving rise to a pair of optically pure enantiomeric dimers with [alpha](D) -322 and +319 degrees in CH(2)Cl(2). Despite the possibilities of the phosphine to attain a five- membered structure by ortho-palladation or a six-membered ring formation by aliphatic C-H bond activation, only the former was observed. X-ray crystallographic data of the meso dimer and an acetylacetonate derivative indicated that the phosphapalladacycle alpha-C methyl substituent was axially located. The 2-D (1)H-(1)H ROESY spectrum of the acetylacetonate derivative further revealed that the phosphapalladacycle was conformationally rigid in CDCl(3).

Synthesis of Planar Chiral Phosphapalladacycles by Highly Enantioselective Transcyclopalladation

The first highly enantioselective synthesis of planar chiral ferrocene phosphapalladacycles was performed by high-yielding asymmetric transcyclopalladation with cobalt oxazoline palladacycles (COP). Use of di-mu-acetatobis[(eta5-(S)-(pR)-2-(2'-(4'-isopropyl)oxazolinyl)cyclopentadienyl-C1,N3')(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium(II), followed by acetate/chloride ligand exchange, gave (pS)-di-mu-chloro[2-(2-dicyclohexylphosphino)phenylferroene-C1,P)dipalladium(II) (95% ee). Similarly, diastereomeric di-mu-acetatobis[(eta5-(S)-(pS)-2-(2'-(4'-tert-butyl)oxazolinyl)cyclopentadienyl-C1,N3')(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium(II) led to the enantiomeric (pR)-phosphapalladacycle (95% ee), revealing the control of these reactions by the element of planar chirality in COP. The reactions were extended to the synthesis of (pS)- and (pR)-di-mu-chloro[2-(2-diphenylphosphino)phenylferroene-C1,P)dipalladium(II) (78 and 92% ee, respectively). In all cases, the palladium-free precursors to COP were recovered for recycling.

ChemInform Abstract: New Highly Active Chiral Phosphapalladacycle Catalysts. First Isolation and Characterization of a Pd(IV) Intermediate.

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P*-Chiral phosphapalladacycle as derivatizing agent for enantiomeric purity determination of α-amino acids by means of 31P NMR spectroscopy

A P*-chiral cyclopalladated complex was shown to be an efficient chiral derivatizing agent for enantiomeric excess determination of α-amino acids by 31P NMR technique. The main advantages of this type of reagent are discussed.

Highly diastereoselective cyclopalladation of α-ferrocenylethylphosphine: X-ray study of the first phosphapalladacycle of planar chirality

First planar chiral phosphapalladacycle was prepared in diastereomerically pure state via direct cyclopalladation of the di- tert-butyl-1-ferrocenylethylphosphine. The palladacycle structure was confirmed by 1 H NMR spectra; relative configuration of central and planar chirality was determined by an X-ray diffraction study of the triphenylphosphine adduct.

New highly active chiral phosphapalladacycle catalysts. First isolation and characterization of a Pd(iv) intermediate

The synthesis and characterization of a new active P*-active phosphapalladacycle and its successful use in the asymmetric hydroarylation of norbornene with turnover numbers (TONs) of up to 1010 is described.