Asymmetric azo-ene reactions using the chiral azo-enophile di-(−)-(1R,2S)-2-phenyl-1-cyclohexyl diazenedicarboxylate

The preparation of di-(−)-(1R,2S)-2-phenyl-1-cyclohexyl diazenedicarboxylate 4 is described. Reaction of (1R,2S)-2-phenyl-1-cyclohexanol 1 with excess phosgene in the presence of quinoline afforded chloroformate 2 which was treated directly with hydrazine monohydrate (0.5 equiv.) to afford di-(−)-(1R,2S)-2-phenyl-1-cyclohexyl diazanedicarboxylate 3. Oxidization of 3 to the azo-enophile 4 was then readily effected in high yield using N-bromosuccinimide and pyridine. The azo-ene reactions of 4 with the alkenes cyclohexene 5, cyclopentene 6, trans-3-hexene 7 and trans-4-octene 8 were carried out using the Lewis acid tin(IV) chloride. Use of cyclohexene 5 afforded the ene adduct 9 in 80% yield with a diastereomeric excess of >97:3 whilst the use of cyclopentene 6, trans-3-hexene 7 and trans-4-octene 8 afforded the ene adducts 10 (77%), 11 (71%) and 12 (92%) with a diastereomeric excess of 86:14 in each case. Use of the conjugated aromatic acyclic alkene 13 afforded the product of an ionic addition, namely, chloride 14 in 57% yield. Cleavage of the N–N bond of the ene adduct 9 was effected using lithium in liquid ammonia affording the carbamate 16 in moderate yield.     

Asymmetric synthesis of (S)- and (R)-α-methylserine based on the chiral recyclable reagent (S)-N-(2-benzoyl-phenyl)-1-benzylpyrrolidine-2-carboxamide

Both enantiomers of -methylserine were synthesized with the use of Ni^II complexes based on the chiral recyclable reagent (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide. Intermediate diastereomeric complexes were separated by crystallization of their O-acetyl derivatives.     

Halo-substituted (S)-N-(2-benzoylphenyl)-1-benzylpyrolidine-2-carboxamides as new chiral auxiliaries for the asymmetric synthesis of (S)-α-amino acids

The synthesis of new chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide (1a), (S)-N-(2-benzoylphenyl)-1-(pentafluorobenzyl)pyrrolidine-2-carboxamide (1b), and (S)-N-(2-benzoylphenyl)-1-(4-isopropoxytetrafluorobenzyl)pyrrolidine-2-carboxamide (1c) and their application in the asymmetric synthesis of amino acids using Ni^II complexes of their Schiff"s bases with alanine and glycine are described. Compound 1a is particularly appropriate for highly stereoselective synthesis of -methyl--amino acids with high enatiomeric purity (ee >95%).     

Synthesis,properties, and reactions of enantiomerically pure,chiral fluorous phosphines of the formula (menthyl)P(CH2CH2(CF2)n−1CF3)2 (n=6, 8)

Reactions of (menthyl)PH₂ and H₂CCHR_f6 (menthyl=1R,3R,4S; R_fn=(CF₂)_n−1CF₃) or H₂CCHR_f8 (AIBN, refluxing THF) give (menthyl)PH(CH₂CH₂R_fn) and then (menthyl)P(CH₂CH₂R_fn)₂ (n=6, 7; n=8, 8), but with purification or other difficulties at each stage. Reactions of (menthyl)PCl₂ with IMgCH₂CH₂R_fn give, under careful conditions, analytically pure 7 or 8 in 28–32% yields after distillation. Some R_fn(CH₂)₄R_fn also form. These represent the first chiral (and non-racemic) fluorous phosphines. Reactions of 7 or 8 with [Ir(COD)Cl]₂ and CO give trans-[(menthyl)P(CH₂CH₂R_fn)₂]₂Ir(Cl)(CO) (n=6, 71%; 8, 51%) as analytically pure yellow oils. Their IR ν_CO values show the donor/acceptor properties of 7 and 8 to be intermediate between those of P((CH₂)₃R_f8)₃ and P((CH₂)₄R_f8)₃. The CF₃C₆F₁₁:toluene partition coefficients of 7 and 8 (27°C, 78.4:21.6 and 93.7:6.3) are distinctly lower than those of P((CH₂)₂R_fn)₃ (n=6, 98.8:1.2; n=8, >99.7:<0.3), reflecting the replacement of a linear C₈–C₁₀ group that is ca. 75–80% fluorinated by a cyclic C₁₀ terpenyl group. Reactions of 7 or 8 with [Rh(COD)Cl]₂ give [(menthyl)P(CH₂CH₂R_fn)₂]Rh(Cl)(COD) (n=6, 69%; 8, 70%) as orange crystallizable oils.     

