Reaction between benzyllithium and 2-ethylpyridine: chiral crystals of a 1-(2-pyridyl)ethyllithium complex versus formation of lithium 4-benzyl-2-ethyl-1,4-dihydropyridinide

Abstract  

The reaction between benzyllithium and prochiral 2-ethylpyridine in tetrahydrofuran has been studied. In the presence of N,N,N′,N′′,N′′-pentamethyldiethylenetriamine (PMDTA), it was found that 1-(2-pyridyl)ethyllithium was formed as a PMDTA complex. This complex is mononuclear, with lithium coordinated to the pyridyl nitrogen atom only; there are no short lithium–carbon distances and the structure approaches that of an enamide rather than a carbanion. The complex undergoes spontaneous resolution and forms chiral crystals with two molecules in the asymmetric unit; the two molecules have different configurations at the chirogenic pyridyl nitrogen atoms but share the same chiral conformation of the chelate ring systems. Reaction between benzyllithium and 2-ethylpyridine in tetrahydrofuran in the absence of PMDTA was found to give a high proportion of lithium 4-benzyl-2-ethyl-1,4-dihydropyridinide, and crystals of a dinuclear complex displaying tetrahydrofuran ligands and co-crystallised n-hexane molecules were isolated.     

Molecular modeling of salt (lithium chloride) effects on the enantioselectivity of diethylzinc addition to benzaldehyde in the presence of chiral beta-amino alcohols

Beta-amino alcohols (S,S,S)-1 and (R,R,S)-1, derived from cyclohexene oxide and containing alpha-phenylethyl auxiliaries, were examined as chiral promoters in the addition of diethylzinc to benzaldehyde. In agreement with literature precedent, the N-alpha-phenylethyl chiral auxiliary had no significant impact on enantioinduction, which is determined by the configuration of the framework's C(OH), with unlike induction. Contrary to some literature reports, stereoinduction by lithium salt derivatives of (S,S,S)-1 and (R,R,S)-1 was lower than that obtained with the free amino alcohol. Remarkable lithium chloride salt effects were observed in the reaction. In particular, an opposite chiral induction was found with (S,S,S)-1-Li(2) as ligand and in the presence of "inert" salt. N-Alkylated derivatives (S,S,S)-3-7 proved to be more efficient ligands, providing higher yields and enantioselectivities in the formation of carbinols (R)- or (S)-2. BP86/DN**//PM3 theoretical calculations proved remarkably successful in reproducing the experimental observations and permitted expansion of Noyori's catalytic cycle [J. Am. Chem. Soc. 1995, 117, 6327] to understand the relevant N-substitution and medium salt effects that determine the enantioselection in this catalytic asymmetric reaction.     

Chiral rodlike platinum complexes, double helical chains, and potential asymmetric hydrogenation ligand based on "linear" building blocks: 1,8,9,16-tetrahydroxytetraphenylene and 1,8,9,16-tetrakis(diphenylphosphino)tetraphenylene

This paper is concerned with the synthesis of 1,8,9,16-tetrahydroxytetraphenylene (3a) via copper(II)-mediated oxidative coupling, its resolution to optical antipodes, and its conversion to 1,8,9,16-tetrakis(diphenylphosphino)tetraphenylene (3b). On the basis of these chiral "linear" building blocks, three rodlike chiral complexes, triblock (R,R,R,R)-17 and (S,S,S,S)-20 and pentablock (R,R,R,R,R,R,R,R)-22, were constructed. As a hydrogen bond donor, racemic and optically active 3a was allowed to assemble with linear acceptors to afford highly ordered structures. A 1:1 adduct of 4,4'-bipyridyl and (+/-)-3a exists in a dimeric form of 3a linked by 4,4'-bipyridyl through hydrogen bonds. Pyrazine serves as a short linker between achiral parallel chains each formed by (+/-)-3a, while self-assembly of homochiral 3a into alternate parallel chains occurs in the adduct of 5,5'-dipyrimidine with (+/-)-3a. Self-assembly of (S,S)-3a or (R,R)-3a with 4,4'-dipyridyl yielded a packing of chiral double helical chains formed by chiral tetrol 3a molecules. A novel chiral ligand, (S,S)-23, derived from 3a was used in the asymmetric catalytic hydrogenation of alpha-acetamidocinnamate, yielding up to 99.0% ee and 100% conversion.     

