RESUMO
Bicyclo[1.1.0]butane-containing compounds feature a unique chemical reactivity, trigger "strain-release" reaction cascades, and provide novel scaffolds with considerable utility in the drug discovery field. We report the synthesis of new bicyclo[1.1.0]butane-linked heterocycles by a nucleophilic addition of bicyclo[1.1.0]butyl anions to 8-isocyanatoquinoline, or, alternatively, iminium cations derived from quinolines and pyridines. The resulting bicyclo[1.1.0]butanes are converted with high regioselectivity to unprecedented bridged heterocycles in a rhodium(I)-catalyzed annulative rearrangement. The addition/rearrangement process tolerates a surprisingly large range of functional groups. Subsequent chemo- and stereoselective synthetic transformations of urea, alkene, cyclopropane, and aniline moieties of the 1-methylene-5-azacyclopropa[cd]indene scaffolds provide several additional new heterocyclic building blocks. X-ray structure-validated quantum mechanical DFT calculations of the reaction pathway indicate the intermediacy of rhodium carbenoid and metallocyclobutane species.
RESUMO
Monohydroboration of substituted 1,3-diynes with an N-heterocyclic carbene borane (NHC-borane) occurs under radical conditions using an azo initiator, such as ACCN and AIBN, and a thiol as a polarity-reversal catalyst. The reaction is highly regio- and stereoselective and provides stable NHC-(E)-alkynylalkenylboranes.
RESUMO
Polyfluoroarenes work as good radical acceptors in the thermal radical reaction with N-heterocyclic carbene boranes (NHC-boranes) in the presence of di-tert-butyl peroxide. In this reaction, a C-F bond of polyfluoroarenes is substituted with an NHC-boryl group to provide B-aryl NHC-borane derivatives. The developed synthetic method was applied to the synthesis of novel borane-containing liquid crystalline molecules having highly thermal stability.
RESUMO
Reactions of N-heterocyclic carbene boranes (NHC-boranes) with electron-poor aromatic rings under photoredox conditions provide dearomatized 3-NHC-boryl-1,5-cycohexadienes, which are formally products of 1,4-hydroboration reactions. When regioisomers are possible, the more crowded (doubly ortho-substituted) product is formed preferably or exclusively. The mechanism may involve oxidation of the NHC-borane to an NHC-boryl radical, reduction of the electron-poor aromatic ring to a radical anion, coupling of the radical and the radical anion to give a cyclohexadienyl anion, and finally regioselective protonation.
RESUMO
An N-heterocyclic-carbene-ligated 3-benzoborepin with a bridged structure has been synthesized by double radical trans-hydroboration of benzo[3,4]cycloundec-3-ene-1,5-diyne with an N-heterocyclic carbene borane. The thermal reaction of the NHC-ligated borepin at 150 °C gives an isolable NHC-boranorcaradiene. Experiments and density functional theory calculations support a mechanism whereby the borepin initially rearranges to a boranorcaradiene by a thermal 6π-electrocyclic reaction. This is followed by 1,5-boron shift to give a rearranged boranorcaradiene. This shift occurs with stereoinversion at boron through a transition state with open-shell diradical character. This is the first example of the isolation of a boranorcaradiene from a thermal reaction of a borepin.
RESUMO
Reactions of readily available alkenyl triflates with N-heterocyclic carbene (NHC)-boranes in the presence of diisopropyl ethyl amine provided about three dozen stable α-NHC-boryl ketones. Isolated yields were typically 40-56% for B-unsubstituted NHC-boranes (NHC-BH3), and somewhat lower for NHC-boranes with B-substituents (NHC-BH2R). The requisite alkenyl triflates can be made separately or prepared in situ from either ketones or alkynes. The experimental evidence supports a radical chain mechanism that involves the following: (1) addition of an NHC-boryl radical to the alkenyl triflate, (2) fragmentation to give the α-NHC-boryl ketone, SO2, and trifluoromethyl radical, and (3) hydrogen abstraction by trifluoromethyl radical from the starting NHC-borane to return the NHC-boryl radical along with trifluoromethane. Reactions 1 and 3 are both new and evidently rather fast.
RESUMO
Substituted propargyl acetates are converted into 4-boryl-2(5H)-furanones upon thermolysis in the presence of an N-heterocyclic carbene borane (NHC-borane) and di-tert-butyl peroxide. The acetyl methyl group is lost during the reaction as methane. Evidence suggests that the reaction proceeds by a sequence of radical events including: 1)â addition of an NHC-boryl radical to the triple bond; 2)â cyclization of the resultant ß-borylalkenyl radical to the ester carbonyl group; 3)â ß-scission of the so-formed alkoxy radical to provide the 4-boryl-2(5H)-furanone and a methyl radical; and 4)â hydrogen abstraction from the NHC-borane to return the initial NHC-boryl radical and methane.
