Alkene insertion reactions of nitrogen-coordinated acylpalladium(II) complexes. The crystal structure of the dicyclopentadiene insertion product [Pd(C10H12COMe)(bpy)]SO3CF3

The new acylpalladium(II) complex [PdI(COMe)(bpy)] (2b, bpy = 2,2′-bipyridyl) has been obtained by two routes; (i) by insertion of carbon monoxide into the PdC bond of [PdIMe(bpy)] (1b), and (ii) by ligand exchange from [PdI(COMe)(tmeda)] (2a, tmeda = N,N,N′,N′-tetramethylethanediamine). The cationic species obtained by reaction of 2a and 2b with AgOSO₂CF₃ both undergo alkene insertions into the PdC acyl bond that lead to remarkably stable products. The X-ray structure of the dicyclopentadiene insertion product [Pd(C₁₀H₁₂COMe)(bpy)]SO₃CF₃ (4b) shows the oxygen atom of the carbonyl group to be coordinated to the metal center (PdO = 2.026(3) Å).     

Advanced procedure for the enzymatic ring opening of unsaturated alicyclic β-lactams

Enantiopure β-amino acids 1a–4a and β-lactams 1b–4b were prepared simultaneously through the lipolase-catalysed enantioselective ring opening of unsaturated racemic β-lactams (±)-1-(±)-4. High enantioselectivities (E>200) were observed when the reactions were performed with 1 equiv of water in iPr₂O at 70 °C. The resolved (1R,2S)-amino acids (yield⩾45%) and (1S,5R)-, (1S,6R)- and (1S,8R)-lactams (yield⩾47%) could be easily separated. The ring opening of lactam enantiomers 1b–4b with 18% HCl afforded the corresponding β-amino acid hydrochlorides 1c·HCl–4c·HCl (ee >95%).     

Synthesis of eight-membered iminocyclitols from d-glucose

The Baylis-Hillman reaction of 3-O-benzyl-α-d-xylo-pentodialdo-1,4-furanose 2 afforded a diastereomeric mixture of l-ido- and d-gluco-configurated α-methylene-β-hydroxy esters 3a and 3b, respectively, in 1:1 ratio. Conjugate addition of benzyl amine on 3a gave adduct 4a as a major product while, addition of benzyl amine to 3b gave only one diastereomer 4b. Reduction of ester functionality in 4a/4b, opening of 1,2-acetonide functionality followed by reductive amino-cyclization under hydrogenation condition afforded azocanes 1c/1d in good yield.     

Gold(I) N-heterocyclic carbene based initiators for bulk ring-opening polymerization of l-lactide

Synthesis, structures, and catalysis studies of gold(I) complexes of N-heterocyclic carbenes namely, a di-O-functionalized [1-(2-hydroxy-cyclohexyl)-3-(acetophenone)imidazol-2-ylidene], a mono-O-functionalized [1-(2-hydroxy-cyclohexyl)-3-(benzyl)imidazol-2-ylidene] and a non-functionalized [1,3-di-i-propyl-benzimidazol-2-ylidene], are reported. Specifically, the gold complexes, [1-(2-hydroxy-cyclohexyl)-3-(acetophenone)imidazol-2-ylidene]AuCl (1c), [1-(2-hydroxy-cyclohexyl)-3-(benzyl)imidazol-2-ylidene]AuCl (2c), and [1,3-di-i-propyl-benzimidazol-2-ylidene]AuCl (3b), were prepared from the respective silver complexes 1b, 2b, and 3a by treatment with (SMe₂)AuCl in good yields following the commonly used silver carbene transfer route. The silver complexes 1b, 2b, and 3a were synthesized from the respective imidazolium halide salts by the reactions with Ag₂O. The N-heterocyclic carbene precursors, 1-(2-hydroxy-cyclohexyl)-3-(acetophenone)imidazolium chloride (1a) and 1-(2-hydroxy-cyclohexyl)-3-(benzyl)imidazolium chloride (2a), were synthesized by the direct reactions of cyclohexene oxide and imidazole with chloroacetophenone and benzyl chloride respectively. The gold (1c, 2c, and 3b) and the silver (3a) complexes along with a new O-functionalized imidazolium chloride salt (1a) have been structurally characterized by X-ray diffraction. The structural studies revealed that geometries around the metal centers were almost linear in these gold and silver complexes. The gold (1c, 2c, and 3b) complexes efficiently catalyze ring-opening polymerization (ROP) of l-lactide under solvent-free melt conditions producing polylactide polymer of moderate to low molecular weights with narrow molecular weight distributions.     