Soluble Ni alkoxides based on dimethylaminoisopropoxide ligands: molecular structure of [Li(PrOH)Ni (η-OR)2Cl]2 and of cis-NiCl2(ROH)2 (R = CHMeCH2NMe2)

Various routes to Ni^II aminoalkoxides have been investigated. A nickel isopropoxide derivative 1 was prepared by anodic dissolution of the metal in the presence of LiCl as electrolyte. Alcoholysis reactions of 1 with 1-dimethylamino-2-propanol afforded the homoleptic nickel(II) aminoalkoxide 2 together with a Ni---Li species 3. 2 was also obtained by metathesis reactions between sodium alkoxide and the nickel hexammine complex whereas the reaction between the latter and the aminoalcohol led to an halide solvate, cis-NiCl₂(η²-ROH)₂, 4. The various compounds were characterized by elemental analysis, FT-IR and UV-vis spectroscopies as well as by X-ray diffraction for 3 and 4. 3 corresponds to [Li(PrⁱOH)Ni(η²-OCHMeCH₂NMe₂)Cl]₂ and the overall structure can be seen as two [Ni(η²-OCHMeCH₂NMe₂)₂Cl]⁻ moieties assembled by Li(PrⁱOH)⁺. The lithium atom is 4-coordinate due to its interaction with the oxygen atoms of the aminoalkoxide ligands. Nickel is 5-coordinate with a distorted tetragonal pyramidal stereochemistry, one nitrogen being in the apical position. The metal displays a distorted octahedral surrounding for the NiCl₂ adduct 4. The bond distances vary in the order Ni---OR < Ni---N ≈ Ni---O(H)R < Ni---Cl for 3 and 4. The various compounds (except 1) are soluble in organic media.     

Stereoselectivity and chiral recognition in copper(I) olefin complexes with a chiral diamine

Trigonal copper(I) complexes of the chiral bidentate ligand (1S,2S)-N,N'-Bis-(mesitylmethyl)-1,2-diphenyl-1,2-ethanediamine ((S,S)-1) have been prepared with hydrocarbon olefins, as well as with allylic alcohols and ethers. The stereochemistry of the complexes has been investigated by 1H NMR spectroscopy and by combined quantum mechanics and molecular mechanics (QM/MM) computational methods. The coordinated chiral nitrogen atoms can display equal (R, R) or opposite (R, S) configuration, the latter being disfavored if steric hindrance is present above and below the coordination plane. Although the complexes exist as rapidly equilibrated mixtures of stereoisomers, one of these is often dominant, and prochiral olefins are coordinated with high enantioface selection. In addition, the [(S,S)-1]-Cu+ fragment selectively recognizes the R enantiomer of secondary allylic alcohols and ethers, as confirmed by the X-ray crystal structure analysis of the adduct with (R)-1-buten-3-ol. The reasons for the observed selectivities have been elucidated, and lead to some implications which are consistent with the enantioselection observed in catalytic cyclopropanation reactions promoted by copper complexes of the same ligand.     

Designer chiral quaternary ammonium bifluorides as an efficient catalyst for asymmetric nitroaldol reaction of silyl nitronates with aromatic aldehydes

Designer chiral quaternary ammonium bifluoride 1 has been prepared, and both its catalytic and its chiral efficiency have been clearly demonstrated by achieving the first catalytic asymmetric nitroaldol reaction of silyl nitronate with aldehydes. For instance, the reaction of trimethylsilyl nitronate 2 (R(1) = Me) with benzaldehyde (R(2) = Ph) in THF in the presence of (S,S)-1 (2 mol %) proceeded smoothly at -78 degrees C, giving the corresponding nitroaldol adduct 3 (R(1) = Me, R(2) = Ph) in 92% isolated yield (anti/syn = 92:8) with 95% ee (anti isomer). The method was found to be successfully applicable to other aromatic aldehydes and silyl nitronates, and a high level of anti selectivity and enantiomeric excess was constantly observed. This finding should lead to the further development of fluoride ion-catalyzed asymmetric carbon-carbon bond-forming reactions.     

