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.     

Using a tripod as a chiral chelating ligand: chemical exchange between equivalent molecular structures in palladium catalysis with 1,1,1-tris(oxazolinyl)ethane ("trisox")

Threefold symmetrical chiral podands may simplify the stereochemistry of key catalytic intermediates for cases in which they only act as bidentate ligands. This applies to systems in which chemical exchange between the different kappa2-coordinated forms takes place and in which the non-coordinated sidearm may play a direct or indirect role at some earlier or later stage in the catalytic cycle. Palladium(II)-catalysed allylic substitutions provide appropriate test reactions along these lines. A series of neutral dichloropalladium(II) complexes, [PdCl2(iPr-trisox)] (1a), [PdCl2(Ph-trisox)] (1b), [PdCl2(Bn-trisox)] (1c) and [PdCl2(Ind-trisox)] (1d) (trisox=1,1,1-tris(oxazolinyl)ethane) were synthesised by reaction of the respective trisox derivative with [PdCl2(PhCN)2] and characterised inter alia by 15N NMR spectroscopy. Direct detection of the heteronuclei without isotope enrichment and with "normal" sample concentrations was achieved with the aid of a cryogenically cooled NMR probe on a 600 MHz NMR spectrometer. Whereas the 15N nuclei of the coordinated oxazoline rings resonate at delta=160-167 ppm and appear as two singlets due to their diastereotopicity, the signal assigned to the dangling oxazoline "arm" is observed at delta=238-240 ppm. Variable-temperature NMR studies along with a systematic series of magnetisation transfer experiments established exchange between ligating and non-ligating oxazoline rings. Reaction of [Pd(allyl)(cod)]BF4 (cod=cyclooctadiene) with Ph-trisox in CH(2)Cl(2) gave the corresponding allyl complex 2, for which fast exchange between the three oxazoline heterocycles as well as between the exo and endo diastereomers was observed along with a very slow eta3-eta1-eta3 process of the allyl fragment (magnetisation transfer). Palladium(0) complexes were prepared by reaction of trisox derivatives or sidearm-functionalised BOX (BOX=bis(oxazolinyl)dimethylmethane) ligands with [Pd(nbd)(alkene)] (nbd=norbornadiene, alkene=maleic anhydride or tetracyanoethylene). X-ray diffraction studies of the iPr-trisox and Ph-trisox complexes (3a and 3b) established Y-shaped trigonal planar coordination geometries with the trisox ligand coordinated in a bidentate fashion, whilst the pi-coordinated maleic anhydride ligand adopts one of the two possible diastereotopic orientations. As the catalytic test reaction, the allylic alkylation of 1,3-diphenylprop-2-enyl acetate substrate with dimethyl malonate as nucleophile (in the presence of N,O-bis(trimethylsilyl)acetamide) was investigated for the trisox derivatives, their BOX analogues, and a series of less symmetric "sidearm" functionalised bisoxazolines. The trisoxazoline-based catalysts generally induce a better enantioselectivity compared to their bisoxazoline analogues and display significant reduction of the induction period as well as rate enhancement.     

Shaping and enforcing coordination spheres: the implications of C3 and C1 chirality in the coordination chemistry of 1,1,1-tris(oxazolinyl)ethane ("trisox")

A key feature of tris(oxazolinyl)ethane ("trisox") ligands, which have shown broad scope in asymmetric catalysis, is the orientation and steric demand of their oxazoline substituents. This, along with the modularity of their synthesis determines their coordination chemistry. The possibility to combine oxazolines, in which the stereogenic centers adjacent to the N-donor atoms have different absolute configuration, whilst retaining their ability to coordinate as tripodal ligands, has been demonstrated by the synthesis of the enantiomerically pure C3-symmetric iPr-trisox(S,S,S) and C1-symmetric iPr-trisox(S,S,R) and their reaction with [Mo(CO)3(NCMe)3] yielding [Mo{iPr-trisox(S,S,S)}(CO)3] (1 a) and [Mo{iPr-trisox(S,S,R)}(CO)3] (1 b), respectively. The non-autocomplementarity of two homochiral trisox ligands at one metal center has been demonstrated by reaction of rac-C3 iPr-trisox with one equivalent of [Co(ClO4)2].6 H2O, giving the centrosymmetric heterochiral complex [Co(iPr-trisox)2](ClO4)2 (3), whereas an analogous reaction with the enantiopure ligand yielded a mixture of Co(II) complexes, which is characterized by the total absence of a [(trisox)2Co](+/2+) ion. The scope of the trisox ligand in terms of facial coordination to both early and late transition metals was demonstrated by the synthesis and structural characterization of the mononuclear complexes [ScCl3(iPr-trisox)] (4), [Fe(tBu-trisox)(NCMe)3](BF4)2 (5), and [Ru(eta6-p-cymene)(iPr-trisox)](PF6)2 (6). The facial coordination of their three ligating atoms to a metal center may be impeded if the transition-metal center stereoelectronically strongly favors a non-deltahedral coordination sphere, which is generally the case for the heavier d8-transition-metal atoms/ions. Reaction of iPr-trisox with [Rh(cod)2]BF4 led to the formation of the 16-electron d8-configured complex [Rh(iPr-trisox)(cod)](BF4) (7), which is oxidized by CsBr3 to give the Rh(III) complex [RhBr3(iPr-trisox)] (8) possessing a C3-symmetric structure with a kappa3-N-trisox ligand. The crystalline salts [M2(mu-Cl3)(iPr-trisox)2](PF6) (M=Fe(II): 9, Co(II): 10, Ni(II): 11), were prepared by addition of one molar equivalent of iPr-trisox and an excess of KPF6 to solutions of the anhydrous (FeCl2) or hydrated metal halides (CoCl2.6 H2O, NiCl2.6 H2O). All dinuclear complexes display weak magnetic coupling. For the mononuclear species [CuCl2(iPr-trisox)] (12) the removal of a chloride anion and thus the generation of a dinuclear chloro-bridged structure failed due to Jahn-Teller destabilization of a potential octahedral coordination sphere.     

