Lithiated γ-O-functionalized propyl phenyl sulfides and sulfones of the type Li[CH(SOxPh)CH2CH2OR] (x = 0, 2). [Li{CH(SPh)CH2CH2Ot-Bu}(tmeda)] – A structurally characterized organolithium inner complex

Lithiation of O-functionalized alkyl phenyl sulfides PhSCH₂CH₂CH₂OR (R = Me, 1a; i-Pr, 1b; t-Bu, 1c; CPh₃, 1d) with n-BuLi/tmeda in n-pentane resulted in the formation of α- and ortho-lithiated compounds [Li{CH(SPh)CH₂CH₂OR}(tmeda)] (α-2a–d) and [Li{o-C₆H₄SCH₂CH₂CH₂OR)(tmeda)] (o-2a–d), respectively, which has been proved by subsequent reaction with n-Bu₃SnCl yielding the requisite stannylated γ-OR-functionalized propyl phenyl sulfides n-Bu₃SnCH(SPh)CH₂CH₂OR (α-3a–d) and n-Bu₃Sn(o-C₆H₄SCH₂CH₂CH₂OR) (o-3a–d). The α/ortho ratios were found to be dependent on the sterical demand of the substituent R. Stannylated alkyl phenyl sulfides α-3a–c were found to react with n-BuLi/tmeda and n-BuLi yielding the pure α-lithiated compounds α-2a–c and [Li{CH(SPh)CH₂CH₂OR}] (α-4a–b), respectively, as white to yellowish powders. Single-crystal X-ray diffraction analysis of [Li{CH(SPh)CH₂CH₂Ot-Bu}(tmeda)] (α-2c) exhibited a distorted tetrahedral coordination of lithium having a chelating tmeda ligand and a C,O coordinated organyl ligand. Thus, α-2c is a typical organolithium inner complex.Lithiation of O-functionalized alkyl phenyl sulfones PhSO₂CH₂CH₂CH₂OR (R = Me, 5a; i-Pr, 5b; CPh₃, 5c) with n-BuLi resulted in the exclusive formation of the α-lithiated products Li[CH(SO₂Ph)CH₂CH₂OR] (6a–c) that were found to react with n-Bu₃SnCl yielding the requisite α-stannylated compounds n-Bu₃SnCH(SO₂Ph)CH₂CH₂OR (7a–c). The identities of all lithium and tin compounds have been unambiguously proved by NMR spectroscopy (¹H, ¹³C, ¹¹⁹Sn).     

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.     

Synthesis and structure of the unsymmetrical β-diimine precursor: The β-iminoamine

The reaction of benzoylacetone with ortho-substituted aniline derivatives gives the unsymmetrical β-iminoamine ligands (5–8) with high yields. A convenient synthesis is described. These compounds have been characterized by NMR and IR spectroscopies. The structure of the β-iminoamine 5, 3-N-(2,6-diisopropylphenylamino)-1-phenyl-1N-(2,6-diisopropylphenylimino)but-2-ene, was solved by X-ray diffraction 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.     

α-Fluoro decalones as chiral epoxidation catalysts: fluorine effect

Three rigid monofluorinated trans-decalones 4a, 5e, and 6e (90% ee) have been synthesized from commercially available (−)-(R)-methyl naphthalenone (90% ee). Their structures have been fully characterized (NMR, X-ray): ketones 4a and 5e are Me,F-disubstituted α to the carbonyl with the fluorine axial and equatorial, respectively, while ketone 6e is F-monosubstituted α to the carbonyl with the fluorine equatorial. The use of these ketones as chiral catalysts for the epoxidation of trans-olefins (such as stilbene, β-methylstyrene and p-methoxy cinnamate) through the formation of dioxiranes shows (i) that dioxiranes with an equatorial fluorine α to the dioxirane ring are less reactive and provide lower ee’s than dioxiranes with an axial fluorine and having the same chirality and (ii) that an axial methyl α to the dioxirane ring is significantly less efficient than a fluorine. The results corroborate Armstrong and Houk’s theoretical model and our first hypothesis to rationalize the inverted enantioselectivities observed using α-fluorinated cyclohexanones having the same chirality, i.e.: rapid ring inversion (Curtin–Hammett principle) allows the dioxirane conformation to have the fluorine axial (even if less populated than the other) to contribute significantly to the epoxidation reaction.     

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.     

Synthesis and unusual beckmann fragmentation reaction of syn-3-Methoxy-6α,17β-Dihydroxyestra-1,3,5(10)-trien-7-one oxime

Sodium borohydride reduction of anti-3-methoxy-17β-hydroxyestra-1,3,5(10)-trien-6,7-dione 7-oxime (4a) afforded syn-3-methoxy-6α,17β-dihydroxyestra-1,3,5(10)-trien-7-one oxime (5), which in thionyl chloride at −18 °C undenvent Beckmann fragmentation reaction to the unexpected 3-methoxy-6-oxo-17β-hydroxy-6.7-secoestra-1.3.5(10)-trien-7-nitrile (6). A mechanism of this fragmentation process was proposed.     