Structure/reactivity studies on an alpha-lithiated benzylsilane: chemical interpretation of experimental charge density

Modern organic synthesis (e.g., of natural products) is virtually impossible without employment of enantiomerically enriched compounds. In many cases, alkyllithium compounds are key intermediates for the generation of these stereogenic substances. In recent years, the lithiated carbon atom in silicon-substituted benzyllithium compounds has become a focus of interest because it is possible to maintain its stereogenic information. Starting from a highly enantiomerically enriched benzylsilane, (R,S)-2 x quinuclidine could be obtained, and the absolute configuration at the metalated carbon atom was determined by X-ray diffraction analysis. In solution, a quartet was found in the (13)C NMR spectrum for the metalated carbon atom because of coupling between carbon and lithium, indicating a fixed lithium carbon contact at room temperature. After reaction of (R,S)-2 x quinuclidine with trimethylchlorostannane, the trapped product (S,S)-4 was obtained with a dr > or = 98:2 with inversion of the configuration at the metalated carbon. Multipole refinement against high-resolution diffraction data and subsequent topological analysis of the benchmark system (R,S)-2 x quinuclidine provide insight in the electronic situation and thus the observed stereochemical course of the transformations. Surprisingly, the negative charge generated at the carbanion hardly couples into the phenyl ring. The neighboring silicon atom counterbalances this charge by a pronounced positive charge. Therefore, the alpha-effect of the silicon atom is caused not just by a polarization of the electron density but also by an electrostatic bond reinforcement. Furthermore, the experimentally determined electrostatic potential unequivocally explains the observed back side attack of an electrophile under inversion of the stereogenic center with high diastereomeric ratios.     

Synthesis and structural chemistry of alkali metal tris(HMDS) magnesiates containing chiral diamine donor ligands

Six alkali metal tris(HMDS) magnesiate complexes (HMDS, 1,1,1,3,3,3,-hexamethyldisilazide) containing chiral diamine ligands have been prepared and characterised in both the solid- and solution-state. Four of the complexes have a solvent-separated ion pair composition of the form [{M·(chiral diamine)(2)}(+){Mg(HMDS)(3)}(-)] [M = Li for 1 and 3, Na for 2 and 4; chiral diamine = (-)-sparteine for 1 and 2, (R,R)-TMCDA for 3 and 4, (where (R,R)-TMCDA is N,N,N',N'-(1R,2R)-tetramethylcyclohexane-1,2-diamine)] and two have a contacted ion pair composition of the form [{K·chiral diamine}(+){Mg(HMDS)(3)}(-)](n) [chiral diamine = (-)-sparteine for 5 and (R,R)-TMCDA for 6]. In the solid-state, complexes 1-4 are essentially isostructural, with the lithium or sodium cation sequestered by the respective chiral diamine and the previously reported anion consisting of three HMDS ligands coordinated to a magnesium centre. As such, complexes 1-4 are the first structurally characterised complexes in which the alkali metal is sequestered by two molecules of either of the chiral diamines (-)-sparteine (1 and 2) or (R,R)-TMCDA (3 and 4). In addition, complex 4 is a rare (R,R)-TMCDA adduct of sodium. In the solid state, complexes 5 and 6 exist as polymeric arrays of dimeric [{K·chiral diamine}(+){Mg(HMDS)(3)}(-)](2) subunits, with 5 adopting a two-dimensional net arrangement and 6 a linear arrangement. As such, complexes 5 and 6 appear to be the only structurally characterised complexes in which the chiral diamines (-)-sparteine (5) or (R,R)-TMCDA (6) have been incorporated within a polymeric framework. In addition, prior to this work, no (-)-sparteine or (R,R)-TMCDA adducts of potassium had been reported.     

Asymmetric intramolecular [2 + 2] photocycloadditions: alpha- and beta-hydroxy acids as chiral tether groups

Chiral alpha- and beta-hydroxy acids such as (S)-lactic acid, (S)-phenyllactic acid, (S)-mandelic acid, or (3R)-3-hydroxybutyric acid have been used as tether groups for intramolecular and diastereoselective [2 + 2] photocycloaddition of 3-oxocyclohexene carboxylic acid derivatives. Total regiocontrol toward the straight adduct and high diastereoselectivities (up to 94%) were observed in the case of butenyl lactate 11. After separation of the two diastereoisomers, cleavage of the chiral tether under basic conditions afforded cyclobutane lactones in good yield and enantiomeric pure form. An X-ray structure has been recorded that confirmed the relative and absolute configuration of the three contiguous stereogenic centers assigned according to CD spectra.     