Group VIII transition metal complexes with the chiral diphosphazane ligand (S)-α-(Ph2P)2N(CHMePh): Synthesis and structural characterization

The chiral ligand S-(Ph₂P)₂N(CHMePh) reacts with Ni(CO)₄ in benzene solution to yield the mononuclear complex [Ni(CO)₂{κ²-(PPh₂)₂N(CHMePh)}] (1). The reactions of the chiral ligand with the solvated complexes [(η⁵-C₅Me₅)MCl(solvent)₂]BF₄ (M = Rh, Ir) or with the binuclear complex [{(η⁶-C₆Me₆)RuCl}₂(μ-Cl)] in the presence of a chloride scavenger, give cationic complexes of the type [(ηⁿ-ring)MCl{κ²-(PPh₂)₂N(CHMePh)}]BF₄ [ηⁿ-ring = η⁵-C₅Me₅; M = Rh (2), Ir (3). η⁶-C₆Me₆; M = Ru (4)]. The ³¹P NMR spectra of compounds 2-4 show two signals corresponding of two phosphorus nuclei with different chemical environments. The related complex [(η⁵-C₅H₅)Fe(CO){κ²-(PPh₂)₂N(CHMePh)}]BF₄ (5) was prepared by reaction of the ligand with the complex [(η⁵-C₅H₅)Fe(CO)₂I] in toluene following by a metathesis with AgBF₄. This compound exhibits only one signal in the ³¹P NMR spectra at room temperature, which splits into two signals at low temperature (213 K). The crystal structures of complexes 2, 3 and 5 have been determined by X-ray diffraction studies. All complexes show the presence of an intramolecular π-stacking interaction. The separation between least-squares planes defined by the two intramolecularly stacked phenyl rings are in the range 3.318-3.649 Å.     

Synthesis of binuclear complexes of PdCl2 with chiral α,α′-diamino-meta-xylene dioximes H2L1, H2L2, and H2L3, the derivatives of the terpenes (+)-3-carene, (R)-(+)-limonene, and (S)-(−)-α-pinene. Crystal structure of [Pd2(H2L1)Cl4]

Chiral α,α′-diamino-meta-xylene dioximes H₂L¹, H₂L², and H₂L³ were obtained from the naturally occurring terpenoids (+)-3-carene, (R)-(+)-limonene, and (S)-(?)-α-pinene, respectively. Reactions of these ligands with PdCl₂ gave the diamagnetic complexes Pd₂(H₂L¹)Cl₄ (I), Pd₂(H₂L²)Cl₄ (II), and Pd₂(H₂L³)Cl₄ (III). According to X-ray diffraction data, the crystal structure of complex I consists of acentric binuclear molecules [Pd₂(H₂L¹)Cl₄]. The coordination polyhedron PdN₂Cl₂ is a square distorted in a tetrahedral manner (trapezium) made up of two N atoms of the tetradentate bridging cyclic ligand H₂L¹ and two Cl atoms. The fragments PdCl₂ in the complex are cis to each other. According to the ¹H NMR spectra of complexes I–III in CDCl₃, the organic ligands are coordinated through the N atoms; in solution, the complexes exist in several forms.     

DiastereoselectiveandEnantioselectiveSynthesisof(1S,2S)-2-Ethyl-1-aminocyclopropaneCarboxylicAcid

During the last decade, 1-aminocyclopropanecarboxylic acid and its derivatives (ACCS) have attracted increasing attention of organic and bioorganic chemists due to their outstanding biological properties, ranging from antimicrobial, insecticidal, plant growth and fruit ripening controls, etc.1. Moreover, the three-membered carbocycle provides building blocks of unprecedented synthetic potential because it undergoes selective ring opening, ring enlargement or cycloaddition reactions2. The mo…     

( S )-(?)-α-Methylbenzylamine as chiral auxiliary in the synthesis of (+)-lortalamine

Abstract  

(+)-Lortalamine was synthesised using (S)-(−)-α-methylbenzylamine as a chiral auxiliary. The stereochemistry of an intermediate compound was established on the basis of X-ray crystallography, allowing unambiguous assignment of the absolute configuration.     

