Enantioselective separation on a naturally chiral surface

Kinked-stepped, high Miller index surfaces of metal crystals are chiral and, therefore, exhibit enantiospecific properties. Previous temperature-programmed desorption (TPD) spectra have shown that the desorption energies of R-3-methylcyclohexanone (R-3-MCHO) on the chiral Cu(643)(R) and Cu(643)(S) surfaces are enantiospecific (J. Am. Chem. Soc. 2002, 124, 2384). Here, a comparison of the TPD spectra from Cu(111), Cu(221), Cu(533), Cu(653)(R&S), and Cu(643)(R&S) surfaces reveals that the enantiospecific desorption occurs from the chiral kink sites on the Cu(643) surfaces. Titration of the chiral kink sites with I atoms confirms this assignment of desorption features in the TPD spectra. Finally, the enantiospecific difference in the desorption energies of R- and S-3-MCHO has been used as the basis for demonstration of an enantioselective, kinetic separation of racemic 3-MCHO into its purified components during adsorption and desorption on the Cu(643)(R&S) surfaces.     

Enantiospecific desorption of chiral compounds from chiral Cu(643) and achiral Cu(111) surfaces

Temperature-programmed desorption (TPD) experiments have been conducted to investigate enantiospecific desorption from chiral single-crystal surfaces. The (643) and (six four three) planes of face-centered cubic metals such as Cu have kinked and stepped structures which are nonsuperimposable mirror images of one another and therefore are chiral. These chiral surfaces are denoted Cu(643)(R) and Cu(643)(S). We have observed that the desorption energies of (R)-3-methylcyclohexanone and (R)- and (S)-propylene oxides from the Cu(643)(R) and Cu(643)(S) surfaces depend on the relative handedness of the adsorbate/substrate combination. Since the (643) surface is comprised of terraces with local (111) orientation which are separated by kinked monatomic steps, it is instructive to perform TPD experiments with these chiral compounds on the achiral Cu(111) surface. These experiments have given some insight into the adsorption sites for the chiral molecules on the Cu(643) surfaces. There are several high-temperature features in the TPD spectra of the chiral compounds that only appear in the spectra from the (643) surfaces and thus are attributed to molecules adsorbed at or near the kinked steps. In addition there are lower temperature desorption features observed on the Cu(643) surfaces which occur in the same temperature range as desorption features observed on the Cu(111) surface. These features observed on the (643) surfaces are attributed to desorption from the flat (111) terraces.     

Probing enantioselectivity on chirally modified Cu(110), Cu(100), and Cu(111) surfaces

Temperature programmed desorption methods have been used to probe the enantioselectivity of achiral Cu(100), Cu(110), and Cu(111) single crystal surfaces modified by chiral organic molecules including amino acids, alcohols, alkoxides, and amino-alcohols. The following combinations of chiral probes and chiral modifiers on Cu surfaces were included in this study: propylene oxide (PO) on L-alanine modified Cu(110), PO on L-alaninol modified Cu(111), PO on 2-butanol modified Cu(111), PO on 2-butoxide modified Cu(100), PO on 2-butoxide modified Cu(111), R-3-methylcyclohexanone (R-3-MCHO) on 2-butoxide modified Cu(100), and R-3-MCHO on 2-butoxide modified Cu(111). In contrast with the fact that these and other chiral probe/modifier systems have exhibited enantioselectivity on Pd(111) and Pt(111) surfaces, none of these probe/modifier/Cu systems exhibit enantioselectivity at either low or high modifier coverages. The nature of the underlying substrate plays a significant role in the mechanism of hydrogen-bonding interactions and could be critical to observing enantioselectivity. While hydrogen-bonding interactions between modifier and probe molecule are believed to induce enantioselectivity on Pd surfaces (Gao, F.; Wang, Y.; Burkholder, L.; Tysoe, W. T. J. Am. Chem. Soc. 2007, 129, 15240-15249), such critical interactions may be missing on Cu surfaces where hydrogen-bonding interactions are believed to occur between adjacent modifier molecules, enabling them to form clusters or islands.     