Asymmetric Samarium-Reformatsky Reaction of Chiral alpha-Bromoacetyl-2-oxazolidinones with Aldehydes

The samarium(II) iodide mediated asymmetric Reformatsky-type reaction of chiral 3-bromoacetyl-2-oxazolidinones with various aldehydes was studied. A series of chiral 4-substituted 2-oxazolidinones 1-3 and 5,5-disubstituted "SuperQuat" oxazolidinones 4-5 were employed as chiral auxiliaries of the alpha-bromoacetic acid. The reaction of 1 with various aldehydes gave the alpha-unbranched beta-hydroxy carboximides in good yields with high diastereomeric excess values (up to >99% de). The majority of the reaction product derived from 5,5-diphenyl SuperQuat 5 were highly crystallinity; a single recrystallization yielding a diastereomerically pure product with the other diastereomer not detectable by spectroscopic methods. The absolute configurations of the beta-hydroxy carboximides were determined by signs of optical rotations of the corresponding known ethyl esters referring to the literature values. Hydrolytic cleavage of the appended of beta-hydroxy moieties from the auxiliary SuperQuats was readily achieved under mild conditions using lithium hydroxide; the corresponding carboxylic acids and the returned SuperQuats were obtained in good yields without any evidence of racemization. The first step of the reaction is the reduction of the alpha-bromo group to produce the samarium enolate, which adds to an aldehyde. The absolute configuration of the adduct (7i) derive from benzaldehyde was found to be R, with the samarium enolate favoring the transition state predicted from chelation control of the reagent; this is in analogy to the discussion that has been used for the corresponding titanium enolate. The stereochemistry of the reaction may be explained by incorporating the Nerz-Stormes-Thornton chair transition structure model.     

Solvent-dependent mixed complex formation-NMR studies and asymmetric addition reactions of lithioacetonitrile to benzaldehyde mediated by chiral lithium amides

Lithioacetonitrile and a chiral lithium amide with an internally coordinating methoxy group form mixed dimers in diethyl ether (DEE) and in tetrahydrofuran (THF) according to NMR studies. Based on the observed (6)Li,(1)H heteronuclear Overhauser effects, in THF lithioacetonitrile is present in a mixed complex with the chiral lithium amide, and this complex has a central N-Li-N-Li core. In DEE, on the other hand, the acetonitrile anion bridges two lithiums of the dimer to form a central six-membered Li-N-C-C-Li-N ring. Gauge individual atomic orbital DFT calculations of the (13)C NMR chemical shifts of the DEE- and THF-solvated mixed dimers show good agreement with those obtained experimentally. Lithioacetonitrile complexed to the chiral lithium amide has been employed in asymmetric addition to benzaldehyde in both DEE and THF. In THF the product, (S)-3-phenyl-3-hydroxy propionitrile, is formed in 55 % ee and in DEE the R enantiomer is formed in 45 % ee. This change in stereoselectivity between solutions in DEE and THF was found to be general among a number of different chiral lithium amides, all with an internal chelating methoxy group.     

Mechanistic insight into stereoselective carbolithiation

This article addresses the mechanistic features of asymmetric carbolithiation of β‐methylstyrenes. While often the presence of functional groups is required to obtain high enantioselectivities in carbolithiation reactions, simple β‐methylstyrene also gives high selectivities in (?)‐sparteine‐mediated addition of alkyl lithium compounds. Computational studies on the carbolithiation of β‐methylstyrene with (?)‐sparteine show that the observed selectivities are the result of repulsion effects in the diastereomeric transition states between the (?)‐sparteine ? alkyl lithium adduct and the β‐methylstyrene, upon approximation of the two reactants. In contrast, for the ortho‐amino β‐methylstyrene (E)‐benzyl(2‐propenylphenyl)amine ( 4 ) X‐ray structure analyses of intermediate lithium amides indicate a carbolithiation mechanism in which one side of the double bond is shielded by the amide moiety, leaving only one side free for approach of the chiral alkyl lithium adduct.     

