Showing papers on "Bicyclic molecule published in 2015"
TL;DR: The inexpensive, high-potential TEMPO derivative, 4-acetamido-TEMPO (ACT), exhibits higher electrocatalytic activity than AZADO and ABNO for the oxidation of primary and secondary alcohols.
Abstract: Bicyclic nitroxyl derivatives, such as 2-azaadamantane N-oxyl (AZADO) and 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO), have emerged as highly effective alternatives to TEMPO-based catalysts for selective oxidation reactions (TEMPO = 2,2,6,6-tetramethyl-1-piperidine N-oxyl). Their efficacy is widely attributed to their smaller steric profile; however, electrocatalysis studies described herein show that the catalytic activity of nitroxyls is more strongly affected by the nitroxyl/oxoammonium redox potential than by steric effects. The inexpensive, high-potential TEMPO derivative, 4-acetamido-TEMPO (ACT), exhibits higher electrocatalytic activity than AZADO and ABNO for the oxidation of primary and secondary alcohols. Mechanistic studies provide insights into the origin of these unexpected reactivity trends. The superior activity of ACT is especially noteworthy at high pH, where bicyclic nitroxyls are inhibited by formation of an oxoammonium hydroxide adduct.
180 citations
TL;DR: A new compound with the formula L-B2-L wherein the stabilizing ligand (L) is 1,3-bis[diisopropylphenyl]-4,5-dihydroimidazol-2-ylidene (SIDip) has been synthesized, isolated, and characterized.
Abstract: A new compound with the formula L-B2-L wherein the stabilizing ligand (L) is 1,3-bis[diisopropylphenyl]-4,5-dihydroimidazol-2-ylidene (SIDip) has been synthesized, isolated, and characterized. The π-acidity of the SIDip ligand, intermediate between the relatively non-acidic IDip (1,3-bis[diisopropylphenyl]imidazol-2-ylidene) ligand and the much more highly acidic CAAC (1-[2,6-diisopropylphenyl]-3,3,5,5-tetramethylpyrrolidin-2-ylidene) ligand, gives rise to a compound with spectroscopic, electrochemical, and structural properties between those of L-B2-L compounds stabilized by CAAC and IDip. Reactions of all three L-B2-L compounds with CO demonstrate the differences caused by their respective ligands, as the π-acidities of the CAAC and SIDip carbenes enabled the isolation of bis(boraketene) compounds (L(OC)B-B(CO)L), which could not be isolated from reactions with B2(IDip)2. However, only B2(IDip)2 and B2(SIDip)2 could be converted into bicyclic bis(boralactone) compounds.
101 citations
TL;DR: A rhodium-catalyzed (4+1) cyclization between cyclobutanones and allenes is described, which provides a distinct [4.2.1]-bicyclic skeleton containing two quaternary carbon centers.
Abstract: Herein we describe a rhodium-catalyzed (4+1) cyclization between cyclobutanones and allenes, which provides a distinct [4.2.1]-bicyclic skeleton containing two quaternary carbon centers. The reaction involves C–C activation of cyclobutanones and employs allenes as a one-carbon unit. A variety of functional groups can be tolerated, and a diverse range of polycyclic scaffolds can be accessed. Excellent enantioselectivity can be obtained, which is enabled by a TADDOL-derived phosphoramidite ligand. The bridged bicyclic products can be further functionalized or derivatized though simple transformations.
99 citations
TL;DR: In this article, the first chemo-and site-selective process for the formation of N-aryl-carbamates from cyclic organic carbonates and aromatic amines is reported.
Abstract: The first chemo- and site-selective process for the formation of N-aryl-carbamates from cyclic organic carbonates and aromatic amines is reported. The reactions proceed smoothly under extremely mild reaction conditions using TBD (triazabicyclodecene) as an effective and cheap organocatalyst, thus providing a sustainable and new methodology for the formation of a wide variety of useful N-aryl carbamate synthons in good to excellent yields. Computational investigations have been performed and show the underlying reason for the observed unique reactivity as related to an effective proton-relay mechanism mediated by the bicyclic guanidine base.
97 citations
TL;DR: The hemilabile chelate facilitates conversion of a principally ligand-based singly occupied molecular orbital (SOMO) in the cobalt dinitrogen and alkene compounds to a metal-based SOMO in the diene intermediates, promoting C–C bond-forming oxidative cyclization.
Abstract: Aryl-substituted bis(imino)pyridine cobalt dinitrogen compounds, (RPDI)CoN2, are effective precatalysts for the intramolecular [2π + 2π] cycloaddition of α,ω-dienes to yield the corresponding bicyclo[3.2.0]heptane derivatives. The reactions proceed under mild thermal conditions with unactivated alkenes, tolerating both amine and ether functional groups. The overall second order rate law for the reaction, first order with respect to both the cobalt precatalyst and the substrate, in combination with electron paramagnetic resonance (EPR) spectroscopic studies established the catalyst resting state as dependent on the identity of the precatalyst and diene substrate. Planar S = 1/2 κ3-bis(imino)pyridine cobalt alkene and tetrahedral κ2-bis(imino)pyridine cobalt diene complexes were observed by EPR spectroscopy and in the latter case structurally characterized. The hemilabile chelate facilitates conversion of a principally ligand-based singly occupied molecular orbital (SOMO) in the cobalt dinitrogen and alkene...