Clathrate formation of Diels–Alder adduct of phencyclone and acenaphthylene. Key role of CH/π and bidentate CH/O interactions of the phenanthrene ring in construction of host framework

Two clathrate hosts (3a and 3b) were synthesized via the Diels–Alder reaction of phencyclone (1a) and tetracyclone (1b) with acenaphthylene (2), and the clathrate formation properties of these hosts towards a variety of organic guests were investigated. In the presence of aprotic solvents (i.e., aromatic, ketonic and etheric solvents), host 3a formed inclusion complexes with a 2:1 stoichiometric host/guest ratio, whereas 3b primarily formed 1:1 complexes. The desolvation temperatures of the 3a·guest complexes were extremely high in comparison to the boiling points of the pure guest liquids and were also much higher than those of the corresponding 3b·guest complexes, which contain the conformationally flexible stilbene moiety. Structural analyses of the 3a·guest complexes (i.e., 3a·benzene, 3a·toluene, 3a·1,4-dioxane, 3a·acetone and 3a·pentan-3-one) show that the aromatic CH/π (edge-to-face) interactions between phenanthrene and the acenaphthene ring as well as the interaction of the ‘bidentate’ CH/O hydrogen bond between the phenanthrene-ring hydrogen and the bridged carbonyl oxygen play a key role in the construction of the characteristic host ‘column’ structures. The guest molecule of the 3a·benzene complex is held between the stacking columns by aromatic CH/π interactions of the acenaphthene rings of adjacent host molecules. The stable clathrate formation of 3a is discussed based on X-ray structural analyses of six clathrates and PM6 molecular orbital calculations for the clathration model of 3a·benzene.     

Cyclic tautomers of tryptophans and tryptamines—4: Synthesis of cyclic tautomers of tryptophans and tryptamines

N_b-Methoxycarbonyltryptophan methyl ester (dl- and l-13) was cyclized to the corresponding rans cyclic tautomer (14) in excellent yield in various acids such as 85% phosphoric acid or trifluoroacetic acid. The cis cyclic tautomer (15) was formed as the less stable and kinetically controlled product and converted to the more stable trans isomer (14) under the reaction condition. The trans isomer (14) was reverted to 13 on treatment with 10% sulfuric acid in methanol. Other tryptophan and tryptamine derivatives (6 and 19a) also cyclized to the corresponding cyclic tautomers in similar acidic media.     

Synthesis of tubuphenylalanine and epi-tubuphenylalanine via regioselective aziridine ring opening with carbon nucleophiles followed by hydroboration-oxidation of 1,1-substituted amino alkenes

An efficient synthesis of N-Boc-tubuphenylalanine benzyl ester (N-Boc-Tup-OBn, 1a) and N-Boc-epi-tubuphenylalanine benzyl ester (N-Boc-epi-Tup-OBn, 1b) is reported herein. Regioselective aziridine 4 ring opening with carbon nucleophiles followed by hydroboration of 1,1-substituted aminoalkene 3 using 9-BBN and subsequent oxidation in an alkaline medium are used as the key steps to provide N-tosyl 1,4-aminoalcohols. The 1,4-aminoalcohols are successfully transformed into the desired products with an overall yield of 23% for 1a and 11% for 1b over 8 consecutive steps separately.     