Synthesis, X-ray and neutron diffraction characterization, and ionic conduction properties of a new oxothiomolybdate Li3[Mo8S8O8(OH)8[HWO5(H2O)]] x 18H2O

The new oxothiomolybdate anion [Mo8S8O8(OH)8[HWO5(H2O)]]3- (denoted HMo8W3-) has been synthesized in aqueous solution by an acido-basic condensation reaction. Four (Mo(V)2S2O2) building blocks are connected through hydroxo bridges around a central [W(VI)O6] octahedron. X-ray and neutron diffraction studies have been performed on single crystals of the lithium salt Li3[Mo8S8O8(OH)8[HWO5(H2O)]] x 18H2O (Li3HMo8W x 18H2O) in an aqueous grown from HMo8W3- solution of LiCl (1 M). The neutron diffraction experiment enabled us to locate both the protons and the lithium ions. In the structure of Li3HMo8W x 18H20, ring-shaped anions interleaved by a cluster of disordered hydrogen-bonded water molecules stack on top of each other along lithium pillars. The lithium columns are formed by alternating edge-sharing octahedra and tetrahedra, with one lithium site in four being totally vacant. Ionic conductivity measurements on pressed pellets have shown that Li3HMo8W x 18H2O is a good ionic conductor at room temperature (sigma = 10(-5) S cm(-1)), but the ionic conductivity on single crystals is smaller by two orders of magnitude and is isotropic; this suggests the main path of conduction involves surface protons rather than lithium ions of the bulk.     

Asymmetric Reduction Using Lithium Aluminum Hydride Modified with Chiral Ligand Prepared from (1R)-(-)-Myrtenol

The reduction of prochiral ketones with a chiral reducing reagent, prepared from lithium aluminum hydride and (1R,2S,3S,5R)-(-)-10-methoxypinanediol (2), produced secondary chiral alcohols in good chemical yields (57–98%) and moderate enantiomeric excess (8–72%).     

Enantiospecific syntheses of copper cubanes, double-stranded copper/palladium helicates, and a (dilithium)-dinickel coronate from enantiomerically pure bis-1,3-diketones--solid-state self-organization towards wirelike copper/palladium strands

Enantiomerically pure, vicinal diols 1 afforded in a two-step synthesis (etherification and subsequent Claisen condensation) chiral bis-1,3-diketones H(2)L((S,S)) (3 a-c) with different substitution patterns. Reaction of these C(2)-symmetric ligands with various transition-metal acetates in the presence of alkali ions generated distinct polynuclear aggregates 4-8 by diastereoselective self-assembly. Starting from copper(II) acetate monohydrate and depending on the ratio of transition-metal ion to alkali ion to ligand, chiral tetranuclear copper(II) cubanes (C,C,C,C)-[Cu(4)(L((S,S)))(2)(OMe)(4)] (4 a-c) or dinuclear copper(II) helicates (P)-[Cu(2)(L((S,S)))(2)] (5) could be synthesized with square-pyramidal and square-planar coordination geometry at the metal center. In analogy to the last case, with palladium(II) acetate double-stranded helical systems (P)-[Pd(2)(L((S,S)))(2)] (6,7) were accessible exhibiting a linear self-organization of ligand-isolated palladium filaments in the solid state with short inter- and intramolecular metal distances. Finally, the introduction of hexacoordinate nickel(II) in combination with lithium hydroxide monohydrate and chiral ligand H(2)L((S,S)) (3 a) allowed the isolation of enantiomerically pure dinuclear nickel(II) coronate [(LiMeOH)(2) subset{(Delta,Lambda)-Ni(2)(L((S,S)))(2)(OMe)(2)}] (8) with two lithium ions in the voids, defined by the oxygen donors in the ligand backbone. The high diastereoselectivity, induced by the chiral ligands, during the self-assembly process in the systems 4-8 could be exemplarily proven by circular dichroism spectroscopy for the synthesized enantiomers of the chiral copper(II) cubane 4 a and palladium(II) helicate 6.     