74 citations
TL;DR: A type II intramolecular oxidopyrylium-mediated [5+2] cycloaddition reaction allows the efficient and diastereoselective formation of various highly functionalized and synthetically challenging bridged seven-membered ring systems.
Abstract: A type II intramolecular oxidopyrylium-mediated [5+2] cycloaddition reaction allows the efficient and diastereoselective formation of various highly functionalized and synthetically challenging bridged seven-membered ring systems (such as bicyclo[4.4.1]undecane, bicyclo[4.3.1]decane, bicyclo[5.4.1]dodecane, and bicyclo[6.4.1]]tridecane). This simple, thermal, direct transformation has a broad substrate scope and is high yielding, with high functional-group tolerance and unique endo selectivity. The highly strained tricyclic cores of ingenol mebutate (picato) and cyclocitrinol are synthesized efficiently and diastereoselectively using this methodology.
62 citations
TL;DR: The calculated theoretical rate expression for each reaction, as a result of the mechanism elucidated with density functional theory calculations, agrees well with the respective experimentally observed rate equation.
Abstract: Chiral bicyclic guanidine can act as an efficient chiral Bronsted base catalyst in enantioselective reactions, delivering good yields with high enantioselectivities. There is interest in understanding the detailed mechanisms of these guanidine-catalyzed reactions. Herein, we performed a detailed kinetic study of three different types of chiral bicyclic guanidine-catalyzed reactions, determining the bifunctionality of our guanidine catalyst. Although these three reactions share a similar catalytic cycle, their intrinsic kinetic behaviors are significantly different from each other because of the difference in the rate-determining step. The calculated theoretical rate expression for each reaction, as a result of the mechanism elucidated with density functional theory calculations, agrees well with the respective experimentally observed rate equation.
61 citations
TL;DR: Based on this methodology, divergent total syntheses of atisane-type diterpenoids, including (±)-crotobarin, crotogoudin, at isane-3β,16α-diol, and 16S,17-dihydroxy-atisan-3-one, were accomplished in 14, 14, 12, and16 steps, respectively.
Abstract: Few examples of [4 + 2] cycloaddition with unmasked ortho-benzoquinones (UMOBs) as carbodiene have been reported in complex molecule synthesis. Herein we report that this cycloaddition with podocarpane-type UMOB was developed and applied to construct fully functionalized bicyclo[2.2.2]octanes. Based on this methodology, divergent total syntheses of atisane-type diterpenoids, including (±)-crotobarin, crotogoudin, atisane-3β,16α-diol, and 16S,17-dihydroxy-atisan-3-one, were accomplished in 14, 14, 12, and 16 steps, respectively. Key elements in these total syntheses include: (1) FeCl3-catalyzed cationic cascade cyclization to construct podocarpane-type skeleton; (2) Mn(III)/Co(II)-catalyzed radical hydroxylation of alkene with high regio-, diastereo-, and chemoselectivities; (3) and a ketal-deprotection/lactone-opening/deprotonation/lactonization cascade. Additionally, the synthetic utility of the fully functionalized bicyclo[2.2.2]octane framework was further elucidated by applying ring distortion strateg...
60 citations
TL;DR: Calculations revealed that stepwise C–C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst.
Abstract: A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83-99% ee) and in good yields (60-90%). Calculations revealed that stepwise C-C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst.
60 citations
TL;DR: Highly enantioselective copper(I)-catalyzed hydroboration of bicyclic alkenes is reported using a copper-taniaphos complex and methods with the same chiral ligand-copper precursors were developed using different boron sources based on alternative mechanistic pathways.
56 citations
TL;DR: The N-heterocyclic carbene-catalyzed cascade reaction of enals with malonates to give bicyclic δ-lactones was developed and obtained in high yields with excellent diastereo- and high enantioselectivities.
TL;DR: An unprecedented formal hydroallylation of the bicyclic alkenes is realized in high efficiency by using an inexpensive cobalt salt as the catalyst and easy-to-handle potassium allyltrifluoroborate as the reagent.
Abstract: The allylation of heterobicyclic alkenes is presented for the first time. By using an inexpensive cobalt salt as the catalyst and easy-to-handle potassium allyltrifluoroborate as the reagent, an unprecedented formal hydroallylation of the bicyclic alkenes is realized in high efficiency. When a chiral cobalt/bis(phosphine) complex is used instead, the alternative ring-opening products can be obtained in high yield and excellent enantioselectivity.
