Hydroxyl-functionalized triazolylidene-based PEPPSI complexes: metallacycle formation effect on the Suzuki coupling reaction.

We report the preparation and full characterization of a series of hydroxyl functionalized 1,2,3-triazolylidene-based PEPPSI complexes 2a-c and their catalytic application in the Suzuki cross coupling reaction of aryl chlorides/amides with boronic acids. Under basic reaction conditions, complexes 2a-c show a notable increase in their catalytic efficiency compared with two ether-wingtip functionalized PEPPSI analogues (3 and 4) and a commercially available NHC-Pd complex (5). The catalytic results suggest that deprotonation of the hydroxyl group in complexes 2a-c plays an important role in the overall process. Deprotonation of the alcohol moiety of complexes 2a-b with sodium tert-butoxide allows for the isolation of metallacycles 6a-b, which are proposed as the active species of cross coupling reactions.

Evaluation of biocompatible monomers as substitutes for TEGDMA in resin-based dental composites.

This works reports the synthesis and characterization of diallyl(5-(hydroxymethyl)-1,3-phenylene) dicarbonate (HMFBA) and 5-(hydroxymethyl)-1,3-phenylene bis(2-methylacrylate) (HMFBM) monomers and its evaluation as Bis-GMA eluents in the formulation of composite resins for dental use. The experimental materials formulated with HMFBA and HMFBM monomers presented flexural strength values similar to those of the control group formulated with Bis-GMA/TEGDMA. Regarding volumetric contraction percentage, the values obtained of experimental materials with HMFBA was 1.88% and for HMFBM was 4.15%, both lower than control resin (4.68%). In the case of double bond conversion, the resin formulated with HMFBA monomer exhibited a greater degree of conversion (87%). Besides, the DMA analyses proved that the values for Tg guarantee a good mechanical performance at body temperature. The new resins formulated with HMFBA and HMFBM monomers exhibit a cellular viability close to 100%, which indicates the absence of cytotoxicity towards fibroblastic cells.

Expedient Synthesis of Highly Functionalized Abnormal Carbenegold(I) Complexes.

The reaction of 4-substituted imidazol-2-ylidenes with various electrophiles produces a series of 2,4-functionalized imidazolium salts. Subsequent metalation of these precursors using AuCl(SMe2) provides the first examples of highly functionalized abnormal carbenegold(I) complexes. The present protocol introduces a new strategy for the synthesis of metallic abnormal carbenes featuring diverse functional groups.

Bridged N-Heterocyclic/Mesoionic (NHC/MIC) Heterodicarbenes as Ligands for Transition Metal Complexes.

Following a copper catalyzed alkyne azide cycloaddition (CuAAC) and N-alkylation protocols, we report the preparation of a hybrid N-heterocyclic/mesoionic [NHC(H+)-MIC(H+)][2I]2- salt (1) in high yields. The treatment of salt 1 with Cu2O and KI yields a second hybrid NHC/MIC proligand featuring a tetraiodocuprate anion [NHC(H+)-MIC(H+)][Cu2I4]2- (2). Through selective deprotonation and metalation, both salts 1 and 2 can generate either the chelate heterodicarbene complexes (3) with the rare [NHC·(M)·MIC]+[MX2]- general formula (M = PdII, RhI) or NHC-anchored/pendent triazolium species (4) [NHC·(M)-MIC(H+)]. If the triazolium moiety of type 4 complexes is deprotonated with KHMDS in the presence of a second metal center, a series of heterobimetallic complexes of the type [NHC·(M)-MIC·(M')] (5) are achieved. Interestingly, the reaction of salt 2 with KHMDS yields the bimetallic copper heterodicarbene (6) which can be a useful transfer reagent for the preparation of type 3 complexes. A variety of synthetic routes for the preparation of complexes 3-5 and their full characterization in solution and in the solid state will be discussed.

Visible-Light-Promoted AuI to AuIII Oxidation in Triazol-5-ylidene Complexes.

Reaction of triazolium precursors [MIC(CH2 )n - H+ ]I- (n=1-3) with potassium hexamethyldisilazane (KHMDS) and AuCl(SMe2 ) generates the gold(I) complexes of the type MIC(CH2 )n ⋅AuI. Visible light exposure of the latter complexes promotes a spontaneous disproportionation process rendering gold(III) complexes of the type [{MIC(CH2 )n }2 ⋅AuI2 ]+ I- . Both the AuI and AuIII complex series were tested in the catalytic hydrohydrazination of terminal alkynes using hydrazine as nitrogen source.