Diastereoselective LiAlH4 reduction of chiral ketone hydrazones derived from (R)-(–)-2-aminobutan-1-ol

Various chiral N,N-dialkylhydrazines were prepared in four to five steps from (R)-(–)-2-aminobutan-1-ol 6. They reacted with various prochiral ketones, thus giving the corresponding hydrazones. Reduction of the latter by means of LiAlH₄ afforded N,N,N′-trisubstituted hydrazines whose d.e.s were in the range 43–100%. Interestingly, LiAlH₄ reduction of the four N-trifluoroethylhydrazones 34 and 38–40 yielded the hydrazines 46 and 48–50, respectively, and with d.e.s=100% by ¹H and ¹³C NMR.     

An improved synthesis of (-)-7-isopropyl-cis-l-amino-2-indanol the chiral auxiliary for 6π-azaelectrocyclization

(-)-7-Isopropyl-cis-1-amino-2-indanol,a key chiral auxiliary and ligand in the highly stereo-selective asymmetric 6π-azaelectrocyclization, has been prepared previously by two methods.Each however involved using of one extreme condition, i.e.high temperature or high pressure,for the respective reaction.A modified reaction route employed mild condition for synthesis was presented in this report.     

Synthesis of (-)-swainsonine and (-)-8-epi-swainsonine by the addition of allenylmetals to chiral α,β-alkoxy sulfinylimines

The asymmetric synthesis of (-)-swainsonine and (-)-8-epi-swainsonine is reported through the addition of either the allenylzinc or the allenyl lithio cyanocuprate reagents derived from [3-(methoxymethoxy)prop-1-ynyl]trimethylsilane to enantiopure α,β-dialkoxy N-tert-butanesulfinylimines derived from d-erythronolactone.     

First synthesis of (−)-(1R,4R)- and (+)-(1S,4S)-(7,7-dimethyl-2-methylene-bicyclo[2.2.1]hept-1-yl)-methanol: new fenchone-derived chiral auxiliaries

The treatment of (+)- or (−)-fenchones epoxides with 1:2 85% H₃PO₄:DMSO for 30 min at 20°C induced an enantiospecific Wagner–Meerwein rearrangement affording new C(10)-O-substituted camphor derivatives which could prove useful as chiral auxiliaries.     

Diastereoselective hydrogenation of α,β-unsaturated but-2-enamides to access the chiral 3-(p-tolyl) butanoic acids

An alternative methodology for the synthesis of chiral 3-(p-tolyl) butanoic acids is presented. This was accomplished through the diastereoselective hydrogenation reaction of different chiral N-3-(p-tolyl) but-2-enamides, using Pd/C in EtOH, to produce the corresponding chiral N-3-(p-tolyl) butanamides with high chemical yields and moderate diastereomeric ratios. Removal of the chiral auxiliary from N-3-(p-tolyl) butanamides gave the respective enantiomerically pure acids.     

Synthesis of chiral 2-(2′-pyrrolidinyl)pyridines from (S)- and (R)-proline: potential ligands of the neuronal nicotinic acetylcholine receptors

A new strategy for a straightforward synthesis of novel optically active nicotine analogues starting from (S)- and (R)-proline is reported utilizing as the key steps the inverse electron demand Diels–Alder reaction of, hitherto unknown, chiral 5-(2′-pyrrolidinyl)-1,2,4-triazines (S)- and (R)-16. These serve as appropriate precursors for the preparation of different, highly enantiomerically enriched 2-(2′-pyrrolidinyl)pyridines, modifications of natural (−)-nornicotine and (−)-nicotine and potential ligands of the neuronal nicotinic acetylcholine receptors. The multistep syntheses proceed under mild conditions, with good overall yields and with stereochemical integrity of the original stereogenic centers.     

Synthesis of propyl O-(α-L-rhamnopyranosyl)-(1→3)-[2,4-di-O-(2s-methylbutyryl)-α-L-rhamno-pyranosyl]-(1→2)-(3-O-acetyl-β-D-glucopyranosyl)-(1→2)-β-D-fucopyranoside,the tetrasaccharide moiety of Tricolorin A

Propyl O-(α-L-rhamncpyranosyl)-(1→3)-[2,4-di-O-(2s-methylbutyryl)-α-L-rham-nopyranosyl]-(1→2)-(3-O-acetyl-β-D-glucopyranosyl)-(1→2)-β-D-fucopyranoside (1), the tetrasac-charide moiety of Tricolorin A, was synthesized in total 23 steps with a longest linear sequence of 10 steps, and overall yield of 3.7% from D-Glucose. The isomerization of the dioxolane-type berzyli-dene in the presence of NIS/AgOTf was observed. Tetrasaccharide 1 exhibited no activity against the cultured P388 cell as Tricolorin A did.     

