Iridium complexes relevant to the catalytic enantioselective hydrogenation of 2-methyl-6-ethylphenyl-1'-methyl-2'-methoxyethylimine (MEA-imine, 1) in the Syngenta Metolachlor (3) process were prepared and characterized. Reaction of the diphosphane (S)-1-[(R)-2-(diphenylphosphanyl)ferrocenyl]ethyldi(3,5-xylyl)phosphane ((S)-(R)-Xyliphos, (S)-(R)-4) with [Ir(2)(micro-Cl)(2)(cod)(2)] (cod=1,5-cyclooctadiene) afforded [Ir(Cl)(cod)[(S)-(R)-4]] (7), which reacted with AgBF(4) to form [Ir(cod)[(S)-(R)-4]]BF(4) (8). Complexes 7 and 8 reacted with iodide to yield [Ir(I)(cod)[(S)-(R)-4]] (9). When 9 was treated with one and two equivalents of HBF(4), two isomers of the cationic Ir(III) iodo hydrido complex [Ir(I)(H)(cod)[(S)-(R)-4]]BF(4) were solated (10 and 11, respectively). Complex 9 was oxidized with one equivalent of I(2) to give the iodo-bridged dinuclear species [Ir(2)I(2)(micro-I)(3)[(S)-(R)-4](2))]I (12). [Ir(2)(micro-Cl)(2)(coe)(4)] (coe=cyclooctene) reacted with (S)-(R)-4 to yield the chloro-bridged dinuclear complex [Ir(2)(micro-Cl)(2)[(S)-(R)-4](2)] (13). Complexes 7-12 were structurally characterized by single-crystal X-ray diffraction and tested as single-component catalyst precursors for enantioselective hydrogenation of MEA-imine. Complex 10 and dinuclear complex 12 gave the best catalytic results. Efforts were also directed at isolating substrate- or product-catalyst adducts: Treatment of 8 with 2,6-dimethylphenyl-1'-methyl-2'-methoxyethylimine (DMA-imine, 14, a model for 1) under H(2) allowed four isomers of [Ir(H)(2)[(S)-(R)-4](14)]BF(4) (18-21) to be isolated. These analytically pure isomers were fully characterized by 2D NMR techniques. X-ray structural analysis of an Ir(I)-imine adduct, namely, [Ir(C(2)H(4))(2)(14)]BF(4) (25), which was prepared by reacting [IrCl(C(2)H(4))(4)] with [Ag(14)(2)]BF(4) (16), confirmed the kappa(2) coordination mode of imine 14.
[reaction: see text] beta-Ketoesters can be effectively monofluorinated with F-TEDA using CpTiCl(3) as a catalyst. With the use of this catalyst, the extent of the competing difluorination does not reach 10%. [TiCl(2)(TADDOLato)] complexes catalyze the one-pot enantioselective heterodihalogenation of beta-ketoesters with F-TEDA and NCS to afford alpha-chloro-alpha-fluoro-beta-ketoesters in moderate to good yields. The sequence of addition of the halogenating agents determines the sense of chiral induction.
[RuCl2(PPh3)3] reacts with thallium(I) fluoride to give either [Tl(mu-F)3Ru(PPh3)3] (1) or [Tl(mu3-F)(mu2-Cl)2Ru2(mu2-Cl)(mu2-F)(PPh3)4] (2) depending on the excess of TlF used. Both 1 and 2 were fully characterized, including X-ray structure determinations. Complex 1 reacts with dihydrogen to form the known ruthenium hydride complex [Ru(H)2(H2)(PPh3)3] upon hydrogenolysis of the Ru-F bond. The reaction of 1 with activated alkyl bromides (R-Br) gives the corresponding alkyl fluorides and the trinuclear complex [Tl(mu3-F)(mu2-F)(mu2-X)Ru2(mu2-Br)(mu2-F)(PPh3)4] (X=Br, F) (3), whose structure closely resembles that of 2. However, 1 is not active as catalyst for the nucleophilic fluorination of R-Br in the presence of thallium fluoride. The effect of the bridging coordination mode of fluoride on the Ru-F bond is discussed in terms of the HSAB principle, which suggests a more general model for predicting the stability of d6 and d8 complexes containing hard ligands (such as fluoro, oxo, and amido).