Stereospecific (5) JHortho,OMe couplings in methoxyindoles, methoxycoumarins, and methoxyflavones.

Long-range coupling constants (5) JHortho,OMe were measured in series of methoxyindoles, methoxycoumarins, and methoxyflavones by the modified J doubling in the frequency domain method. The COSY and NOESY spectra revealed the coupling of the -OMe group with a specific proton at the ortho position and its preferred conformation. Homonuclear (1) H-(1) H couplings were confirmed by irradiation of the -OMe signal. Density functional theory calculations of (5) JHortho,OMe using the modified aug-cc-pVTZ basis set evidenced that the Fermi contact term shows good agreement with the experimental J values. Accurate chemical shift and coupling constant values followed after iterative quantum mechanical spectral analysis using the PERCH software.

Copper(II) complexes supported by click generated mixed NN, NO, and NS 1,2,3-triazole based ligands and their catalytic activity in azide-alkyne cycloaddition.

The preparation and characterization of four new copper(ii) complexes supported by click generated mixed NN, NO, and NS 1,2,3-triazoles are reported. The four complexes display a 1 : 2 copper/ligand ratio and give monomeric units in the solid state. Crystal structures demonstrate that depending on the flexibility of the ligand NX (X = O, N, S) pendant arm, the coordination environment around the metal center can feature square planar or octahedral geometries. All four complexes are catalytically active at room temperature in a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction using sodium ascorbate as a reducing agent and water-ethanol as a solvent mixture. Complex 8 supported by the NS ligand displayed the best catalytic performance of the series allowing for the easy and high yielding preparation of a variety of mono-, bis- and tris-1,2,3-triazoles under low catalyst loadings.

Preparation of O-methyl substituted 2-oxofuro- and 2-oxopyrrolidinoindolines by reductive lactonization of oxindol-3-ylacetic acids.

A practical procedure for the preparation of O-methyl substituted 3a,8-dialkyl-2-oxofuroindolines is described. Reductive lactonization of the corresponding oxindol-3-ylacetic acids provides a route for the formation of this class of compounds. Further transformation of 2-oxofuroindolines into 2-oxopyrrolidinoindolines, and then to pyrrolidinoindolines demonstrates their versatility as key intermediates in natural products synthesis. The results of single-crystal X-ray crystallographic analyses are given for five of the studied compounds.

C-6 regioselective bromination of methyl indolyl-3-acetate.

An efficient route to natural occurring methyl 6-bromoindolyl-3-acetate 1c from methyl indolyl-3-acetate 3 was achieved in 3 steps and 68% overall yield. Thus, in order to regioselectively brominate 3 at the C6-position, introduction of electron withdrawing substituents at N1 and C8 was affected to give intermediate 4 in 82% yield. Bromination of 4 with 8 equiv of bromine in CCl4 and washings with aqueous Na2SO3 gave 5 in 86% yield, which was N- and C-decarbomethoxylated by treatment with NaCN in DMSO, affording 1c in 97% yield. The regioselectivity of bromination was evidenced by NMR spectroscopy and X- ray diffraction analysis.

Unimolecular rearrangements of ketene-O,O-acetals and fragmentations occurring in the gas phase.

Gas phase skeletal rearrangements of regioisomeric 3-cyano-2-methoxy-3a-alkylfuro[2,3-b]- and [3,2-b]indoles were evidenced by product ions [M-32](+•), consistent with loss of methanol, on electron ionization in their mass spectra. The rearranged products occurring in gas phase were demonstrated to have elemental composition and fragmentation properties identical to those of authentic samples of 2-indolyl cyanomalonates. Isotopic labeling experiments support the formation mechanism of the [M-32](+•) ion. Additional thermal gas-phase reaction products were characterized by comparison with an authentic sample.

Cascade [1,3]-sigmatropic rearrangements of ketene O,O-acetals: kinetic and DFT level mechanistic studies.