Characterization of enantiospecific chemisorption on chiral Cu surfaces vicinal to Cu(111) and Cu(100) using density functional theory

Surfaces of simple fcc metals such as Cu with nonzero and unequal Miller indices are intrinsically chiral. Density functional theory (DFT) calculations are a useful way to study the enantiospecific adsorption of small chiral molecules on these chiral metal surfaces. We report DFT calculations of seven chiral molecules on several structurally distinct chiral Cu surfaces. These surfaces include two surfaces with (111)-oriented terraces and one with (100)-oriented terraces. Calculations are also described on a surface that was modified to mimic the surface structures that typically appear on real metal surfaces following thermally driven fluctuations in step edges. Our results provide initial information on how variation in the surface structure of intrinsically chiral metal surfaces can affect the enantiospecific adsorption of small molecules on these surfaces.     

The Electron Spin as a Chiral Reagent

We show that enantioselective reactions can be induced by the electron spin itself and that it is possible to replace a conventional enantiopure chemical reagent by spin‐polarized electrons that provide the chiral bias for enantioselective reactions. Three examples of enantioselective chemistry resulting from electron‐spin polarization are presented. One demonstrates the enantioselective association of a chiral molecule with an achiral self‐assembled monolayer film that is spin‐polarized, while the other two show that the chiral bias provided by the electron helicity can drive both reduction and oxidation in enantiospecific electrochemical reactions. In each case, the enantioselectivity does not result from enantiospecific interactions of the molecule with the ferromagnetic electrode but from the polarized spin that crosses the interface between the substrate and the molecule. Furthermore, the direction of the electron‐spin polarization defines the handedness of the enantioselectivity. This work demonstrates a new mechanism for realizing enantioselective chemistry.     

Charge-transfer spectra of structurally characterized mixed-valence thiolate-bridged Cu(I)/Cu(II) cluster complexes

A series of Cu(II) and Cu(I)/Cu(II) complexes containing the cis-N(amine)(2)S(thiolate)(2) copper complex rac-2 has been synthesized to provide a basis for understanding the charge-transfer spectra of mixed-valence thiolate-bridged Cu(I)/Cu(II) complexes. In combination with Cu(Me(2)-13-N(4)ane), rac-2 yields a monobridged dinuclear homovalent adduct, rac-5, while reaction with CuCl yields the mixed-valance pentanuclear complex rac-6. In the presence of Cu(II)(acac)(2), chiral R,R-1 reacts to form a mixed-valence pentanuclear cation R,R-7. rac-6 exhibits a relatively short Cu(I). Cu(II) contact [2.8231(9) A] and associated structural features that suggest the presence of a weak Cu(I).Cu(II) interaction in a valence-trapped system. Additional structural features in rac-6 and R,R-7 include singly and doubly bridging thiolates, three- and four-coordinated Cu(I) ions, and varying Cu(I) ligand sets. These features extend the types and complexities of electronic absorptions significantly. Spectra of rac-6 and R,R-7 exhibit multiple overlapping absorptions over the entire visible and ultraviolet spectral regions studied, consonant with these observations. Trends resulting from variations in structure type and oxidation state permit a first approach toward developing a detailed assignment of the individual ligand Rydberg, LF, LMCT, MLCT, and possible MMCT absorptions in these complexes.     

Recoverable (R)- and (S)-binap-Ag(I) complexes for the enantioselective 1,3-dipolar cycloaddition reaction of azomethine ylides

The first enantioselective 1,3-dipolar cycloaddition reaction of amino acid derived azomethine ylides and maleimides catalyzed by very stable and recyclable chiral (R)- or (S)-binap-AgClO(4) complexes is described. The reactions are performed at room temperature, in good yields, with high endo diastereoselectivity and enantioselectivity, the complex being recovered by simple filtration.     