Aryl azole scaffolds are present in a wide range of pharmaceutically relevant molecules. Their ortho-selective metalation at the aryl ring is challenging, due to the competitive metalation of the more acidic heterocycle. Seeking a practical access to a key Active Pharmaceutical Ingredient (API) intermediate currently in development, we investigated the metalation of 1-aryl-1H-1,2,3-triazoles and other related heterocycles with sterically hindered metal-amide bases. We report here a room temperature and highly regioselective ortho-magnesiation of several aryl azoles using a tailored magnesium amide, TMPMgBu (TMP = 2,2,6,6-tetramethylpiperidyl) in hydrocarbon solvents followed by an efficient Pd-catalyzed arylation. This scalable and selective reaction allows variation of the initial substitution pattern of the aryl ring, the nature of the azole moiety, as well as the nature of the electrophile. This versatile method can be applied to the synthesis of bioactive azole derivatives and complements existing metal-mediated ortho-functionalizations.
Iridium complexes of DMA-imine [2,6-dimethylphenyl-1'-methyl-2'-methoxyethylimine, 1 a) and (R)-DMA-amine [(1'R)-2,6-dimethylphenyl-1'-methyl-2'-methoxyethylamine, 2 a] that are relevant to the catalytic imine hydrogenation step of the Syngenta (S)-Metolachlor process were synthesized: metathetical exchange of [Ir2Cl2(cod)2] (cod=1,5-cyclooctadiene) with [Ag(1 a)2]BF4 and [Ag((R)-2 a)2]BF4 afforded [Ir(cod)(kappa2- -1 a)]BF4 (11) and [Ir(cod)(kappa2-(R)-2 a)]BF4 ((R)-19)), respectively. These complexes were then used in stopped-flow experiments to study the displacement of amine 2 a from complex 19 by imine 1 a to form the imine complex 11, thus modeling the product/substrate exchange step in the catalytic cycle. The data suggest a two-step associative mechanism characterized by k1=(2.6+/-0.3) x 10(2) M(-1) s(-1) and k2=(4.3+/-0.6) x 10(-2) s(-1) with the respective activation energies EA1=(7.5+/-0.6) kJ mol(-1) and EA2=(37+/-3) kJ mol(-1). Furthermore, complex 11 reacted with H2O to afford the hydrolysis product [Ir(cod)(eta(6-)-2,6-dimethylaniline)]BF4 (12), and with I2 to liberate quantitatively the DMA-iminium salt 14. On the other hand, the chiral amine complex (R)-19 formed the optically inactive eta6-bound compound [Ir(cod)(eta6-rac-2 a)]BF4 (rac-18) upon dissolution in THF at room temperature, presumably via intramolecular C-H activation. This racemization was found to be a two-step event with k'1=9.0 x 10(-4) s(-1) and k2=2.89 x 10(-5) s(-1), featuring an optically active intermediate prior to sp3 C-H activation. Compounds 11, 12, rac-18, and (R)-19 were structurally characterized by single-crystal X-ray analyses.
The preparation of two new chiral, enantiopure, and conformationally constrained phosphocin and 1,5-diphosphocin, incorporating two ferrocenyl units, is described. The gold(I) chloride complexes of these ligands and (S)-(R)-PPF-OMe were prepared, and their structures, in solution and solid states, are compared. Abstraction of the chloride anion by the addition of silver salt of either toluenesulfonate or chiral BINOL-phosphates generates active catalysts for the intramolecular cyclization of 6-methyl-1,1-diphenylhepta-4,5-dien-1-ol, where up to 47% ee can be obtained. Match and mismatch effects between chiral ligands and counteranions are highlighted.
