Pybox Research Articles

ChemInform Abstract: Chiral Dinuclear Phthalazine‐Bridged Bisoxazoline Ligands: Synthesis and Application in Enantioselective Cu‐Catalyzed Conjugate Addition of ZnEt2 to Enones.

AbstractA novel class of ligands, represented by PBO, is developed and successfully applied to the title reaction.

ChemInform Abstract: Asymmetric 1,3‐Dipolar Cycloaddition Reactions Catalyzed by Heterocycle‐Based Metal Complexes

AbstractReview: 116 refs.

Novel chiral bisoxazoline ligands with a bipyridinyl backbone: preparation and interesting complexation behavior

Novel C2-symmetric chiral bisoxazoline ligands with a bipyridinyl backbone were prepared with ease from 3,3′-dicarbomethoxy-2,2′-bipyridine and enantiomerically pure 2-amino alcohols via a corresponding amide as intermediate. Interestingly, when these ligands were coordinated with Pd(II) and Cu(I), different complexation behaviors were found.

Chiral dinuclear phthalazine bridged bisoxazoline ligands: synthesis and application in enantioselective Cu-catalyzed conjugate addition of ZnEt2 to enones

A new class of chiral dinuclear ligands with phthalazine bridged bisoxazoline scaffold was designed and prepared in convenient synthetic routes. 1H NMR analysis showed that this class of ligands could coordinate with two metal ions, either same or different. These ligands afforded good to excellent yields and enantioselectivities in Cu-catalyzed conjugate addition of ZnEt2 to enones.

Influence of multidentate N-donor ligands on highly electrophilic zinc initiator for the ring-opening polymerization of epoxides

A set of multidentate ligands have been synthesized and used to stabilize the putative highly electrophilic zinc species initiating ring-opening polymerization (ROP) of cyclohexene oxide (CHO) and propylene oxide (PO). Reaction of the bidentate C 2-chiral bis(oxazoline) ligand ( R2,R3BOX: R 2 = (4 S)- tBu, R 3 = H ( a); R 2 = (4 S)-Ph, R 3 = H ( b); R 2 = (4 R)-Ph, R 3 = (5 S)-Ph ( c)) with Zn(R 1) 2 (R 1 = Et ( 1), Me ( 2)) led to the heteroleptic three-coordinate complexes ( R2,R3BOX)ZnR 1, 1a– c and 2a, which were isolated in 92–96% yield. Next, two pyridinyl-functionalized N-heterocyclic carbene (NHC) ligands have been designed and synthesized: the 1,3-bis(2-pyridylmethyl)imidazolinium salt ( d) and the protected NHC adduct 2-(2,3,4,5,6-pentafluorophenyl)-1,3-bis(2-pyridylmethyl)imidazolidine ( e). The reaction of ligands d and e with ZnEt 2 led directly to the formation of (NHC)ZnEt(Cl) 3d complex with ethane elimination and the adduct (NHC–C 6F 5(H))ZnEt 2 4e, respectively, in high yield. In situ combinations of selected complexes 1a– c, 3d and 4e with B(C 6F 5) 3 (1 or 2 equivalents) give active systems for ROP, with high productivity (3.3–5.9 10 6 g polym. mol Zn −1 h −1) and high molecular weight ( M n up to 132 10 3 g mol −1) for CHO polymerization. Although the in situ B(C 6F 5) 3-activated zinc species were not isolated, the sterically demanding BOX ligands ( 1c > 1b > 1a) and functionalized NHC ligands seem to enhance the stability of highly electrophilic zinc complexes over ligand redistribution, allowing a better control of the cationic ROP as reflected particularly for 3d and 4e complexes by their respective efficiency (42–88%).

Spiro-2,2′-bichroman-based bisoxazoline (SPANbox) ligands for ZnII-catalyzed enantioselective hydroxylation of β-keto esters and 1,3-diester

A new type of spiro bisoxazoline ligand (SPANbox) has been developed on the basis of the spiro-2,2′-bichroman motif and bisoxazoline chelating units. The Zn(II) complexes of SPANbox showed excellent activity (98–99% yield) and enantioselectivity (90–98% ee) in the catalysis of hydroxylation of various β-keto esters and 1,3-diester with catalyst loading of 0.1–5 mol%. The performance of SPANbox in the present catalytic system was found to be significantly superior to the commonly used classic bisoxazoline ligands, such as (R,R)-Ph-Box or (S,S)-tBu-PyBox, indicating the advantage of the present spiro ligand skeleton.