Recognition of linear and bent forms of solid μ-oxo-bis[iodotriphenylantimony(V)] (Ph3SbI)2O

Two quite different shapes of the (Ph₃SbI)₂O molecule are found in separate crystals, namely 1a, in which the SbOSb bridge is linear with bond distances of 1.9410–1.9437(6) Å and 1b in which the SbOSb angle is 144.6(4)° and the SbO bonds are longer, averaging 1.971(8) Å. The two species also give distinct vibrational spectra. Both arise from the reaction of triphenylantimony with iodine in moist acetonitrile, 1a as the initial crop of colourless crystals and 1b as organe crystals left when the solution is allowed to evaporate to dryness.     

Pseudopolymorphs of chelidamic acid and its dimethyl ester

Different tautomeric and zwitterionic forms of chelidamic acid (4‐hydroxypyridine‐2,6‐dicarboxylic acid) are present in the crystal structures of chelidamic acid methanol monosolvate, C₇H₅NO₅·CH₄O, (Ia), dimethylammonium chelidamate (dimethylammonium 6‐carboxy‐4‐hydroxypyridine‐2‐carboxylate), C₂H₈N⁺·C₇H₄NO₅⁻, (Ib), and chelidamic acid dimethyl sulfoxide monosolvate, C₇H₅NO₅·C₂H₆OS, (Ic). While the zwitterionic pyridinium carboxylate in (Ia) can be explained from the pK_a values, a (partially) deprotonated hydroxy group in the presence of a neutral carboxy group, as observed in (Ib) and (Ic), is unexpected. In (Ib), there are two formula units in the asymmetric unit with the chelidamic acid entities connected by a symmetric O—H...O hydrogen bond. Also, crystals of chelidamic acid dimethyl ester (dimethyl 4‐hydroxypyridine‐2,6‐dicarboxylate) were obtained as a monohydrate, C₉H₉NO₅·H₂O, (IIa), and as a solvent‐free modification, in which both ester molecules adopt the hydroxypyridine form. In (IIa), the solvent water molecule stabilizes the synperiplanar conformation of both carbonyl O atoms with respect to the pyridine N atom by two O—H...O hydrogen bonds, whereas an antiperiplanar arrangement is observed in the water‐free structure. A database study and ab initio energy calculations help to compare the stabilities of the various ester conformations.     

Synthesis of 4-aryl-substituted β-lactam enantiomers by enzyme-catalyzed kinetic resolution

Enantiopure 4-phenyl- and 4-(p-tolyl)-2-azetidinones 3a, 3b, 4a and 4b (with e.e.s of ≥96%) were prepared through lipase-catalyzed asymmetric butyrylation of the primary OH group of N-hydroxymethylated β-lactams (±)-5 and (±)-6 at the (R)-stereogenic centre or by lipase-catalyzed asymmetric debutyrylation of O-butyryloxymethyl-2-azetidinones (±)-7 and (±)-8 at the (R)-stereogenic centre. The ring-opening of lactams 5a, 5b, 6b and 8a with HCl/EtOH afforded the corresponding β-amino ester enantiomers 9a, 9b, 10a and 10b with e.e.s of ≥92%.     

Synthese und reaktivität von silicium-übergangsmetall-komplexen: XVIII. Trihydrosilylkomplexe des eisens: Darstellung und metallierung mit dicobaltoctacarbonyl

The reaction of the silyl complex Cp(CO)₂FeSiH₃ (1) with various donors under photochemical conditions leads to the formation of Cp(CO)(L)FeSiH₃ (2a-2c) and Cp(L)₂FeSiH₃ (3a, 3b) (L = MeNC, t-BuNC, Me₃P) via stepwise CO-substitution. 2a,2b are transformed by Co₂(CO)₈ to the complexes μ₂-[Cp(CO)-(RNC)FeSiH] [μ²-(CO)] Co₂(CO)₆ (3a,3b), the first complexes with a hydrogen substituted ferrio-silanediyl unit bridging two cobalt atoms.     

Zur Kenntnis der Struktur der Chalkon-Guanidin-Kondensate Über Heterocyclen, 75. Mitt.