RESUMO
The first ring-opening reactions of ligated boriranes (boracyclopropanes) are described. Treatment of readily available NHC-boriranes bearing ester substituents on the borirane ring with HCl provides stable γ-NHC-bora-γ-lactones in isolated yields ranging from 40% to 73%. The reactions occur through 1,3-addition of HCl across a B-C bond of the NHC-borirane to form a ring-opened NHC-boryl chloride, followed by lactonization with chloride displacement. Experimental evidence suggests that both the borirane ring-opening reaction and the boralactonization reaction occur with inversion at boron.
RESUMO
N-Heterocyclic carbene boranes (NHC-boranes) react with 5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dione at 40 °C in dichloromethane to provide NHC-boryl hydrazone derivatives of 2,2-dimethyl-1,3-dioxane-4,6-dione. These hydrazones disproportionate to bis-hydrazones on treatment with diiodine in dichloromethane at room temperature. The mono- and bis-hydrazones are yellow solids that are stable to chromatography and storage.
RESUMO
Basic hydrolyses of various ligated α-boryl acetic acid esters provided the first ligated derivatives of the unknown compound boroacetic acid (BH2 CH2 CO2 H). Four monoacids (L-BH2 CH2 CO2 H) and one diacid (L-BH(CH2 CO2 H)2 ) were prepared with N-heterocyclic carbene, amine, and pyridine ligands (L). The stable acids were characterized by X-ray crystallography and acidity constant (pKa ) measurements. They rank among the least acidic of all known carboxylic acids. In turn, their conjugate bases are among the strongest of all carboxylates.
RESUMO
Thermal reactions of benzo[3,4]cyclodec-3-ene-1,5-diyne with N-heterocyclic carbene boranes (NHC-boranes) provided mixtures of 9-borylated 1,2,3,4-tetrahydroanthracenes along with 1,2,3,4-tetrahydroanthracene. These products indicate that NHC-boranes serve as hydrogen donors to a p-benzyne intermediate formed by the Masamune-Bergman reaction. Experimental results support a radical mechanism in nonpolar solvents, but suggest that ionic mechanisms compete in the production of 1,2,3,4-tetrahydroanthracene when the reaction is performed in a polar solvent.
RESUMO
The Rh(I)-catalyzed allenic Pauson-Khand reaction (APKR) is an efficient, redox-neutral method of synthesizing α-acyloxy cyclopentenones. An enantioselective APKR could provide access to chiral, nonracemic α-acyloxy and α-hydroxy cyclopentenones and their corresponding redox derivatives, such as thapsigargin, a cytotoxic natural product with potent antitumor activity. Rapid scrambling of axial chirality of allenyl acetates in the presence of Rh(I) catalysts enables the conversion of racemic allene to enantiopure cyclopentenone product in a dynamic kinetic asymmetric transformation (DyKAT). A combined experimental and computational approach was taken to develop an effective catalytic system to achieve the asymmetric transformation. The optimization of the denticity, and steric and electronic properties of the ancillary ligand (initially (S)-MonoPhos, 58:42 er), afforded a hemilabile bidentate (S)-MonoPhos-alkene-Rh(I) catalyst that provided α-acyloxy cyclopentenone product in up to 14:86 er. Enantioselectivity of the Rh(I)-(S)-MonoPhos-alkene catalyst was rationalized using ligand-substrate steric interactions and distortion energies in the computed transition states. This asymmetric APKR of allenyl acetates is a rare example of a Type I DyKAT reaction of an allene, the first example of DyKAT in a cyclocarbonylation reaction, and the first catalyst-controlled enantioselective APKR.
Assuntos
Acetatos/química , Ciclopentanos/síntese química , Acetatos/síntese química , Alcenos/química , Catálise , Ciclopentanos/química , Cinética , Ligantes , Reprodutibilidade dos Testes , Rodaminas/química , Estereoisomerismo , Tapsigargina/síntese química , Tapsigargina/químicaRESUMO
Boron-hydrogen bond insertion reactions of N-heterocyclic carbene (NHC) boranes and diazoesters can be catalyzed by NHC-boryl iodides and produce stable α-NHC-boryl esters. The conditions of the reaction resemble the previous rhodium-catalyzed transformations (only the catalyst is different); however, the mechanisms of the two reactions are probably very different. The new boryl iodide catalyzed method is adept at producing α-substituted-α-NHC-boryl esters, and this has led to a family of NHC-boryl esters with amino acid and amino-acid-like side chains.
RESUMO
Reaction of bis-(2,6-diisopropylphenyl)-imidazol-2-ylidene borane with dimethyl acetylenedicarboxylate gives 80% yield of a stable borirane (boracyclopropane) formed by formal double hydroboration along with 5% of the (E)-alkenylborane. DFT calculations suggest a mechanism where divergence to the two products occurs after a common initial stage of hydride transfer from the NHC-borane to the acetylenedicarboxylate.