The influence of anions and kink structure on the enantioselective electro-oxidation of glucose

The electro-oxidation of glucose in sulfuric acid using well-defined chiral platinum single crystal electrodes has been demonstrated previously to be an enantioselective reaction with the degree of enantioselectivity being dependent on the surface density of kink sites. The chirality of the surface originates from the microstructure of the kink site whereby the sequence of the three fundamental adsorption sites [111], [100] and [110] constituting the kink may be viewed from the electrolyte phase either in a clockwise (R-enantiomer) or anti-clockwise (S-enantiomer) fashion. In the present study, this work is extended to examine the role of both kink structure and specifically adsorbed anions on the mechanism of chiral discrimination. Kinked surfaces based on [111] terraces (Pt[976],Pt[643] and Pt[531]),[100] terraces (Pt[721]) and [110] terraces (Pt[11,7,1] and Pt[841]) have been investigated and both the magnitude and potential dependence of the enantioselective electro-oxidation of glucose characterised. Additionally, the changes engendered by interchanging the character of the two steps whose confluence form the kink whilst maintaining the symmetry of the terrace has also been examined via a comparison of Pt[643] and Pt[431]. Low energy electron diffraction (LEED) was used to confirm that all surfaces when clean and thermally annealed were in their (1 x 1) state. Cyclic voltammetry (CV) confirmed this finding for flame-annealed electrodes after cooling in hydrogen. Three general points emerge from the electro-oxidation studies: (i) The highest degree of enantioselectivity is exhibited by kink sites adjacent to [111] and [110] terraces in sulfuric acid. (ii) The adsorption of specifically adsorbed anions like bisulfate/sulfate influences strongly the chiral discriminatory behaviour of all surfaces. (iii) No electro-oxidation takes place at [110] sites, as evidenced by complete overlap of the [110] step hydrogen underpotential deposition (UPD) charge in glucose and glucose-free solutions. Nonetheless it is deduced that [110] sites must play some part in the initial orienting of the glucose molecule prior to reaction. Ideas based on these findings are developed in order to rationalise in particular the influence of anion adsorption on the initial enantioselective interaction of the glucose molecule with the chiral surface.     

Direct Asymmetric Mannich‐Type Reaction of α‐Isocyanoacetates with Ketimines using Cinchona Alkaloid/Copper(II) Catalysts

The enantioselective direct Mannich‐type reaction of ketimines with α‐isocyanoacetates has been developed. Excellent yields and enantioselectivity were observed for the reaction of various ketimines and α‐isocyanoacetates using cinchona alkaloid/Cu(OTf)₂ and a base. Both enantiomers of the products could be obtained by using pseudoenantiomeric chiral catalysts. This process offers an efficient route for the synthesis of α,β‐diamino acids.     

Enantioselective palladium-catalyzed total synthesis of vitamin e by employing a domino Wacker-Heck reaction

An enantioselective total synthesis of vitamin E in which a novel palladium-catalyzed domino reaction was employed as the key step is described. This reaction allows the formation of the chiral chroman framework and the concurrent introduction of part of the side chain of vitamin E. The sequence comprises an enantioselective Wacker cyclization and a subsequent Heck reaction. Accordingly, reaction of alkenylphenol 12 with methyl vinyl ketone (13) in the presence of catalytic amounts of Pd(OTFA)(2) (TFA = trifluoroacetate), the enantiopure ligand (S,S)-Bn-BOXAX (8 b; Bn = benzyl, BOXAX = 2,2'-bis(oxazolyl)-1,1'-binaphthyl, and p-benzoquinone (9) as an oxidant gives access to chiral chroman 10 with an enantioselectivity of 97 % ee in 84 % yield. Chroman 10 is then converted into 24 by an aldol condensation reaction with (3R)-3,7-dimethyloctanal (11). Subsequent 1,2-addition of methyllithium, elimination of water, and hydrogenation yields vitamin E.     