Guanidine reacts with chalkone1 a, 4-methylchalkone1 b and 4′-methylchalkone1 c resp. to yield mixtures of pyrimidinamines2 a,3 b and3 c (=3 b) resp. with (2:1)-condensatesA,B andC resp. The structures of the compoundsA-C (whicha priori could be dihydropyrimidopyrimidines4 a-c or5 a-c or6 a-c) are elucidated. NMR-investigations show that the saltsA-C · HCl must be symmetrically substituted pyrimidopyrimidinyliumchlorides4 a-c · HCl or5 a-c · HCl (and not6 a-c · HCl). Furthermore, it is proved by chemical methods that the condensatesB · HCl andC · HCl are pyrimidopyrimidinyliumchlorides4 b andc · HCl (and not5 b andc · HCl): The structure ofB · HCl (=4 b · HCl) was established by total synthesis of dimethylpyrimidopyrimidinyliumpicrate9 b-Pi from10 c (via13 c · HI-18 · HCl) and transformation ofB · HCl into an identical salt9 b-Pi via hexahydropyrimidopyrimidine8 b · HCl. The structure ofC · HCl (=4 c · HCl) was determined by comparison of its hydrogenation product (=8c · HCl) with8 b · HCl. The structure of condensateA · HCl (=4 a · HCl) results from conclusion by analogy. The spatial structure of4 a-c · HCl and8 a-c · HCl is discussed; it was established by NMR that the salts are racemic mixtures of stereoisomers4 a-c K · HCl and8 a-c K · HCl resp. and their antipodes (with C₂ symmetry).     

Five- and six-membered palladacycles derived from [(η5-C5H5)Fe{(η5-C5H4)-CH=N-(C6H4-2-C6H5)}]

The reaction of the novel ferrocenyl Schiff base: [(η⁵-C₅H₅)Fe{(η⁵-C₅H₄)-CH=N-(C₆H₄-2-C₆H₅)}] (1) with Na₂[PdCl₄] and Na(CH₃COO)·3H₂O in a 1:1:1 molar ratio in methanol is reported. In this reaction two different di-μ-chloro-bridged cyclopalladated complexes: [Pd{[(η⁵-C₅H₃)-CH=N-(C₆H₄-2-C₆H₅)]Fe(η⁵-C₅H₅)}(μ-Cl)]₂ (2a) and [Pd{[(C₆H₄-2-C₆H₄)-N=CH-(η⁵-C₅H₄)]Fe(η⁵-C₅H₅)}(μ-Cl)]₂ (2b) can be formed depending on the experimental conditions. Compounds 2a and 2b, which differ in the nature of the metallated carbon atom (C_{sp²,ferrocene} or C_{sp²,biphenyl}, respectively), undergo cleavage of the ‘Pd(μ-Cl)₂Pd’ bridges in the presence of thallium (I) acetylacetonate, deuterated pyridine or triphenylphosphine giving the monomeric derivatives: [Pd(C^∧N)(acac)] (3a, 3b) and [Pd(C^∧N)Cl(L)] {with L=py- d₅(4a, 4b), PPh₃(5a, 5b)}. The reactions of 2 with 1,2-bis(diphenylphosphino)ethane (dppe) reveal that the two isomers (2a and 2b) exhibit different reactivity versus dppe. These results have been interpreted on the basis of steric effects.     

Synthesis and characterization of new (pyrazolyl)aryl phosphinite PCN pincer palladium(II) complexes

Two unsymmetrical PCN pincer Pd(II) complexes 3a–3b which are based on (pyrazolyl)aryl phosphinite ligands and contain two fused six-membered palladacycles have been synthesized from 3-(3,5-dimethylpyrazol-1-ylmethyl)benzyl alcohol (2) by one-pot phosphorylation/palladation reaction via C–H bond activation of the related ligands. The pyrazole-coordinated phosphine-free Pd(II) complex (4) was also isolated in the preparation of pincer complex 3a. The new complexes were characterized by elemental analysis, ¹H NMR, ¹³C NMR, ³¹P {¹H} NMR (for pincer complexes) and IR spectra. And the molecular structures of 3b and 4 have been further determined by X-ray single-crystal diffraction. The pincer Pd complexes 3a and 3b exhibited rather low activity in the allylation of benzaldehyde.     

