Anodic oxidation of p-But-calix[4]arene-(OH)2-(OCH2CONEt2)2. Electrogeneration of a calixdiquinone in dichloromethane

The electrochemical oxidation of p-Bu^t-calix[4]arene-(OH)₂-(OCH₂CONEt₂)₂ 1 has been investigated for the first time and was shown to result in the formation of the corresponding diquinone 3. The reaction proceeds via two successive two-electron irreversible oxidation steps both governed by an ECE mechanism. Alkali cations recognition can be realized by exhaustive oxidation of 1 in the presence of alkali salts.     

Synthesis of mono- and dihydroxy-substituted 2-aminocyclooctanecarboxylic acid enantiomers

(1R,2S,6R)-2-Amino-6-hydroxycyclooctanecarboxylic acid (?)-10 was synthesized from (1R,2S)-2-aminocyclooct-5-enecarboxylic acid (+)-2 via an iodolactone intermediate, while (1R,2S,3R,4S)-2-amino-5,6-dihydroxycyclooctanecarboxylic acid (?)-12 was prepared by using the OsO₄-catalyzed oxidation of Boc-protected amino ester (?)-5. The stereochemistry and relative configurations of the synthesized compounds were determined by 1D and 2D NMR spectroscopy (based on 2D NOE cross-peaks and ³J(H,H) coupling constants) and X-ray crystallography.     

Highly stereoselective synthesis of C2-chiral and meso nitroxides from an optically active pyrrolidine

Starting from (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine 1, hydroxylamine cis-3 was synthesized with high stereoselectivity by successive oxidation and addition of PhMgBr. By using PhLi, trans (C₂-chiral) pyrrolidine nitroxide trans-7 was obtained from nitrone 5 derived from hydroxylamine 3. The cis (meso) counterpart cis-7 was produced along with trans-7 when PhMgBr was employed in place of PhLi. Moreover, cis-7 was also obtained selectively by using PhLi and Et₂AlCl with nitrone 5. The change of stereochemical bias observed when EtMgBr and/or nitrone 10 bearing an ethyl group were employed is also discussed.     

Different oxidation pathways with various MnO2 types: Anomalous reaction with gibberellic acid

The oxidation of gibberellic acid (1) with neutral manganese dioxide prepared according to Mancera et al., involves the free carboxylic group and gives rise to three anomalous products which correspond to oxidative decarboxylation (3,4) or lactonization (5). Optimal conditions for a normal allylic oxidation of 1 have been found using alkaline MnO₂ prepared according to Attenburrow et al. in acetone which gives yields of keto acid (2) up to 56%.     

Reactivity and reaction pathways of alkylalkoxybenzene radical cations. Part 3. Effects of 2-alkyl substituents on the relative importance of ring-substitution over deprotonation of 2-alkyl-1,4-dimethoxybenzene radical cations

One-electron oxidation of 2-alkyl-1,4-dimethoxybenzenes 1a-f (2-alkyl=Me, Et, i-Pr, cy-C₃H₅CH₂, PhCH₂ and t-Bu) by 4-nitrobenzoyl peroxide 2 and pentaflurobenzoyl peroxide 3 was proved by the observation of great acceleration of decomposition of the peroxides at room temperature, the detection of the corresponding radical cations 1 ^+? a-f and product analysis. The product studies have disclosed that under the conditions employed (in acetonitrile at 40°C), the reaction pathways of the radical cations are greatly dependent on the nature of 2-alkyl substituents: Ring-4-nitrobenzoloxylation product at C ₅ and C ₆ were obtained exclusively in the reactions of the donors with aliphatic 2-alkyl substituents bearing at least one α-hydrogen atom, such as 1a, 1b, 1c and 1d; whereas in the case of 1e (with 2-benzyl group), both ring-substitution at C ₅ (4e) and C ₆ (5e) and deprotonation/4-nitrobenzoloxylation products 8e were isolated; from the donor without α-hydrogen atom, 1f, de-t-butylation products 12 and t-butyl 4-nitrobenzoate 13 were incorporated with ring-substitution at C ₅ (4f) and C ₆ (5f). Furthermore, the product distribution (4 over 5) is also affected by the bulkiness of 2-alkyl group. For all the electron-transfer reactions, large amounts of the benzoic acid (4-NO₂-C₆H₄COOH or C₆F₅COOH) were generated and trace amounts of de-methylation product (2-alkyl-1,4-benzoqinones 6) were also detected by ¹H NMR.     

