Chlorotrimethylsilane promoted asymmetric Michael reaction of chiral enamines of α-alkyl β-keto esters

By the promotion of chlorotrimethylsilane, asymmetric Michael reaction of the chiral enamines (2) of α-alkyl β-keto esters (1) with methyl vinyl ketone and ethyl acrylate proceeded to afford, after hydrolysis, either enantiomer of the corresponding adducts (4) in a good enantioselectivity.     

Functionalized enamines—XXXII : Reaction of β-amino-α, β-unsaturated esters and amides with benzyl and cinnamyl bromides

Reactions of β-aminoacrylic esters (1–c) and amides (1d–o) with benzyl bromide 2 and cinnamyl bromide 3 give products which are dependent both upon the nature of the amine component of the enamine and, in the case of the amides, upon the amine from which the amide is derived. The β-enamino esters react with benzyl bromide to yield predominantly dialkylated products in the case of the pyrrolidine ester 1a. Reactions of the same esters with cinnamyl bromide yield mixtures of cinnamyl and 2-phenylpropenyl-substituted formylacetic esters. The enamino amides 1d–f react to yield the expected alkylated derivatives. The anilides 1i–o exhibit nucleophilic reactivity at the aniline nitrogen. A mechanism leading to the observed products is proposed.     

Regioselective SN′ allylic substitution versus 1,4-addition: Synthesis of α-substituted β,γ-unsaturated esters

The reaction of the higher order organocuprate reagents R₂Cu(CN)Li₂-BF₃ with γ-bromo α,β-unsaturated esters gives with very high selectivity α-substituted β,γ-unsaturated esters arising from a SN′ allylic substitution. This reaction allows an easy access to α-silyl β,γ-unsaturated esters.     

Synthese stereoselective d'esters α,β- ethyleniques α-methyles Z ou E par la reaction de wittig-horner a partir de phosphonates ou d'oxydes de phosphine

The reaction of α-branched aldehydes with diethyl 1-carbomethoxyethyl phosphonate 1b in THF/nBuLi at low temperature leads stereoselectively to Z α-methyl α,β-unsaturated esters. From a linear aldehyde, the reaction is less stereoselective, while from α,β-unsaturated ones, the E isomers are predominantly formed in good yields. From diphenyl 1-carbomethoxyethyl phosphine oxide 2b, E α-methyl α,β-unsaturated esters are stereoselectively formed either in DMF/tBuOK or in phase transfer conditions, whatever the starting aldehyde is, also in good yields. This reagent can thus advantageously replace the corresponding P-ylid. In all cases, the reaction conditions are determined so that by-products formation is minimized.     

Additive Pummerer reactions of vinylic sulfoxides. Synthesis of γ-hydroxy-α,β-unsaturated esters, α-hydroxyketones, and 2-phenylsulfenyl aldehydes and primary alcohols

Treatment of β-monosubstituted vinylic sulfoxides 1 with trifluoroacetic anhydride in dichloromethane gave excellent yields of 1,2-bis(trifluoroacetoxy)thioethers 6. Mildly basic methanolysis of 2-alkyl-substituted 6 gave α-hydroxyaldehydes 11 as monomer-dimer mixtures; similar treatment of the 2-aryl analogues afforded aryl (hydroxymethyl) ketones 12. Compounds 11 underwent Wittig reactions with methoxycarbonylmethylenetriphenylphosphorane to give high yields of γ-hydroxy-α,β-unsaturated esters 13, predominantly as the E-isomers. β-Monosubstituted vinylic sulfoxides 1 possessing a β-aryl group, and β-disubstituted vinylic sulfoxides 3 reacted with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride to give 2-(phenylsulfenyl)acylals 14. These gave 2-phenylsulfenyl aldehydes 15 upon basic methanolysis, and the corresponding primary alcohols 16 on reduction with sodium borohydride. Reaction of both geometric isomers of enantiomerically pure vinylic sulfoxide 1o with TFAA gave racemic 6o as a mixture of diastereomers. Reaction of optically pure (E)- and (Z)-1p with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride gave acylal 19 in 10.5 and 23% e.e., respectively.     