Application of the asymmetric hydrogenation of enamines to the preparation of a beta-amino acid pharmacophore

(3R)-3-[N-(tert-Butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)butanoic acid 7a has been synthesized by an asymmetric hydrogenation of enamine ester 3 using chiral ferrocenyl ligands I and II in conjunction with [Rh(COD)Cl]₂. The direct reduction of 3 provides amino ester 1b in 93% ee, which was isolated as an (S)-camphorsulfonic acid salt to upgrade the enantiomeric excess to >99%. A more concise approach was developed involving the in situ protection of 1b using di-tert-butyldicarbonate. This approach provided the desired N-Boc amino ester 7b directly from the hydrogenation with 97% ee, which was upgraded to >99% ee upon crystallization.     

Metal complexes of anionic 3-borane-1-alkylimidazol-2-ylidene derivatives

Addition of BH₃·thf to 1-alkylimidazoles (alkyl=methyl, butyl) and 1-methylbenzimidazole leads to BH₃ adducts, which are deprotonated by BuLi to yield the organolithium compounds (L)Li⁺(1b–d)⁻. In the solid state (thf)Li⁺1b⁻ is dimeric. The acyl–iron complexes (thf)₃Li⁺(3b,d)⁻ are formed from (thf)Li⁺(1b,d)⁻ and Fe(CO)₅. (L)Li⁺(1a–c)⁻ react with [CpFe(CO)₂X], however, the only complex obtained is [CpFe(CO)₂1a] (5a). The analogous reaction of (L)Li⁺1a⁻ with the pentadienyl complex [(C₇H₁₁)Fe(CO)₂Br] yields the corresponding iron compound 6a. Their compositions follow from spectroscopic data. Treatment of Cp₂TiCl with (L)Li⁺1a⁻ leads to [Cp₂Ti1a] (7a), which could not be oxidized with PbCl₂ to give the corresponding Ti(IV) complex. The compounds [Li(py)₄]⁺9a⁻ and [Li(L)₄]⁺(10b–d)⁻ are obtained when (L)Li⁺1⁻ are reacted with VCl₃ and ScCl₃. The X-ray structure analysis of the vanadium complex reveals a distorted tetrahedron of the anion [V(1a)₄]⁻ with two smaller and four larger CVC angles. The scandium compound [Li(dme)₂⁺10c⁻] has a different structure: the distorted tetrahedron of the anion [Sc(1c)₄]⁻ contains two larger (140.2 and 142.9°) and four smaller CScC angles (93.9–98.7°). This arrangement allows the formation of four bridging BHSc 3c,2e bonds to give an eight-fold coordination. The anion 10c⁻ is formally a 16e complex.     

Cleavage and some modifications of the 7-amide group of the cephamycins

The cleavage and some modifications of the 7-amide group of cephamycins are described. Cephamycin derivatives 16b, c which were synthesized from the naturally occurring cephamycin C (16a) were converted to the corresponding oxamic acid derivatives 17a, e respectively by the reaction with oxalyl chloride and successive treatment with water. The reaction of the oxamic acid 17a with diphenylcarbodiimide gave 7-aminocephamycinoic acid (7-ACMA) benzhydryl ester (21a) which was further converted to cefoxitin (21c). These compounds 17a, b, c, d, e, f thus obtained from cephamycin C appear to be favorable intermediates for the syntheses of cephamycin analogues such as cefmetazole (28c).     