Chemoenzymatic synthesis of enantiopure geminally dimethylated cyclopropane-based C2- and pseudo-C2-symmetric diamines

Enantiopure (−)-(1S,3S)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxamide 2 and (+)-(1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylic acid 3 were easily obtained from a multigram scale biotransformation of racemic amide or nitrile in the presence of Rhodococcus erythropolis AJ270 whole cell catalyst under very mild conditions. Coupled with efficient and convenient chemical manipulations, comprising mainly of the Curtius rearrangement, oxidation, and reduction reactions, chiral C₂-symmetric (1S,2S)-3,3-dimethylcyclopropane-1,2-diamine 6 and ((1R,3R)-3-(aminomethyl)-2,2-dimethylcyclopropyl)methanamine 8 and pseudo-C₂-symmetric (1S,3S)-3-(aminomethyl)-2,2-dimethylcyclopropanamine 11 were prepared. These were also transformed into the corresponding chiral salen derivatives 12, 13, and 14, respectively, in almost quantitative yields.     

Determination of absolute configuration using vibrational circular dichroism spectroscopy: the chiral sulfoxide 1-thiochroman S-oxide

We have determined the absolute configuration of the chiral sulfoxide 1-thiochroman S-oxide 1 using vibrational circular dichroism (VCD) spectroscopy. The VCD spectrum of a CCl₄ solution of 1 was analyzed using density functional theory (DFT), which predicts three stable conformations of 1, separated by <1 kcal/mol. The VCD spectrum predicted using the DFT/GIAO methodology for the equilibrium mixture of the three conformations of (S)-1 is in excellent agreement with the experimental spectrum of (+)-1. The absolute configuration of 1 is therefore (R)-(−)/(S)-(+). (+)-1 and (−)-1 of high enantiomeric excess (e.e.) were synthesized in high yields via asymmetric oxidation of 1-thiochroman 2 using Ti(iso-PrO)₄/(R,R)-1,2-diphenylethane-1,2-diol/H₂O/tert-butyl hydroperoxide and Ti(iso-PrO)₄/l-diethyl tartrate/H₂O/cumene hydroperoxide, respectively.     

Oxidative rearrangement of 2-alkoxy-3,4-dihydro-2H-pyrans: stereocontrolled synthesis of 4,5-cis-disubstituted tetrahydrofuranones including whisky and cognac lactones and crobarbatic acid

Oxidation of 2-alkoxy-3,4-dihydro-2H-pyrans 3 with dimethyldioxirane or MTO/urea-H₂O₂ followed by Jones oxidation leads to rearrangement and stereocontrolled formation of 4,5-cis-disubstituted tetrahydrofuranones. The method is applied to the synthesis of the whisky lactone 9, cognac lactone 10 and crobarbatic acid 17.     

Enantiopure erythro- and threo-1-aryl-1-[2-pyrrolidyl]-methanols: synthesis from l-proline

Enantiopure (1R,2S)-erythro- and (1S,2S)-threo-isomers of four new aryl-pyrrolidyl alcohols 5aH, 5aMe, 5bH and 5bMe have been obtained in five steps from (−)-(S)-proline and fully characterized. The oxidation of alcohol 8 into aldehyde 9 was the most difficult step and racemization occurs during Swern oxidation but this difficulty can be overcome by using SO₃/pyridine as oxidant. Diastereomer I of the protected amino alcohol 10a crystallized and was shown to be the (1R,2S)-erythro-isomer (e-10a-I) using X-ray crystallography. Therefore the (1R,2S)-erythro structure was assigned to all compounds obtained from e-10a-I, and, as a consequence, the (1S,2S)-threo structure was assigned to diastereomers II.     

Catalytic activity of CuI/CuII cyanide based phenanthroline-bicarbonate system for enhancing aerobic oxidation of 2,6-di-tert-butylphenol

The metal organic framework {[Cu₂(CN)₃(phen)₃]5H₂O} MOF1- bicarbonate system was investigated as an efficient catalyst for aerobic oxidation of 2, 6-di-tert-butylphenol (2,6- DTBP). The catalytic system showed very efficient catalytic behavior for the oxidation of selective coupling of 2,6- DTBP to 3,3′,5,5′-tetra-tert-butyl-4,4′-diphenoquinone (DPQ) in excellent yield. The influence of reaction parameters on the selective oxidation of 2, 6-DTBP to DPQ had been investigated. Photoluminescence probing technology of Disodium salt of terephthalic acid as well as scavenging experiments revealed the creation of the hydroxyl radicals as the main active oxidation radicals produced by the MOF1/O₂/basic bicarbonate system. The oxidation reaction mechanism was also discussed. The recycled catalytic system retained its activity for eight successive runs.     