η-Alkynyl and vinylidene transition metal complexes: 10. Reaction of the metal-acetylide [(η-C5H5)(CO)(NO)W---CC---C(CH3)3]Li with 1,2-diiodoethane as electrophile and with various nucleophiles

Treatment of the η¹-acetylide complex [(η⁵-C₅H₅)(CO)(NO)W---CC---C(CH₃)₃]Li (4) with 1,2-diiodoethane in THF at −78 °C, followed by the addition of Li---CC---R [R=C(CH₃)₃, C₆H₅, Si(CH₃)₃, 6a–6c] or n-C₄H₉Li and protonation with H₂O, afforded the corresponding oxametallacyclopentadienyl complexes (η⁵-C₅H₅)W(I)(NO)[η²-O=C(CC---R)CH=CC(CH₃)₃] (7a–7c), 8c and (η⁵-C₅H₅)W(I)(NO)[η²-O=C(n-C₄H₉)CH=CC(CH₃)₃] (9). The formation of these metallafuran derivatives is rationalized by the electrophilic attack of 1,2-diiodoethane onto the metal center of 4 to form first the neutral complex [(η⁵-C₅H₅)(I)(CO)(NO)W---CC---C(CH₃)₃] (5). Subsequent nucleophilic addition of Li---CC---R 6a–6c or n-C₄H₉Li and a reductive elimination step followed by protonation leads to the products 7a–7c and 9. One reaction intermediate could be trapped with CF₃SO₃CH₃ and characterized by a crystal structure analysis. The identity of another intermediate was established by infrared spectroscopic data. The oxametallacyclopentadienyl complex 10 forms in the presence of excess 1,2-diiodoethane through an alternative pathway and crystallizes as a clathrate containing iodine.     

A practical and enantiospecific conversion of d-galactose to a substituted α,β-unsaturated δ-lactone synthon

A multi-gram synthesis of a substituted α,β-unsaturated δ-lactone synthon, 1, was developed from commercially available d-galactose. The use of a Horner–Wadsworth–Emmons reaction was able to furnish, with Z selectivity, the enone ester that spontaneously lactonised to provide enantiomerically pure 1.     

Neutron diffraction study of the β′ and γ phases of LiFeO2

The β, β′, γ and α phases of LiFeO₂, synthesized as powders, were annealed at different temperatures and characterized by X-ray measurements. The β′ and γ modifications were also studied by time-of-flight neutron diffraction (ISIS Facility, UK). The structure of the β′ phase was refined in the monoclinic C2/c space group (a=8.566(1), b=11.574(2), c=5.1970(5) Å, β=146.064(5)°) to wR_p=0.071–0.080 (data from four counter banks). Fe and Li atoms are ordered over two of the four independent sites, and partially disordered over the other two. The ordered Li has a distorted tetrahedral coordination. The γ structure was refined at RT (a=4.047(1), c=8.746(2) Å) and at 570 °C (a=4.082(3), c=8.822(6) Å) in the I4₁/amd symmetry, showing full order with Li in octahedral coordination at RT, and in a split-atom configuration at high temperature. On annealing, the β′ polymorph was found to transform to γ at 550 °C, thus suggesting that it is a metastable phase. Electrostatics is discussed as the driving force for the α→β′→γ ordering process of LiFeO₂.     

Solid state coordination chemistry of copper(II)/α-hydroxycarboxylato/2,2′-bipyridine systems

Four new two-ligand complexes of copper(II) with 2,2′-bipyridine and one of three different α-hydroxycarboxylic acids (lactic, H₂LACO; 2-methyllactic, H₂MLACO; and mandelic, H₂MANO) were prepared. Complexes 1–3 of general formula [Cu(HL)₂(bipy)]·nH₂O (HL=monodeprotonated acid), were characterized by elemental analysis, IR, electronic and EPR spectroscopy, magnetic measurements and thermogravimetric analysis. Complexes 1 (HL=HLACO, n=2), 2 (HL=HMLACO, n=1) and 3a (the result of attempted recrystallization of 3, of formula [Cu(HMANO)(bipy)₂](HMANO)·H₂MANO·CH₃CN were studied by X-ray diffractometry. The copper atom is in an elongated, tetragonally distorted octahedral environment in 1 and 2 and in 3a has a coordination polyhedron intermediate between a square pyramid and a trigonal bipyramid, as evaluated in terms of the parameter τ. In 1 and 2 the α-hydroxycarboxylato ligand is bidentate and monoanionic but in 3a there are three forms: a monodentate monoanion, a monoanionic counterion, and a neutral molecule.     

Unusual stabilization of cationic “M(η-allyl) (M = Pt, Pd) units by a dianionic cis-{Pt(C6F5)2(CCSiMe3)2} fragment

Chloride abstraction from [{M(η³ --- C₃H₅)Cl}_n] (M = Pt, n = 4 or M = Pd, n = 2) by (NBu₄)₂[cis-Pt(C₆F₅)₂(CCSiMe₃)₂] (1) gives rise to novel homo- and hetero-dinuclear zwitterionic derivatives (NBu₄) [{cis-Pt(C₆F₅)₂(CCSiMe₃)₂}M(η³-C₃H₅)] (M = Pt 2; M = Pd 3) which are formed by a M(η³-allyl)⁺ unit attached to both alkynyl ligands of the {cis-Pt(C₆F₅)₂(CCSiMe₃)₂}²⁻ fragment. The structure of 3 has been established by X-ray diffraction.     