Lewis acid promoted aldol additions of α-thiosilylketeneacetals to α-alkoxy aldehydes: diastereoselective synthesis of -α-methylene-β-hydroxy-∂-alkoxy esters.

MgBr₂ mediated addition of Methyl α-methylthio propionate silylketene acetal to α and α,β-alkoxy aldehydes is highly 3,4 -selective (18:1). -α- methylene-β- hydroxy-∂-alkoxy esters (6) and (8) are synthesized.     

The first example of α-organoseleno arsonium ylides and its Wittig-type reaction

α-Organoseleno arsonium ylide 3 was synthesized for the first time by a phenylselenenylation-transylidation reaction. It has sufficient activity to carry out the Wittig-type reaction, affording a novel method for the stereoselective synthesis of (Z)-α-phenyl-seleno-α, β-unsaturated esters 6.     

Syntheses of methyl α-dl-mycaminoside, methyl α-dl-oleandroside, methyl β-dl-cymaroside, methyl α-dl-tyveloside and methyl α-dl-chromoside C

Five rare hexoses, which are components of antibiotics or cardiac glycosides, have been synthesized as methyl glycosides through a common intermediate methyl 2,3-dehydro-2,3,6-trideoxy-α-dl glucopyranoside (7). Epoxidation and subsequent treatment with dimethylamine of7 afforded methyl α-dl-mycaminoside (9). The addition reaction of MeOH to12 gave methyl α-dl-oleandroside (15) and methyl β-dl-cymaroside (17). The hydroxymercuration and subsequent reduction of12 afforded methyl α-dl-chromoside C (19) and methyl β-dl-tyveloside (25).     

A simple method to prepare single isomer tetrasubstituted olefins by successive Suzuki–Miyaura cross-couplings of E-β-chloro-α-iodo-α,β-unsaturated esters

A convenient method of synthesizing tetrasubstituted olefins as single isomers is described. E-β-Chloro-α-iodo-α,β-unsaturated esters are first converted into the corresponding E-β-chloro-α,β-unsaturated esters using Suzuki–Miyaura coupling reactions with arylboronic acids and alkenylboronic acids. These transformations gave complete selectivity, and proceeded with substitution at the more activated α-iodide position. These compounds, isolated as single isomers, were then transformed into tetrasubstituted olefins by Suzuki–Miyaura couplings with arylboronic acids, alkenylboronic acids, and alkyl boranes to afford the corresponding tetrasubstituted olefins as single isomers. During this coupling process, it was discovered that the use of small ligands, such as PMe₃ or PEt₃, was critical for efficient coupling. The stereochemistry and regiochemistry of the products were unequivocally established using NMR methods.     

Preparation of α- or β-trifluoromethylated vinylstannanes and their cross-coupling reactions

α- or β-Trifluoromethylated vinylstannanes 1, 2a, 3 and 4 were prepared form 1,1-bis(phenylthio)-2,2,3,3,3-pentafluoropropylbenzene (5) via several steps. The cross-coupling arylation reactions of 1–4 with aryl iodides bearing a bromo, methoxy, methyl, nitro or trifluoromethyl group on para- or meta-position of benzene ring afforded the corresponding coupling products in good yields. Compounds 1, 2a and 4 underwent the acylation reaction with various types of acyl chlorides to give the corresponding trifluoromethylated enone derivatives in good yields. Reduction of trifluoromethylated enone derivatives with LiAlH₄, followed by Fridel-Craft’s type of cyclization with AlCl₃ provided trifluoromethylated indene derivatives in good yields.     

Biosynthesis of aristeromycln: Evidence for the intermediacy of a 4β-hydroxymethyl-1α, 2α, 3α-trihydroxycyclopentanetriol.