Synthesis and Crystal Structure of (2S,2'S,4'R)-2-(1-Hydroxy-1-ethylpropyl)-1-[(1'-p-tosyl-4'-hydroxypyrrolidin-2'-yl)methyl]pyrrolidine

1 INTRODUCTION In recent years, chiral β-amino alcohols have attracted much attention due to their special bio- logical functions and catalytic activities. Chiral β- amino alcohol moieties are usually found not only in natural products (e.g., cinchona alkaloids, ephe- drine, toxal, etc.) with special biological activities[1, 2], but also critical structural segments of some syn- thesized biologically active compounds, such as adrenergic agonists or antagolist[3, 4] and inhibitors for HI…     

Synthesis,Structure and Biological Activities of 2-(1H- 1,2,3-Benzotriazol-1-yl)-1-(4-methylphenyl)-2- (1H-1,2,4-triazol-1-yl)-1-ethanone

IntroductionTriazole derivatives have become the most rapidlyexpanding group of antifungal compounds with advanta-ges of lowtoxicity, high oral bioavailability and broad-spectrum antifungal activity, which can be used againstfungi including most yeasts an…     

Electrochemical and electrocatalytic studies of the N,N′-(1R,2R)-(–)-1,2-cyclohexylenebis(salicylideneiminato)cobalt(II) complex

The electrochemical properties and catalytic activity of a Co(II) complex with the optically active Schiff base derived from (1R,2R)-(–)-cyclohexanediamine and salicylaldehyde have been studied in non-aqueous solutions. When dissolved in deoxygenated non-aqueous solutions, the complex exhibits reversible redox properties for the Co(II)/Co(III) couple. Electrochemical reduction of oxygen and oxidation of cobalt(II) was observed on cyclic voltammograms of solutions containing both dioxygen and the Schiff base-cobalt(II) complex. An anodically formed film on a platinum electrode, studied by means of X-ray photoelectron spectroscopy, revealed the presence of the oxidized Co(III) species. Cyclic voltammetry of oxygenated solutions examined after a period of time indicates an electrochemical activity of coordinated superoxo/peroxo species in the 0.7–1.1 V potential range. In the presence of 4-methyl-1-cyclohexene the cyclic voltammetry curves reveal changes similar to those caused by the removal of oxygen. The GC-MS technique was used to identify some of the products formed by the catalytic oxidation of cyclohexene and 4-methyl-1-cyclohexene. Electronic Publication     

Syntheses,characterizations, crystal structures,and in vitro antitumor activities of chiral triorganotin(IV) complexes containing (S)-(+)-2-(4-isobutyl-phenyl)propionic and (R)-(+)-2-(4-hydroxyphenoxy)propionic acid ligands

Four new chiral triorganotin(IV) carboxylates, [(R₃Sn)(O₂C₁₃H₁₇)] _n (R?=?Me 1, Ph 2), [(R₃Sn)(O₂C₁₃H₁₇)] (R?=?n-Bu 3), and [(R₃Sn)(O₄C₉H₉)] _n (R?=?Me 4), have been synthesized by reaction of (S)-(+)-2-(4-isobutyl-phenyl)propionic acid and (R)-(+)-2-(4hydroxyphenoxy)propionic acid with triorganotin(IV) chloride in the presence of sodium ethoxide. The complexes have been characterized by elemental analyses, FT-IR, NMR (¹H, ¹³C, and ¹¹⁹Sn) spectra, and X-ray crystallography diffraction analyses. Structural analyses show that 1 has a 1-D infinite chiral zigzag chain structure. Complexes 2 and 4 have a 1-D spring-like chiral helical chain with a channel, while 3 is a monomer. Antitumor activities of 1–4 have been studied.     

微波辐射下合成5-(2-甲基/三氟甲基-苯并咪唑-1-亚甲基)-3-(苯基/p-取代苯基)-2H-1',2',4'-三唑[3,4-b]-1

分别采用微波辐射法和加热回流的常规方法, 将1-氨基-2-(2-甲基/三氟甲基-苯并咪唑-1-亚甲基)-5-巯基-1,3,4-三唑与α-溴代芳基乙酮3a～3e反应, 合成了一系列未见文献报道的1,2,4-三唑[3,4-b]-1',3',4'-噻二嗪类化合物4a～4e 和5a～5e. 微波辐射法具有反应时间短、产率高、副反应少等优点. 标题化合物经元素分析, IR, ¹H NMR, MS确证结构.