The straightforward, high-yield synthesis and X-ray structural analysis of the air-stable planar-chiral bis(ferrocenyl)carbene 1,3-bis-{(1R)-1-[(1R)-1-(trimethylsilyl)ferrocen-2-yl]ethyl}imidazol-2-ylidene (5) is reported. Compound 5 is obtained in four steps from the amine [(1R)-1-(dimethylamino)ethyl]ferrocene (1) upon diastereoselective silylation, methylation, nucleophilic substitution by imidazole, and deprotonation. The X-ray crystal structure of the free carbene shows the typical conformational features of the 1,2-disubstituted ferrocenyl units, as found in other ferrocenyl ligands derived from 1. 1. Introduction. ± Stable N-heterocyclic carbenes (NHCs) [1] [2], mostly bearing bulky substituents at the N-atoms, are becoming ubiquitous ligands in organometallic chemistry [3] and homogeneous catalysis [4 ± 11] as phosphine substitutes [12]. However, chiral enantiomerically pure derivatives are still quite rare, and only a very limited number of applications have been reported [13 ± 17]. Furthermore, chiral ferrocenyl derivatives have proven very successful in asymmetric catalysis, as ligands often displaying both central and planar chirality, because of their great synthetic versatility [18]. These two observations prompted us to develop a simple synthesis of a ferrocenebased carbene for use as a monodentate ligand in asymmetric catalysis. We reasoned that such a preparation should start from a readily available chiral ferrocene derivative that would also be set up for a modular construction of possibly a range of related compounds. Most sensibly, this starting material should be the amine 1 ([(1R)-1-(dimethylamino)ethyl]ferrocene, Scheme) because of both its typical diastereoselective ortho-lithiation chemistry and the ease of nucleophilic replacement of the amino group by a variety of nucleophiles. Very recently, Bolm et al. reported a more elaborate preparation of a monoferrocenyl carbene starting from a chiral ferrocenyl sulfoxide [19].
The complexes [TiCl 2 {(R,R)-TADDOLato}(DME)] ¥ MeCN (3), and [TiCl 2 {(R,R)-1-Nph-TADDOLato}(MeCN) 2 ] ¥ CH 2 Cl 2 (4b) (DME 1,2-dimethoxyethane; (R,R)-TADDOLato (4R,5R)-2,2-dimethyla,a,a',a'-tetraphenyl-1,3-dioxolane-4,5-dimethanolato(2 À)-kO,kO';(R,R)-1-Nph-TADDOLato (4R,5R)-2,2-dimethyl-a,a,a',a'-tetra(naphthalen-1-yl)-1,3-dioxolane-4,5-dimethanolato(2 À)-kO,kO') were prepared and isolated in high yield as stable crystalline materials (Scheme 1). They constitute ideally suited and easyto-handle catalyst precursors for a large number of Ti-catalyzed asymmetric reactions, for which they have been previously generated in situ. The X-ray crystal structures of 3 and 4b show a distorted octahedral geometry around Ti with the chloro ligands in mutual trans positions (Figs. 5 and 6). The new chiral diols a-(1S,3R)-3-hydroxy-2,2,3-trimethylcyclopentyl]-a-phenylbenzenemethanol (13a), derived from camphoric acid (5), and (M)-6,6'-dimethyl-a,a,a',a'-tetraphenyl[1,1'-biphenyl]-2,2'-dimethanol (15) were prepared (Schemes 3 and 4). These new ligands are able to form mononuclear complexes with the Ti IV Cl 2 fragment. The corresponding complex 14 derived from 13a was characterized by X-ray as a mixed THF/MeCN adduct. 1. Introduction. ± Complexes of the general formula [TiCl 2 (OR) 2 ] serve as Lewis acid catalysts or mediators (i.e., in stoichiometric amounts) in allylation reactions of aldehydes in the presence of allylstannanes, hetero-Diels-Alder reactions, ene reactions, Michael additions, Mukaiyama silyl-aldol condensations, and other reactions (see review [1]). Of particular interest are those complexes derived from an enantiomerically pure chelating diol. Thus, [TiCl 2 (BINOLato)] complexes (BINOLato [1,1'-binaphthalene]-2,2'-diolato(2 À)-kO,kO') have found specific use in enantioselective Mukaiyama aldol reactions [2], cyanosilylation of aldehydes [2], carbonyl-ene reactions [3], carbonyl allylsilane or allylstannane additions [4 ± 6], ene cyclizations [7], (hetero)-Diels-Alder reactions [8], and others (for a review, see [9]). Complexes of the type [TiCl 2 (TADDOLato)] 1 ) serve as catalysts in enantioselective cyanosilylations [10], (hetero)-Diels-Alder [11 ± 15], [2 2] cycloadditions [16 ± 18], [2 3] cycloadditions [19], 1,3-dipolar cycloadditions [20], nitro-aldol reactions [21], fluorinations [22], and others (for reviews, see [9] [23]).When inspecting the procedures for the generation of the titanium catalysts used in the reactions mentioned above, one notes that they are prepared in situ according to
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