Reactions of nitrosoarenes containing electron-withdrawing substituents with coordinated CO. Synthesis and structure of complexes Pd2(OAc)2(p-ClC6H4N[p-ClC6H3NO])2 and Pd2(OAc)2(o-ClC6H4N[o-ClC6H3NO])2

The reaction of tetranuclear Pd₄(μ-COOCH₃)₄(μ-CO)₄ cluster (1a) with p- and o-chloronitrosobenzenes was found to give dinuclear nitrosoamide complexes, Pd₂(OAc)₂(p-ClC₆H₄N[p-ClC₆H₃NO])₂ (4) and Pd₂(OAc)₂(o-ClC₆H₄N[o-ClC₆H₃NO])₂ (5), respectively. The formation of complexes 4 and 5 is accompanied by evolution of CO₂, resulting from oxidation of CO coordinated in cluster 1. Complexes 4 and 5 were characterized by elemental analysis and IR and ¹H NMR spectroscopy; their structures were studied by EXAFS. The reactions of dinuclear complex 4 with molecular hydrogen and CO were studied. The major products of reduction of 4 with hydrogen include metallic palladium, acetic acid, cyclohexanone, and molecular nitrogen. Treatment of complex 4 with CO under mild conditions (1 atm, 20 °C) affords p-chlorophenyl isocyanate.     

Kinetics and mechanism of oxidation of dimethyl sulfide with molecular oxygen catalysed by K[RuIII(EDTA-H)Cl] complex in water-dioxan medium

Oxidation of dimethyl sulfide (Me₂S) with molecular oxygen catalysed by [Ru^III(EDTA)(H₂O)]⁻1a (EDTA = ethylenediaminetetraacetate anion) was studied spectrophotometrically in water-dioxan medium at constant pH 5.0 (acetic acid-acetate buffer) and ionic strength 0.2 M (KCl). The reaction proceeds through the formation of a [Ru^III(EDTA)(Me₂S)]⁻2 intermediate which undergoes oxidation with molecular oxygen to give dimethyl sulfoxide (Me₂SO) as the oxidation product. The rate of formation of 2 and its decomposition was followed spectrophotometrically by monitoring the reactions at 528 nm the characteristic peak of 2. The rate of formation of 2 was found to be first order in the concentrations of 1a and Me₂S. The rate of decomposition of 2 is independent of the concentration of Me₂S and is half-order with respect to oxygen concentration. Both the formation and decomposition reactions of 2 were studied at different temperatures, and the activation parameters ΔH≠ and ΔS≠ were determined. A suitable mechanism was proposed for the catalytic oxidation of dimethyl sulfide to dimethyl sulfoxide with molecular oxygen.     

An efficient and stereospecific synthesis of (2S,4S)-2,4-diaminoglutaric acid

An efficient and stereospecific synthesis of (2S,4S)-2,4-diaminoglutaric acid 1 starting from trans-4-hydroxy-l-proline 2 is presented. The key step involves the combined application of ruthenium tetroxide (RuO₄) oxidation of 4-(tert-butoxycarbonylamino)proline derivatives 7 and 8 followed by regioselective ring opening of the resulting lactams 9 and 10 with 1 M LiOH.     

Syntheses and biological evaluation of BE-43547A2 analogues modified at O35 ester and C15-OH sites

Total syntheses of 6 BE-43547A₂ analogues modified at O35 and C15 sites are reported. Late stage oxidation of 15-deoxy-BE-43547A₂ delivered 15-epi-BE-43547A₂, which verified the proposition that the C15 is an active site for late stage oxidation. The N35 and C15-F of analogues 1b and 1d were synthesized. Cellular level tests indicated O35 is a prohibitive site for modification and substitution of the OH at C15 with F or trim of the OH both led to a dramatic loss of activity. Compound 1e showed comparable inhibitory level towards Panc-1?cells, which indicated that the OH at C15 are permissive site for further modifications.     

Efficient synthesis of 3,4- and 4,5-dihydroxy-2-amino-cyclohexanecarboxylic acid enantiomers

An efficient method for the synthesis of (1S,2R,4R,5S)- and (1R,2R,4R,5S)-2-amino-4,5-dihydroxycyclohexanecarboxylic acids (?)-6 and (?)-9 and (1R,2R,3S,4R)- and (1S,2R,3S,4R)-2-amino-3,4-dihydroxycyclohexanecarboxylic acids (?)-15 and (?)-18 was developed by using the OsO₄-catalyzed oxidation of Boc-protected (1S,2R)-2-aminocyclohex-4-enecarboxylic acid (+)-2 and (1R,2S)-2-aminocyclohex-3-enecarboxylic acid (+)-11. Good yields were obtained. The stereochemistry of the synthesized compounds was proven by NMR spectroscopy.     