Synthesis and structure of the heterotrinuclear chromium-palladium clusters (RC5H4CrCl)2-(μ3S)(μ-SCMe3)2Pd(PPh3) with ferromagnetic exchange interactions over the CrSCr system

Reactions of (RC₅H₄)₂Cr₂(SCMe₃)₂S(I, R = H; II, R = Me) with (PPh₃)₂PdCl₂ in benzene at 20°C gives trinuclear complexes (RC₅H₄)₂Cr₂Cl₂(μ₃-S)(μ-SCMe₃)₂Pd(PPh₃)(III, R = H; IV, R = Me). The structure of IV as a monobenzene solvate is established by an X-ray analysis (black-green triclinic crystals space group P$\text{1}$ with a = 11.403(4), b = 14.933(5), c = 14.131(5) Å, α = 99.13(3), β = 112.72(3), γ = 95.65(3)°, V = 2201.6 Å, Z = 2; IV·C₆H₆). The structure was solved by direct methods and refined in an anisotropic approximation to R = 0.046, R_w = 0.058 for 7643 reflections with I ? 2σ(I). In the molecule of IV metal atoms are separated by non-bonding distances (Cr … Cr 4.079(I), Cr … Pd 3.230(I) and 3.380(I) Å) but linked by the bridging tridentate sulphur atom (CrS 2.339(2) and 2.329(2), PdS 2.327(2) Å), and two SCMe₃ groups between Pd and Cr (CrS 2.396(2) and 2.403(2), PdS 2.350(2) and 2.381(2) Å, Cr?Pd 85.14(6) and 89.92(6)°). The Cl atoms are transferred from Pd to Cr atoms (CrCl 2.308(2) Å) and being terminally coordinated are in trans-positions to each other (as well as η-CH₃C₅H₄ rings) with respect to the Cr₂Pd plane. Cr atoms in III and IV exhibit ferromagnetic exchange interactions over the Cr?Cr system (+2J = 28 and 11 cm^?1, respectively).     

Pyrroles and related compounds—XXXIV : Acrylic esters in the porphyrin series

Treatment of imidazolylporphyrins (12) with sodium borohydride in methanol affords high yields of the corresponding hydroxymethylporphyrins (14) which can be oxidised with chromium trioxide in pyridine to give high yields of formylporphyrins (11). When heated with methyl hydrogen malonate in pyridine, good yields of porphyrin trans-acrylic esters (15) are produced; a milder method involving reaction of the formylporphyrin (11a) with a phosphonium ylid (20) or better, a phosphonate ester (21), gives good yields of the porphyrin trans-acrylic ester (16a).Porphyrin β-keto-esters (e.g. 8b) are reduced with sodium borohydride in methanol, to give the 6-hydroxypropionate ester (17b); prolonged treatment with borohydride results in over-reduction at the 7-propionate side-chain. The hydroxypropionate porphyrin (17b) is readily dehydrated to give a high yield of the porphyrin trans-acrylic ester (15b). Methods for the magnesiation and preparation of β-keto-ester and trans-acrylic ester porphyrin 7-propionic acids are described; hydrolysis of porphyrin β-keto-esters (e.g. 8b) can be controlled such that only the propionic function is hydrolysed. However, prolonged alkaline hydrolysis and re-esterification furnishes a mixture of 2-vinylrhodoporphyrin-XV dimethyl ester (9b) and the 2-vinyl-6-acetylporphyrin (18b). The latter porphyrin can also be prepared by treatment of the acid chloride (10b) from 2-vinylrhodoporphyrin-7-methyl ester with sodio di-t-butyl malonate, followed by treatment with trifluoroacetic acid.     

Solid-phase synthesis of core 2 O-linked glycopeptide and its enzymatic sialylation

The core 2-type tetrasaccharide building blocks (1a/1b) for solid-phase synthesis of glycopeptide were synthesized via stereoselective glycosylation of the disaccharyl Ser/Thr (3a/3b) with a glycosyl fluoride (2) carrying the 2-trichloroacetamido group that was readily converted into a 2-acetamido group by reduction. A segment of glycoprotein leukosialin (215-224) was synthesized by the solid-phase protocol, the building block (1b) being utilized. Cleavage of the synthetic glycopeptide from resin was effected with reagent K and subsequent treatment of the product with a cocktail for the ‘low-acidity TfOH’ facilitated complete removal of the benzyl groups with minimum loss of glycosidic linkages. To the deprotected glycopeptide (21), were enzymatically introduced N-acetylneuraminic acid (sialic acid) residues in remarkably high efficiency by using the specific sialyltransferases.