负载(S)-脯氨酸手性固相催化剂制备和在不对称加氢反应中的应用

用亲水性、高比表面积、硅烷化硅小球担载钯,以（Ｓ）－脯氨酸为手性助剂、苯乙酮为反应底物,考察不对称加氢反应和不同有机碱助催化剂的影响。实验表明,当使用三辛胺助催化剂时,（Ｒ）－苯乙醇的对映异构体选择性可达１７．５％。将（Ｓ）－脯氨酸负载于亲水性、高比表面积、硅烷化硅小球担体表面,以Ｐｄ（ＯＡｃ）２为催经剂前体,制备负载型手性固相催化剂,初步考察了（Ｓ）－脯氨酸与中心金属钯的摩尔比、疏水性不同的有机     

Enantiospecific electrodeposition of chiral CuO films on single-crystal Cu(111)

Epitaxial films of monoclinic CuO have been electrodeposited on single-crystal Cu(111) from solutions containing either (S,S)- or (R,R)-tartrate. X-ray pole figure analysis reveals that the CuO film grown from (S,S)-tartrate exhibits a (1) out-of-plane orientation while the film grown from (R,R)-tartrate has a (11) orientation. Even though CuO does not crystallize within a chiral space group, the orientations obtained exhibit a surface chirality similar to that obtained from high index fcc metal surfaces. The films were shown to be enantioselective toward the catalytic oxidation of tartrate molecules by cyclic voltammetry. The technique should prove to be applicable to the electrodeposition of chiral surfaces of other low-symmetry materials on achiral substrates and should prove to be of use to those interested in the synthesis, separation, and detection of chiral molecules.     

Enantioselective oxidation of olefins catalyzed by chiral copper bis(oxazolinyl)pyridine complexes: a reassessment

Copper complexes of chiral tridentate pybox ligands synthesized using a modified procedure have been studied as catalysts for the enantioselective allylic oxidation of olefins. A variety of olefins have been used in this reaction. Using 5 mol% of a Cu(II) complex of the tridentate pybox ligand, phenylhydrazine, and tert-butyl perbenzoate as oxidant in acetone, optically active allylic benzoates were obtained up to 94% ee in few hours. It was also observed that the use of molecular sieves in the reaction did not alter the enantioselectivity. Temperature was found to be very crucial in rate of the enantioselective allylic oxidation of olefins. Using EPR spectra, it has been shown that the Cu(II) species is reduced to Cu(I) by phenylhydrazine and phenylhydrazone, but the reduction with the former is faster in comparison to the latter. It was concluded that the rate enhancement was not specific to the presence of phenylhydrazine or phenylhydrazone, but both were equally responsible provided acetone was used as a solvent.     

Cu(I)-catalyzed direct enantioselective cross aldol-type reaction of acetonitrile

Direct catalytic enantioselective cross aldol-type reaction of an acetate surrogate was developed using Cu alkoxide-chiral phosphine complexes as catalysts. Chemoselective activation and deprotonation of the donor substrate (acetonitrile) by the soft metal alkoxide in a strongly donating solvent (HMPA) are key to success in this reaction. Useful chemical yields and promising enantioselectivities are produced using either DTBM-SEGPHOS or a tuned BIPHEP as a chiral ligand. [reaction: see text]     

Aspects of enantioselective heterogeneous catalysis: structure and reactivity of (S)-(-)-1-(1-naphthyl)ethylamine on Pt[111

The molecular orientation, spatial distribution, and thermal behavior of the powerful chiral catalyst modifier precursor (S)-naphthylethylamine adsorbed on Pt[111] have been studied by NEXAFS, XPS, STM, and temperature programmed reaction. At 300 K, both in the presence and in the absence of coadsorbed hydrogen, the strongly tilted molecules do not form ordered arrays. These results constitute the first direct evidence against the template model and are at least consistent with the 1:1 interaction model of chiral induction in the enantioselective hydrogenation of alkyl pyruvates. Raising the temperature beyond 320 K (the temperature of enantioselectivity collapse) leads either to irreversible dimerization with hydrogen elimination or to dissociation of the ethylamine moiety, depending on whether coadsorbed H(a) is present. Either way, the stereogenic center is destroyed. These findings provide the first direct clue as to the possible origin of enantioselectivity collapse, by a mechanism not previously considered. When NEA and methyl pyruvate are coadsorbed in the presence of H(a), STM reveals entities that could correspond to a 1:1 docking complex between the prochiral reactant and the chiral modifier.     