On the enantioselectivity of aziridination of styrene catalysed by copper triflate and copper-exchanged zeolite Y: consequences of the phase behaviour of enantiomeric mixtures of N-arene-sulfonyl-2-phenylaziridines

By synthesising S-2-phenyl-N-(4-nitrophenyl)aziridine from S-phenylglycinol, it has been demonstrated that the aziridination of styrene by [N-(4-nitrobenzenesulfonyl)imino]phenyliodinane (nosyliminophenyliodinane, PhINNs) in the presence of S,S-2,2'-isopropylidene-bis(4-phenyl-2-oxazoline), catalysed by copper(II) triflate in CH(3)CN solution or heterogeneously by CuHY, has predominantly an R-configuration. The enantioselectivity of the aziridination of styrene by [N-arenesulfonylimino]-phenyliodinanes catalysed by copper-exchanged zeolite Y (CuHY), in conjunction with a chiral bis-oxazoline ligand, has been re-examined. In the case of PhINNs, it is shown that the product mixture of enantiomeric aziridines, on treatment with hexane, gives rise to a solid phase of low enantiomeric excess (ee) and a solution phase of high ee. Separation of the solid phase and recrystallisation afforded a true racemate (racemic compound), which has been confirmed by X-ray crystallography. The aziridine obtained from the solution phase could be recrystallised to produce the pure enantiomer originally in excess. A consequence of the new findings is that previous reports on the enantioselectivity of copper-catalysed aziridination, both in heterogeneous and homogeneous conditions, should be regarded with caution if the analytical procedure involved HPLC with injection of the enantiomeric mixture in a hexane-rich solvent. Such a method has been used in previous work from this laboratory, but has also been used elsewhere, following the procedure developed by Evans and co-workers when the (homogeneous) copper-catalysed aziridination by PhINTs was first discovered. Evidently, the change of substituent in the benzenesulfonyl group reduces the solubility in hexane, affording a solution phase of enhanced ee.

Modular ligand variation in calcium bisimidazoline complexes: effects on ligand redistribution and hydroamination catalysis

A series of calcium complexes supported by chiral bisimidazoline ligands have been studied in the catalytic intramolecular hydroamination/cyclisation of amino-olefins. The complexes [Ca(R-BIM){N(SiMe(3))(2)}(THF)] (R = 4-C(6)H(4)Me, 5a, 4-C(6)H(4)F, 5b and (t)Bu, 5c) have given competitive enantioselectivities (up to 12%) when compared to current literature studies involving calcium. Bisimidazolines offer a significant advance over similar bisoxazoline ligands, by allowing a greater structural variance through a modular synthetic pathway.

ChemInform Abstract: Recent Progress in Homogeneous Supported Asymmetric Catalysis: Example of the BINAP and the BOX Ligands

AbstractReview: 61 refs.

Enantioselective Copper-Catalyzed Intramolecular O−H Insertion: An Efficient Approach to Chiral 2-Carboxy Cyclic Ethers

A copper-catalyzed asymmetric intramolecular O-H insertion of ω-hydroxy-α-diazoesters has been accomplished by using chiral spiro bisoxazoline ligands. This highly enantioselective intramolecular O-H insertion reaction provides an efficient approach to a variety of synthetically important chiral 2-carboxy cyclic ethers with different ring sizes as well as substitution patterns.

Synthesis of novel chiral bisoxazoline ligands with a spiro[4,4]-1,6-nonadiene skeleton

A new type of chiral bisoxazoline ligands 1 based on spiro[4,4]-1,6-nonadiene backbone was easily prepared in six steps from racemic spiro[4,4]-nonane-1,6-dione, with the Pd-catalyzed coupling of the enol triflates with CO and amino alcohols as the key steps for the construction of the oxazoline moiety. The structure of the ligand (R,S,S)-1b was unambiguously established by X-ray crystallographic analysis. The chiral Cu(II) complex generated in situ from the combination of spiro bisoxazoline ligand (S,S,S)-1c and Cu(OTf)2 was effective in the catalysis of asymmetric chlorination of the β-ketoester, methyl 1-oxo-2,3-dihydro-1H- indene-2-carboxylate, affording the corresponding chlorinated derivative in 99% yield with 17% ee.

Novel C2-symmetric bisoxazolines with a chiral trans-(2 R,3 R)-diphenylcyclopropane backbone: preparation and application in several enantioselective catalytic reactions

Various chiral bisoxazoline ligands with a chiral trans-(2 R,3 R)-diphenylcyclopropane backbone have been efficiently synthesized (five examples). These chiral ligands were tested and compared in palladium(0)-catalysed enantioselective allylic alkylations (up to 97% ee), copper(I)-catalysed enantioselective cyclopropanations (up to 89% ee) and aziridinations (up to 90% ee). We observed that the presence of a stereogenic centre on the oxazoline moiety is mandatory in order to obtain acceptable enantioselectivities.