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).     

Theoretical investigation on possible mechanisms on regioselective formation of (η-siloxyallyl)tungsten complexes

Selective formation of (η³-siloxyallyl)tungsten complexes by reaction of hydrido(hydrosilylene)tungsten complexes with α,β-unsaturated carbonyl compounds was reported experimentally. The mechanisms have been investigated by employing the model reaction of [Cp(CO)₂(H)WSi(H)–{C(SiH₃)₃}] (R), derived from the original experimental complex Cp′(CO)₂(H)WSi(H)–[C(SiMe₃)₃] (1a, Cp′ = Cp*; 1b, Cp′ = η⁵-C₅Me₄Et), with methyl vinyl ketone, under the aid of the density functional calculations at the b3lyp level of theory. It is theoretically predicted that the route involving migration of the hydride to silicon to afford a 16e intermediate [Cp(CO)₂W–SiH₂–{C(SiH₃)₃}] is inaccessible (route 2), supporting the proposition by experiments. Another route, via [2 + 4] cycloaddition followed by directly Si–H reductive elimination, is theoretically predicted to be accessible (route 1). In route 1, two possible paths with different attacking directions of the oxygen of methyl vinyl ketone at Si (WSi) are put forward. The attack at the Si atom from the hydride (H1) side of the plane W–Si–H1 in R is found to be preferred kinetically. The regioselectivity for formation of (η³-siloxyallyl)tungsten complexes, where only the exo-anti isomer was obtained, is discussed based on the consideration of thermodynamics and kinetics.     

Asymmetric oxidation of enol phosphates to α-hydroxy ketones by (salen)manganese(III) complex. Effects of the substitution pattern of enol phosphates on the stereochemistry of oxygen transfer

This paper presents a study of enantioselective catalytic oxidation of a variety of differently substituted, cyclic (E) and acyclic (Z)-enol phosphates. The asymmetric oxidation of acyclic (Z)-enol phosphates containing alkoxy substituents in the phosphate group 2a, c, e–g, i, and j and Z-configured enol phosphates containing aryloxy substituents in the phosphate group 2b, d, and h afforded optically active α-hydroxy ketones 4a–j of opposite configuration with good to high enantioselectivity. The influence of electronic and steric effects of the enol phosphate substituents on the stereoselectivity of oxidation was studied.     

Synthesis, structure and DNA binding studies of mononuclear copper(II) complexes with mixed donor macroacyclic ligands, 2,6-bis({N-[2&3-(phenylselenato)alkyl]}benzimidoyl)-4-methylphenol

Two new phenol based macroacyclic Schiff base ligands, 2,6-bis({N-[2-(phenylselenato)ethyl]}benzimidoyl)-4-methylphenol (bpebmpH, 1) and 2,6-bis({N-[3-(phenylselenato)propyl]}benzimidoyl)-4-methylphenol (bppbmpH, 2) of the Se₂N₂O type have been prepared by the condensation of 4-methyl-2,6-dibenzoylphenol (mdbpH) with the appropriate (for specific reactions) phenylselenato(alkyl)amine. These ligands with Cu(II) acetate monohydrate in a 2:1 molar ratio in methanol form complexes of the composition [(C₆H₂(O)(CH₃){(C₆H₅)CN(CH₂)_nSe(C₆H₅)}{(C₆H₅)CO}₂Cu] (3 (n = 2), 4 (n = 3)) with the loss of phenylselenato(alkyl)amine and acetic acid. In both these complexes, one arm of the ligand molecule undergoes hydrolysis, and links with Cu(II) in a bidentate (NO) fashion, as confirmed by single crystal X-ray crystallography of complex 3. The selenium atoms do not form part of the copper(II) distorted square planar coordination sphere which has a trans-CuN₂O₂ core. The average Cu–N and Cu–O distances are, respectively, 1.973(3) and 1.898(2) Å. The N–Cu–N and O–Cu–O angles are, respectively, 167.4(11)° and 164.5(12)°. The compounds 1–4 have been characterized by elemental analysis, conductivity measurements, mass spectrometry, IR, electronic, ¹H and ⁷⁷Se{¹H} NMR spectroscopy and cyclic voltammetry. The interaction of complex 3 with calf thymus DNA has been investigated by a spectrophotometric method and cyclic voltammetry.     

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.     

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.     

A highly stereoselective synthesis of α,β-unsaturated oxazolines

Lithiated 2,4,4-trimethyl-2-oxazoline 2a and 2-chloromethyl-4,4-dimethyl-2-oxazoline 2b react smoothly with a number of nitrones 3 to produce α,β-unsaturated oxazolines 6 and 7 highly stereoselectively.