The regioisomeric alpha-cyano ketene-O,O-dialkyl acetals 2a-e and 4a-e, sequential intermediates in the diazomethane induced conversion of indole alpha-cyano-gamma-lactones 1a-e to 2-indolyl cyanomalonates 5a-e, were isolated and characterized. Formation of the steady-state intermediate cycloprop[b]indoles 3a-e was evidenced by means of NMR and confirmed by the X-ray structure of 3c, demonstrating that the formation of 5a-e from 2a-e proceeds through two consecutive and one parallel unimolecular steps, with intermediates 3a-e formed in reversible processes. Evidence that the reversible reactions proceed via [1,3]-rearrangements is presented. The steady-state kinetic approach applied to intermediate 3 allowed a minimal two consecutive step 2 --> 4--> 5 kinetic model, in which the steric bulkiness of the alkyl substituent affects strongly the associated rate constants, k(1) and k(2), inverting the rate-determining step. The solvation effects enhanced the feasibility of these skeletal rearrangements as they stabilized the transition states to a great extent. The experimental determined thermodynamic parameters and DFT calculations suggest that these cascade rearrangements occur through [1,3]-sigmatropic mechanisms, in which asynchronous bond reorganization processes via four membered pseudopericyclic transition states are highly favorable.

DMD mediated formal synthesis of (+/-)-coerulescine.

A highly efficient method for the formal synthesis of the natural product (+/-)-coerulescine 1 from tetrahydro-beta-carboline 3, mediated by dimethyldioxirane (DMD), is described. Compound 15, the N9-demethylated precursor of 1, was prepared from 3 in 4 steps with an overall yield of 95%. The effect of electron withdrawing groups at the N2,N9 atoms of 3 was explored for the oxidative rearrangement step.

Synthesis of bromoindole alkaloids from Laurencia brongniartii.

A regioselective synthesis of N-carbomethoxy-2,3,5-tribromoindole (6) via a sequential one-pot bromination-aromatization-bromination of N-carbomethoxyindoline (2) is described. The process for the transformation of 2 into 6 permitted the isolation of stable reaction intermediates N-carbomethoxy-5-bromoindoline (3), N-carbomethoxy-5-bromoindole (4), and N-carbomethoxy-3,5-dibromoindole (5). Compound 6 was used to complete the total synthesis of the natural products 1b and 1c. In addition, bromination of N-carbomethoxyindole (11) afforded N-carbomethoxy-2,3,6-tribromoindole (13), from which the natural product 1a was synthesized.

Aromatic bromination versus oxidation of indolylmalonates by bromine.

The reactions of 5-substituted indolylmalonates (2a-e), carrying an electron-withdrawing group at the N(1) position, with bromine in CCl(4) or AcOH are reported. These substrates undergo oxidation in competition with the well-known aromatic bromination. Under the two sets of conditions, with parent indolylmalonate (2a), chemospecific oxidation is observed, whereas with 5-hydroxyindolylmalonate (2c), bromination at the 4- and 6-position is the dominating reaction. Investigation of the products composition of several 5-substituted indolylmalonates revealed the following trend: with a 5-substituted electron-withdrawing group like fluorine, the indolylmalonate undergoes oxidation rather than bromination. In contrast, with a 5-substituted electron-donating group, like a hydroxyl group, the ring bromination occurs preferentially over the oxidation. When the 5-substituent is an alkoxyl group, a significant amount of brominated-oxidized products is obtained. Monitoring the oxidation reaction by mass spectrometry allowed the characterization of the 2-bromoindolylidenemalonate intermediate. A bromonium ion is considered as possible pathway in the formation of this intermediate. The conformation of unsymmetrical methoxyl and benzyloxyl substituents was determined from (1)H NMR spectra, single-crystal X-ray diffraction and ab initio calculations.

Stereochemical assignment of naturally occurring 2,3-epoxy-2-methylbutanoate esters.

A method to determine the absolute configuration of 2,3-epoxy-2-methylbutanoate ester residues in natural products is presented, based on (i) the reduction of the ester function to yield a 2-methyl-1,2-butanediol, (ii) esterification of the obtained primary alcohol with either (R)-(+)- or (S)-(-)-Mosher's acid to afford the corresponding Mosher's ester, and (iii) 1H-NMR spectral comparison of the final product with that of the Mosher's esters prepared from 2-methyl-1,2-butanediols of known stereochemistry.