Total synthesis of resolvin E2

Resolvin E2 (2) was synthesized stereoselectively using the C1-8 and C15-20 aldehydes 6 and 9, which were connected to the C9-14 fragment by using Wittig reactions. The aldehyde 6 was prepared from the γ-silyl alcohol (S)-20 by a sequence of reactions involving ozonolysis, oxidation with NaIO₄, and the Wittig reaction of the resulting aldehyde with Ph₃PCHCHO, whereas the aldehyde 9 was synthesized from the corresponding γ-silyl alcohol through epoxidation, reaction with Et₂AlCN, and reduction with DIBAL-H.     

Reversal of enantioselectivity on protonation of enol(ate)s derived from 2-methyl-1-tetralone using C2-symmetric sulfonamides

The synthesis of enantiomerically enriched (R)-2-methyl-1-tetralone 1 (64% e.e.) was achieved through protonation of its lithium enolate 3 using a C₂-symmetrical bis-sulfonamide 5d as an internal proton source. Access to the complementary (S)-enantiomer 1 (45% e.e.) can be achieved using an external quench strategy involving acetic acid as the external proton source.     

Hexacoordinate triphenylantimony(V) complex with tridentate bis-(3,5-di-tert-butyl-phenolate-2-yl)-amine ligand: Synthesis,NMR and X-ray study

The oxidative addition reaction of 4,6-di-tert-butyl-N-(2-hydroxy-3,5-di-tert-butyl-phenyl)-o-iminobenzoquinone (IBQ) to triphenylantimony(III) proceeds with the migration of hydroxyl-proton to a nitrogen atom to form tridentate O,N,O′-coordinated bis-(3,5-di-tert-butyl-phenolate-2-yl)-amine ligand. In accordance with ¹H, ¹³C, DEPT NMR data, the new hexacoordinate complex [bis-(3,5-di-tert-butyl-phenolate-2-yl)-amine]triphenylantimony(V), [(AP-AP)H]SbPh₃ (1) in solution has a C_s symmetry plane leading to the equivalence of two O,N-chelate o-aminophenolato moieties. The molecular structure of 1 · acetone was studied by a single-crystal X-ray. Compound 1 was found to be air-stable both in solid and in solution. Its oxidation by PbO₂ leads to paramagnetic [4,6-di-tert-butyl-N-(3,5-di-tert-butyl-phenolate-2-yl)-o-iminobenzosemiquinolato]triphenylantimony(V), [(AP-ISQ)]SbPh₃ (2).     

Heterodisubstituted 1,10-dicarba-closo-decaboranes from substituted nido-carborane precursors

Mono- and heterodisubstituted 1,10-dicarba-closo-decaboranes 1 have been prepared from substituted nido-carboranes 3 and by carboxylation and arylation of 1-alkyl-p-carboranes. Thermal dehydrogenation followed by skeletal rearrangement of 3 furnished 1 in modest yields. Alkyl substituents tolerated the high temperature process whereas the 4-bromophenyl derivative 1d underwent partial disproportionation. The preparation of the nido-carboranes 3 was accomplished in three ways: by acetylene insertion to nonaborane 6, modified Plešek oxidation of dicarbaundecaborate anions 4 with Fe(III), and a new homogenous oxidation of 4 using gaseous SO₂. The newly developed homogenous deboronation with SO₂ appears to be more efficient than the classical Plešek oxidation especially for highly lypophilic carboranes. The overall yields for the preparation of substituted p-carboranes 1 using the three methods from 6 or 4 are about 8% and 14%, respectively.     

Charge density studies on [(NO)Fe(S2C6H4)2][PPN] and [(NO)3Fe(S2C6H4)3] complexes

Charge density studies of chemical bonds for two iron complexes, [(NO)Fe(S,S-C₆H₄)₂] [PPN] (1), where PPN = N(Pph₃)₂ and Fe₃(NO)₃(S,S-C₆H₄)₃ (2) are investigated in terms of the topological properties at bond critical points based on the ‘atoms in molecule’ theory. The one electron reduction form (1R) of complex 1 and the one electron oxidation form (2O) of complex 2 are also included for comparison. The X-ray absorption spectroscopy of Fe K- and L_III,II-edges, as well as the N/S K-edge are applied to verify the illustration in the variation of the electronic structures. Based on the ρ_c, ?²ρ_c, and H_b values among the compound studied, Fe-S/N can be regarded as polarized covalent bond, and Fe-N bonds show stronger covalent character than that of the Fe–S bond, which is believed to be a highly polarized covalent bond.