Mechanistic insights into the proline-directed enantioselective heterogeneous hydrogenation of isophorone

The adsorption rates onto a range of platinum single-crystal surfaces of key species involved in the proline-directed heterogeneous enantioselective hydrogenation of isophorone were investigated by electrochemical means. Specifically, the uptakes of the prochiral reactant (isophorone), the chiral hydrogenation product (3,3,5-trimethylcyclohexanone), and the chiral directing agent ((R)- and (S)-proline) were examined. The effects of R,S chiral kink sites on the adsorption of (R,S)-proline were also studied. The reactant adsorbs approximately 105 times faster than the chiral modifier so that under conditions of competitive adsorption the latter is entirely excluded from the metal surface. Supplementary displacement and reaction rate measurements carried out with practical Pd/carbon catalysts show that under certain reaction conditions isophorone quickly displaces preadsorbed proline from the metal surface. Thus both kinetics and thermodynamics ensure that the chiral modifier can play no role in any surface-mediated process that leads to enantiodifferentiation. These results are fully consistent with the recent proposal1 that the crucial step leading to enantiodifferentiation occurs in the solution phase and not at the metal surface. In addition, it is found that there is no preferred diastereomeric interaction between (R,S)-proline and R,S step kink sites on Pt{643} and Pt{976}, implying that such sites do not play a role in determining the catalytic behavior of supported metal nanoparticles.     

Enantioselective conjugate addition of dialkylzinc and diphenylzinc to enones catalyzed by a chiral copper(I) binaphthylthiophosphoramide or binaphthylselenophosphoramide ligand system

The enantioselective conjugate addition of dialkylzinc or diphenylzinc to enones was catalyzed by a copper(I)-axially chiral binaphthylthiophosphoramide or binaphthylselenophosphoramide ligand system at room temperature (20 degrees C) or 0 degrees C, affording the Michael adducts in high yields with excellent ee for cyclic and acyclic enones. The enantioselectivity and reaction rate achieved here are one of the best results yet for the Cu-catalyzed conjugate addition to enones. It was revealed that this series of chiral phosphoramides was a novel type of S,N-bidentate ligands on the basis of (31)P NMR and (13)C NMR spectroscopic investigations. The mechanism of this asymmetric conjugate addition system has been investigated as well. We found that the acidic proton of phosphoramide in these chiral ligands play a significant role in the formation of the active species. A bimetallic catalytic process has been proposed on the basis of previous literature. The linear effect of product ee and ligand ee further revealed that the active species is a monomeric Cu(I) complex bearing a single ligand [Cu(I):ligand 1:1].     

Asymmetric Henry reaction catalyzed by C2-symmetric tridentate bis(oxazoline) and bis(thiazoline) complexes: metal-controlled reversal of enantioselectivity

[reaction: see text] C(2)-symmetric tridentate bis(oxazoline) and bis(thiazoline) ligands with a diphenylamine backbone have been investigated in the catalytic asymmetric Henry reaction of alpha-keto esters with different Lewis acids. Their Cu(OTf)(2) complexes furnished S enantiomers, while Et(2)Zn complexes afforded R enantiomers, both of them with higher enantioselectivities (up to 85% ee). Reversal of enantioselectivity in asymmetric Henry reactions was achieved with the same chiral ligand by changing the Lewis acid center from Cu(II) to Zn(II). The results show that the NH group in C(2)-symmetric tridentate chiral ligands plays a very important role in controlling both the yields and enantiofacial selectivity of the Henry products.     

Asymmetric hydrolytic kinetic resolution with recyclable macrocyclic Co(III)-salen complexes: a practical strategy in the preparation of (R)-mexiletine and (S)-propranolol

A chiral cobalt(III) complex (1e) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1R,2R-(-)-1,2-diaminocyclohexane with trigol bis-aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47% with respect to the epoxides, 53% with respect to the diols) and high enantioselectivity (ee>99% for the epoxides, up to 96% for the diols) were achieved in 2.5-16 h. The Co(III) macrocyclic salen complex (1e) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules (R)-mexiletine and (S)-propranolol.