Evidence for the intermediacy of a 4β-hydroxymethyl-1α, 2α, 3α-trihydroxycyclopentanetdol (5 or6) in the biosynthesis of the nucleoside antibiotic aristeromycin (1) has been obtained by administration of doubly-labeled forms of D-glucose to the fermentation broth ofStreptomyces citricolor followed by trapping of the tetrol5 using isotope dilution methods.     

Chlorination of α-sulfonyl carbanions with hexachloroethane: A novel preparation of α-halosulfones

The cyclic sulfones1,2, and3 are lithiated in benzene with n-butyllithium. Lithiation is demonstrated to lead to α-mono, α,α′-di and/or α,α-di and α,α,α′ trimetallation. The lithiated sulfones are chlorinated with hexachloroethane (HCE). Some mechanistic aspects of the reaction of the lithiosulfones with vicinal dihalides are discussed.     

Hydrogenation of β-Keto Sulfones to β-Hydroxy Sulfones with Alkyl Aluminum Compounds: Structure of Intermediate Hydroalumination Products

β-Hydroxy sulfones are important in organic synthesis. The simplest method of β-hydroxy sulfones synthesis is the hydrogenation of β-keto sulfones. Herein, we report the reducing properties of alkyl aluminum compounds R₃Al (R = Et, i-Bu, n-Bu, t-Bu and n-Hex); i-Bu₂AlH; Et₂AlCl and EtAlCl₂ in the hydrogenation of β-keto sulfones. The compounds i-Bu₂AlH, i-Bu₃Al and Et₃Al are the at best reducing agents of β-keto sulfones to β-hydroxy sulfones. In reactions of β-keto sulfones with aluminum trialkyls, hydroalumination products with β-hydroxy sulfone ligands [R₂AlOC(C₆H₅)CH₂S(O)₂(p-R¹C₆H₄]_n [where n = 1,2; 2aa: R = i-Bu, R¹ = CH₃; 2ab: R = i-Bu, R¹ = Cl; 2ba: R = Et, R¹ = CH₃; 2bb: R = Et, R¹ = Cl] and {[Et₂AlOC(C₆H₅)CH₂S(O)₂(p-ClC₆H₄]∙Et₃Al}_n 3bb were obtained. These complexes in the solid state have a dimeric structure, while in solutions, they appear as equilibrium monomer–dimer mixtures. The hydrolysis of both the isolated 2aa, 2ab, 2ba, 2bb and 3bb and the postreaction mixtures quantitatively leads to pure racemic β-hydroxy sulfones. Hydroalumination reaction of β-keto sulfones with alkyl aluminum compounds and subsequent hydrolysis of the complexes is a simple and very efficient method of β-hydroxy sulfones synthesis.     

A simple route to syn α-Amino-β-Hydroxy esters by C-2 regioselective opening of a, β-Epoxy esters with metal halides

α,β-Epoxy esters are opened by NaX (X = I, Br) in a regio and stereoselective fashion to β-hydroxy-α-halo esters, which represent suitable precursors of syn α-amino-β-hydroxy esters and β-hydroxy esters.     

New series of platinum group metal complexes bearing η- and η-cyclichydrocarbons and Schiff base derived from 2-acetylthiazole: Syntheses and structural studies

The mononuclear complexes [(η⁶-arene)Ru(ata)Cl]PF₆ {ata = 2-acetylthiazole azine; arene = C₆H₆ [(1)PF₆]; p-ⁱPrC₆H₄Me [(2)PF₆]; C₆Me₆ [(3)PF₆]}, [(η⁵-C₅Me₅)M(ata)]PF₆ {M = Rh [(4)PF₆]; Ir [(5)PF₆]} and [(η⁵-Cp)Ru(PPh₃)₂Cl] {η⁵-Cp = η⁵-C₅H₅ [(6)PF₆]; η⁵-C₅Me₅ (Cp^*) [(7)PF₆]; η⁵-C₉H₇ (indenyl); [(8)PF₆]} have been synthesised from the reaction of 2-acetylthiazole azine (ata) and the corresponding dimers [(η⁶-arene)Ru(μ-Cl)Cl]₂, [(η⁵-C₅Me₅)M(μ-Cl)Cl]₂, and [(η⁵-Cp)Ru(PPh₃)₂Cl], respectively. In addition to these complexes a hydrolysed product (9)PF₆, was isolated from complex (4)PF₆ in the process of crystallization. All these complexes are isolated as hexafluorophosphate salts and characterized by IR, NMR, mass spectrometry and UV–Vis spectroscopy. The molecular structures of [2]PF₆ and [9]PF₆ have been established by single-crystal X-ray structure analyses.     