Multiple catalysis with two chiral units: an additional dimension for asymmetric synthesis

This Minireview focuses on asymmetric reactions mediated by two distinct chiral catalysts (chiral multiple catalysis). Initially, this approach appears unconventional, but indeed it allows a fast multidimensional optimization and fine-tuning of the catalytic system required to perform a given transformation. Herein, this emerging concept is presented and its potential applications are highlighted.     

Bis(oxazolinyl)phenyl transition metal complexes: synthesis, asymmetric catalysis, and coordination chemistry

Molecular catalysts for organic synthesis should be constructed to be tailored to target reactions and their desirable conditions. In our search for them, we have studied new types of transition metal molecular catalysts dressed with a tridentate N,C,N modular ligand, which consists of a C2-symmetric side-by-side phenyl group with chiral bis(oxazolinyl) substituents. The ligand, 2,6-bis(oxazolinyl)phenyl abbreviated as Phebox, can connect covalently to transition metals by the central carbon atom. Here, we review our recent work on the chemistry of Phebox and its metal complexes, including preparation, structural analysis, asymmetric Lewis acid catalysis, asymmetric hydrosilylation, asymmetric conjugate reduction, asymmetric reductive aldol reaction, and organometallic reactions.     

Recent applications of chiral ferrocene ligands in asymmetric catalysis

Despite the impressive progress achieved in asymmetric catalysis during the last decade, an increasing number of new catalysts, ligands, and applications are reported every year to satisfy the need to embrace a wider range of reactions and to improve the efficiency of existing processes. Because of their availability, unique stereochemical aspects, and wide variety of coordination modes and possibilities for the fine-tuning of the steric and electronic properties, ferrocene-based ligands constitute one of the most versatile ligand architectures in the current scenario of asymmetric catalysis. Over the last few years ferrocene catalysts have been successfully applied in an amazing variety of enantioselective processes. This Review documents these recent advances, with special emphasis on the most innovative asymmetric processes and the development of novel, efficient types of ferrocene ligands.     

Transition‐Metal‐Catalyzed Enantioselective [2+2+2] Cycloadditions for the Synthesis of Axially Chiral Biaryls

Tying up loose ends : Recent advances towards a development of novel transition‐metal‐catalyzed enantioselective [2+2+2] cycloadditions for the synthesis of biaryls are summarized in this Focus Review. Additionally, the enantioselective synthesis of axially chiral biaryls possessing non‐biaryl axial chirality is also presented. These novel asymmetric aromatization reactions allow the production of various axially chiral biaryl compounds with high enantioselectivity.

     

Construction and utilisation of planar graphs of two series of IPR fullerenes through the use of threefold rotational symmetry

Threefold rotational symmetry has been used to develop an algorithm for the construction of planar graphs of IPR fullerenes and to factorize their characteristic polynomials. Two series of fullerenes of the formula C_60+12n and C_60+18n have thus been obtained. The algorithm has been shown to be useful for predicting the nature of variation of the point groups of the fullerenes with increased n, for counting the number of ¹³C nuclear magnetic resonance (NMR) signals (along with their relative intensities), and also for obtaining a large part of their eigenspectra. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Recent developments in enantioselective gold(I) catalysis

The use of gold(I) complexes as catalysts for organic transformations has become increasingly common over the past decade, leading to the development of a number of useful carbon-carbon and carbon-heteroatom bond-forming processes. In contrast, enantioselective catalysis employing gold(I) complexes was, until recently, exceedingly rare, due in large part to the pronounced tendency of gold(I) to form linear, two-coordinate complexes. However, new approaches and strategies have emerged over the past two years, leading to the development of a number of effective gold(I)-catalyzed enantioselective transformations, most notably the enantioselective hydrofunctionalization of allenes. Outlined herein is an overview of enantioselective gold(I) catalysis since 2005.     

手性氨基醇在不对称催化中的应用及新进展

综述了手性氨基醇作为配体或催化剂在不对称合成中的应用及最新进展。     

Controlling stereochemical outcomes of asymmetric processes by catalyst remote molecular functionalizations: chiral diamino-oligothiophenes (DATs) as ligands in asymmetric catalysis

The synthesis, characterization, and structure-guided application of a new class of highly versatile chiral C(2)-symmetric diamine-oligothiophene ligands in Pd-catalyzed asymmetric transformations are presented. Experimental investigations of the intimate role of pendant pi-conjugate oligothiophenes in determining the catalytic activity of the corresponding chiral Pd complexes are described. Their unusual behavior opens up new routes toward the logical design of finely tuned organometallic catalysts by remote structural functionalizations.     

Recent developments in the catalytic asymmetric synthesis of alpha- and beta-amino acids

The stereoselective synthesis of amino acids is of great importance for the construction of optically active natural products and pharmaceuticals. Apart from enzymes, a broad repertoire of chiral reagents, auxiliaries, and catalysts can be used for the formation of amino acids. Asymmetric reactions using catalytic amounts of chiral molecules provide efficient methods for the generation of optically active proteinogenic and nonproteinogenic amino acids. This minireview collects recent work on catalytic asymmetric synthesis of alpha- and beta-amino acids.