RESUMO
The phosphatase PTP4A3 is an attractive anticancer target, but knowledge of its exact role in cells remains incomplete. A potent, structurally novel inhibitor of the PTP4A family was obtained by photooxygenation of a less active, electron-rich thienopyridone (1). Iminothienopyridinedione 13 displays increased solution stability and is readily obtained by two new synthetic routes that converge in the preparation of 1. The late-stage photooxygenation of 1 to give 13 in high yield highlights the potential of this reaction to modify the structure and properties of a biological lead compound and generate value for expanding the scope of an SAR investigation. Analog 13 should become a valuable tool for further exploration of the role of PTP4A3 in tumor progression.
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Oxigênio/química , Processos Fotoquímicos , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Piridonas/química , Piridonas/farmacologiaRESUMO
We identified vibrational spectral marker bands that sensitively report on the side chain structures of glutamine (Gln) and asparagine (Asn). Density functional theory (DFT) calculations indicate that the Amide III(P) (AmIII(P)) vibrations of Gln and Asn depend cosinusoidally on their side chain OCCC dihedral angles (the χ3 and χ2 angles of Gln and Asn, respectively). We use UV resonance Raman (UVRR) and visible Raman spectroscopy to experimentally correlate the AmIII(P) Raman band frequency to the primary amide OCCC dihedral angle. The AmIII(P) structural sensitivity derives from the Gln (Asn) Cß-Cγ (Cα-Cß) stretching component of the vibration. The Cß-Cγ (Cα-Cß) bond length inversely correlates with the AmIII(P) band frequency. As the Cß-Cγ (Cα-Cß) bond length decreases, its stretching force constant increases, which results in an upshift in the AmIII(P) frequency. The Cß-Cγ (Cα-Cß) bond length dependence on the χ3 (χ2) dihedral angle results from hyperconjugation between the CδâOϵ (CγâOδ) π* and Cß-Cγ (Cα-Cß) σ orbitals. Using a Protein Data Bank library, we show that the χ3 and χ2 dihedral angles of Gln and Asn depend on the peptide backbone Ramachandran angles. We demonstrate that the inhomogeneously broadened AmIII(P) band line shapes can be used to calculate the χ3 and χ2 angle distributions of peptides. The spectral correlations determined in this study enable important new insights into protein structure in solution, and in Gln- and Asn-rich amyloid-like fibrils and prions.
Assuntos
Asparagina/química , Glutamina/química , Óxido de Deutério/química , Estrutura Molecular , Análise Espectral Raman/métodos , Água/químicaRESUMO
The observation that NHC-boryl radicals abstract cyano groups from various organic nitriles has been parlayed into two complementary transformations. In the main group chemistry aspect, reactions of various NHC-boranes with simple organic dinitriles selectively provide stable NHC-boryl mono- or dinitriles, depending on the nitrile source. In the organic synthesis aspect, reaction of malononitriles and related derivatives with readily available 1,3-dimethylimidazol-2-ylidene borane provides reductively decyanated products in good yields.
RESUMO
We investigated the normal mode composition and the aqueous solvation dependence of the primary amide vibrations of propanamide. Infrared, normal Raman, and UV resonance Raman (UVRR) spectroscopy were applied in conjunction with density functional theory (DFT) to assign the vibrations of crystalline propanamide. We examined the aqueous solvation dependence of the primary amide UVRR bands by measuring spectra in different acetonitrile/water mixtures. As previously observed in the UVRR spectra of N-methylacetamide, all of the resonance enhanced primary amide bands, except for the Amide I (AmI), show increased UVRR cross sections as the solvent becomes water-rich. These spectral trends are rationalized by a model wherein the hydrogen bonding and the high dielectric constant of water stabilizes the ground state dipolar (-)O-CâNH2(+) resonance structure over the neutral OâC-NH2 resonance structure. Thus, vibrations with large C-N stretching show increased UVRR cross sections because the C-N displacement between the electronic ground and excited state increases along the C-N bond. In contrast, vibrations dominated by CâO stretching, such as the AmI, show a decreased displacement between the electronic ground and excited state, which result in a decreased UVRR cross section upon aqueous solvation. The UVRR primary amide vibrations can be used as sensitive spectroscopic markers to study the local dielectric constant and hydrogen bonding environments of the primary amide side chains of glutamine (Gln) and asparagine (Asn).
Assuntos
Amidas/química , Asparagina/química , Glutamina/química , Ligação de Hidrogênio , Teoria Quântica , Análise Espectral Raman , Vibração , Água/químicaRESUMO
The direct addition of anionic secondary phosphine boranes to carbodiimides yields both chiral and achiral phosphaguanidine boranes under ambient temperature conditions. An analogous preparation of menthol-derived phosphinite boranes is also described. These products can be deborinated to give the corresponding phosphines, and subsequently oxidized to give phosphine oxides. The robustness of this method was further demonstrated in the synthesis of structurally novel cyclic phosphaguanidines.