Copper(II)-Catalyzedsyn-Selective Henry Reaction

The authors report a highly diastereo- and enantioselective Henry reaction of nitroethane with aromatic and aliphatic aldehydes. The bisimidazoline ligand outperforms conventional bisoxazoline ligands in both yield and selectivity.

ChemInform Abstract: Asymmetric Copper-Catalyzed Cyclopropanation of Trisubstituted and Unsymmetrical cis-1,2-Disubstituted Olefins: Modified Bisoxazoline Ligands.

ChemInform Abstract: Asymmetric Copper-Catalyzed Cyclopropanation of Trisubstituted and Unsymmetrical cis-1,2-Disubstituted Olefins: Modified Bisoxazoline Ligands.

Configurationally Labile Enantioenriched Lithiated 3-Arylprop-2-enyl Carbamates: Joint Experimental and Quantum Chemical Investigations on the Equilibrium of Epimers

Experimental investigations as well as high-level quantum chemical calculations are performed on the two epimeric pairs of complexes 4.2 and 6.2 obtained by lithiation of cinnamyl carbamate (1) and 1-naphthyl derivative 5 in the presence of BOX ligands (S,S)- and (R,R)-2. Indeed, in the case of configurationally labile complexes and a dynamic thermodynamic resolution, which is found to take place, one of both epimers is energetically favored. The quantum chemical computations allow the prediction of the enantiomeric excess that can be expected.

ChemInform Abstract: Bisoxazoline and Bioxazoline Chiral Ligands Bearing 4-Diphenylmethyl Shielding Substituents. Diels-Alder Reaction of Cyclopentadiene with 3-Acryloyl-2-oxazolidinone Catalyzed by the Aqua Nickel(II) Complex.

Enantiopure 2-amino-3,3-diphenyl-1-propanol has been synthesized by the hidantoin route starting from diphenylacetaldehyde, followed by subsequent functional group transformations and optical resolution by a chiral HPLC. This amino alcohol can be converted into two new chiral ligands: 4,4′-bis(diphenylmethyl)-2,2′-bioxazoline and 2,2′-isopropylidenebis(4-diphenylmethyloxazoline), and further to complexes with copper(II) trifluoromethanesulfonate and nickel(II) perchlorate hexahydrate. The nickel(II) aqua complex derived from the bisoxazoline effectively catalyzes the Diels-Alder reactions of cyclopentadiene with 3-acryloyl-2-oxazolidinone in high endo-selectivities and moderate enantioselectivities through a square planar transition structure.

ChemInform Abstract: Asymmetric Copper-Catalyzed [2,3]-Sigmatropic Rearrangements of Alkyl- and Aryl-Substituted Allyl Sulfides.

The asymmetric copper-catalyzed generation and subsequent [2,3]-sigmatropic rearrangement of sulfur ylides is strongly dependent on the structure of the starting allyl sulfide. A series of alkyl and aryl substituted allyl sulfides (2a−i) were reacted with ethyl diazoacetate in the presence of copper triflate (CuOTf) and a C2-symmetric bis-oxazoline ligand (5a−c). The degree of asymmetric induction ranged from 2.8% for allyl methyl sulfide (2a) to 60% for (1S,2S,5R)-(+)-allyl menthyl sulfide (2d). The enantioselectivity of the reactions was also dependent on the electronic nature of the sulfide; allyl phenyl sulfide (2e) gave a 14% ee, whereas allyl p-methoxyphenyl sulfide (2i) produced only an 8% ee. The stereochemistry of 2d and (1R,2S,5R)-(+)-allyl menthyl sulfide (7) was assigned on the basis of NMR spectroscopic experiments.

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.

4,4′BOX based catalysts: Synthesis, structure and catalytic application

Abstract The synthesis of two new 4,4′ bisoxazoline ligands is described. The use of copper complexes of these and three other recently described related ligands as catalysts in a cyclopropanation reaction is discussed. The first structural data on one such chiral copper complex is reported herein.

Copper Bisoxazoline Catalyzed Enantioselective S-H Insertion

The authors report an enantioselective synthesis of α-mercaptoesters by insertion of S-H bonds into copper carbenoids generated from α-diazoesters. The use of their spiro bisoxazoline (spirobox) ligands is the key to attaining high yields and selectivity. The free thiol could be obtained by using trityl thiol for S-H insertion followed by mild deprotection without loss of enan­tiomeric excess (one example). This work is an ­extension of previous methodologies on insertion into N-H and O-H bonds using a similar catalytic system (J. Am. Chem. Soc. 2007, 129, 5834; J. Am. Chem. Soc. 2007, 129, 12616).