Structure of molybdenum and tungsten sulfide M(x)S(y)+ clusters: experiment and DFT calculations

A combination of experiment and density functional theory was used to investigate the energetics of CO adsorption onto several small M(x)S(y)(+) (M = Mo, W; x/y = 2/6, 3/7, 5/7, 6/8) clusters as a probe of their atomic and electronic structure. Experimentally, tandem mass spectrometry was used to measure the relative yields of M(x)S(y)(+)(CO)(n) cluster adducts formed by collisions between a beam of mass-selected M(x)S(y)(+) cluster ions and CO molecules in a high-pressure collision cell (hexapole ion guide). The most probable M(x)S(y)(+)(CO)(n) adducts observed are those with n < or = x, that is, only one CO molecule bound to each metal site. The notable exception is the M(5)S(7)(+) cluster, for which the n = 6 adduct is found to have nearly the same intensity as the n = x = 5 adduct. Density functional calculations were used to search for the lowest energy structures of the bare M(x)S(y)(+) clusters and to obtain their relative stability for sequential CO binding. The calculated trends in CO binding energies were then compared to the experimental adduct distributions for assigning the ground-state structures. In this way, it was possible to distinguish between two nearly isoenergetic ground-state isomers for the M(2)S(6)(+) and M(3)S(7)(+) clusters, as only one isomer gave a calculated CO stabilization energy trend that was consistent with the experimental data. Similar comparisons of predicted and observed CO adsorption trends also provide evidence for assigning the ground-state structures of the M(5)S(7)(+) and M(6)S(8)(+) clusters. The latter contain metallic cores with most of the sulfur atoms bonded along the edges or in the faces of the metal core structure. The n = 6 and 7 adducts of M(5)S(7)(+) are predicted to be more stable than the n = x = 5 adduct, but only the n = 6 adduct is observed experimentally. The DFT calculations show that the n = 7 adduct undergoes internal bond breaking whereas the n = 6 framework is stable, albeit highly distorted. For the M(6)S(8)(+) cluster, the calculations predict that the two lowest energy isomers can bind more than six CO molecules without fragmentation; however, the apparent binding energy drops significantly for adducts with n > 6. In general, the ability of these small M(x)S(y)(+) clusters to bind more CO molecules than the number of metal atoms is a balance between the gain in CO adsorption energy versus the strain introduced into the cluster structure caused by CO crowding, the consequences of which can be fragmentation of the M(x)S(y)(+)(CO)(n) cluster adduct (n > x).     

Asymmetric synthesis of (-)-adaline

[reaction: see text] An enantioselective total synthesis of (-)-adaline has been achieved starting from a chiral 6,6-disubstituted piperidone derivative previously prepared by diastereoselective allylation of a chiral tricyclic N-acyl-N,O-acetal. The key steps include lithium ion-activated SN2-type alkynylation of the tricyclic N,O-acetal leading to exclusive formation of the (6S)-ethynylpiperidine and ring-closing olefin metathesis of the (2R,6S)-cis-2,6-dialkenylpiperidine for constructing the bridged azabicyclononane.     

Heterometal expansion of oxozirconium carboxylate clusters

Although representing a 'thermodynamic sink', the octahedral oxozirconium {Zr(6)O(4)(OH)(4)} cluster structure can be magnetically functionalized by up to six 3d metal cations with a combination of flexible aminoalkoxide and carboxylate ligands.     

Trigonal bipyramidal platinum complexes as models for ziegler-nasa catalytic sites

Five-coordinated η²-adducts of (+)-(S)-3-methyl-1-pentene (SMP) and (R,S)-3-methyl-1-pentene (RSMP) of the type [PtCl₂(η²-olefin)(α-di-hydrazone)] were prepared. In solution the more stable adducts are those which have the olefin presenting to Pt the face of opposite configuration to that of the chiral substituent. In the solid state the same situation is found by X-ray analysis for the adduct of SMP, while ¹H NMR studies point to the conclusion that the same configuration as the chiral substituent is preferred in the solid adduct of RSMP. These observations are compared with those in previous reports on coordination of SMP on square planar Pt and stereoselective polymerization.     

(S,S)N,N'-双(对氯-α-异丙基苄基)-1,10-二氮杂-18-冠-6的合成及其应用

手性冠醚被用作不对称合成的手性试剂,或者成为具有构型识别能力的主体,它们已成为冠醚化学中的一个引人注目的领域。近年来,也有一些关于含氮手性冠醚的报道,但大多数以氨基酸为基本原料。作者应