η-Pentamethylcyclopentadienylruthenium(II) complexes containing η-coordinated α-amino acids

Reaction of [Cp* RuCl₂]₂ with -alanine ( -alaH) in methanol at room temperature in the presence of NaOMe yields the complex Na[Cp* RuCl( -ala)] (1), which contains a five-membered N,O-coordinated chelate ring. The analogous complex Na[Cp* RuCl( -phe)] (2) is obtained under similar conditions but at 0°C in 90% yield. At temperatures above 20°C both 2 and the η⁶-coordinated complex [Cp* Ru( -pheH)]Cl (4) are obtained, with the proportion of the latter increasing with temperature. Compound 4 is obtained in 88% yield by refluxing [Cp* RuCl₂]₂ and -phenylalanine ( -pheH) in CH₃OH/CH₃ONa followed by separation from 2. The analogous ruthenium(II) sandwich complexes 5–10 were obtained from -tyrosine and -tryptophane and various derivatives. [Cp* Ru( -met)] (3), prepared by the reaction of [Cp* RuCl₂]₂ with -methionine ( -metH) in CH₃OH/CH₃ONa, displays N,O,S-coordination.     

Synthesis of α,β-unsaturated oxathiolanes

The formation of α,β-unsaturated oxathiolanes 2 from α,β-unsaturated carbonyl derivatives was achieved selectively and in high yields using the heterogeneous catalyst APSG·HCl.     

Catalytic asymmetric epoxidation of α,β-unsaturated carboxylic acid imidazolides and amides by lanthanide–BINOL complexes

Highly enantioselective catalytic asymmetric epoxidation of α,β-unsaturated carboxylic acid imidazolides and simple amides was developed. In the presence of 5–10 mol% of lanthanide–BINOL complexes, the reaction proceeded smoothly with high substrate generality. In particular, in the cases of α,β-unsaturated amides, there was nearly perfect enantioselectivity (>99% ee). The corresponding epoxides were successfully transformed into many types of useful chiral compounds such as α,β-epoxy esters, α,β-epoxy amides, α,β-epoxy aldehydes, α,β-epoxy β-keto ester, and α- and β-hydroxy carbonyl compounds. B3LYP density functional studies were performed to predict substrate reactivity.     

Highly stereoselective aziridine ring-opening with phenylselenide anion and selective intramolecular aldol closure for the enantiopure synthesis of γ-aminocyclopentene derivatives

A practical and enantiopure synthesis for the preparation of key intermediates of conformationally locked γ-amino acid and nucleoside analogues is described. First, a highly stereoselective aziridine ring-opening reaction with phenylselenide anion was employed for the stereoselective synthesis of the chiral aminoselenide (1S,2S,1′S)-8, which after N-benzylation was transformed into the corresponding allyl amine (1S,1′S)-7 by oxidation with H₂O₂. Then, dihydroxylation–dehomologation of (1S,1′S)-7 with (OsO₄/NMO, NaIO₄) selectively afforded the desired γ-aminocyclopentene aldehyde (S)-1 and its corresponding γ-amino acid (S)-2 via an intramolecular selective aldol-condensation catalyzed by an internal base.     

LnCl3(cat.)/Zn promoted hydroperfluoroalkylation of αβ - unsaturated esters with perfluoroalkyl iodides

LnCl₃(cat.)/Zn system has been found to cause hydroperfluoro-alkylation of α,β - unsaturated esters with perfluoroalkyl iodides in high yields as compared with the reaction with Zn alone.