TL;DR: With this method, a variety of unique substituted chiral fused bicyclic azepines, bearing multiple contiguous stereogenic centers, were facilely accessed in a straightforward, high-yielding, and highly stereoselective manner under mild reaction conditions.
Abstract: The first rhodium-catalyzed intramolecular hetero-[5+2] cycloaddition reaction of vinyl aziridines and alkenes was realized, wherein both internal and terminal alkenes were applicable. With this method, a variety of unique substituted chiral fused bicyclic azepines, bearing multiple contiguous stereogenic centers, were facilely accessed in a straightforward, high-yielding, and highly stereoselective manner under mild reaction conditions. Notably, the E/Z geometry of the CC bonds in the vinyl aziridine-alkene substrates impact the cis/trans stereochemistry of the cycloadducts and up to six stereoisomers could be delivered.
TL;DR: A new type of intramolecular carbene cascade reaction of alkynyl-tethered styryl diazoesters is presented, which is terminated with a formal [3 + 2] cycloaddition to give the bicyclic cyclopentadiene derivatives in high yields and selectivity.
TL;DR: For the first time α-diazocarbonyls have been used as highly active N-terminal electrophiles in the presence of bicyclic amidine catalysts, and the activation mode will lead to new synthetic applications of α-toxic methylene compounds.
Abstract: For the first time α-diazocarbonyls have been used as highly active N-terminal electrophiles in the presence of bicyclic amidine catalysts. The CN bond-forming reactions of active methylene compounds as C nucleophiles with α-diazocarbonyls as N-terminal electrophiles proceed quickly under ambient conditions, in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), because of the formation of the reactive N-terminal electrophilic intermediates. DBU activates both the active methylene and α-diazocarbonyl. Importantly, this reaction is general for both active methylenes and α-diazocarbonyls, and the activation mode will lead to new synthetic applications of α-diazocarbonyls.
TL;DR: The first Cu(II)-catalyzed highly enantioselective intramolecular cyclization of N-alkenylureas was developed for the concise assembly of chiral vicinal diamino bicyclic heterocycles.
TL;DR: A chiral bicyclic guanidine-catalyzed enantioselective sulfenylation of 3-substituted oxindoles to N-(sulfanyl)succinimides has been developed and a series of unprecedented 3-sulfenylated oxindole results were obtained.
Abstract: A chiral bicyclic guanidine-catalyzed enantioselective sulfenylation of 3-substituted oxindoles to N-(sulfanyl)succinimides has been developed. A series of unprecedented 3-sulfenylated oxindoles, such as 3-benzyl/alkyl-substituted 3-benzyl/alkyloxindoles, were obtained with high enantioselectivities (up to 98% ee). This methodology is also effective for the first asymmetric sulfenylation of benzofuran-2(3H)-ones, providing 3-benzyl-3-benzylthio-substituted benzofuran-2(3H)-ones with satisfactory results (up to 95% ee).
TL;DR: It is found that selected compounds 7d, 7e, 7n and 8c induced apoptosis, which was associated with the release of cytochrome c and cleavage of multiple caspases, and Overexpression of the protective mitochondrial protein Bcl-2 did not confer protection to cell death induced by these compounds.
TL;DR: Under ambient conditions, a [4 + 2] cycloaddition reaction of 1,3,2,5-diazadiborinine 1 with ethylene afforded a bicyclo[ 2.2.2] derivative 2, which was structurally characterized.
Abstract: Under ambient conditions, a [4 + 2] cycloaddition reaction of 1,3,2,5-diazadiborinine 1 with ethylene afforded a bicyclo[2.2.2] derivative 2, which was structurally characterized. The cyclization process was found to be reversible, and thus retro-[4 + 2] cycloaddition reproduced 1 quantitatively, concomitant with the release of ethylene. Compound 1 reacted regio-selectively and stereo-selectively with styrene derivatives and norbornene, respectively, and these processes were found to be reversible too. Computational studies determined the reaction pathways which were consistent with the regio-selectivity observed in the reaction of styrene, and the reaction was suggested to be essentially concerted but highly asynchronous.
TL;DR: It is shown by comprehensive multidimensional gas chromatography-mass spectrometry (GC×GC-MS), that >100 C8-15 bicyclic acids are typically present in OSPW, and the hypothesis is that these acids represent the biotransformation products of the initially somewhat more bio-resistant bicyclanes of petroleum.
Journal Article•
TL;DR: The precise placement of C-substituents on bicyclic and spirocyclic N-heterocycles is readily achieved by the combination of aldehydes and new SnAP reagents.
TL;DR: The method based on the selective aziridine opening by fluoride has been generalized to afford access to mono- or bicyclic fluorinated substances.
TL;DR: The biradical character of 3 indicates high reactivity which is further demonstrated in the activation of small molecules bearing multiple bonds leading to [2.2.1.1]bicyclic heterocycles.
Abstract: Diphosphadiazanediyl ([P(μ-NTer)]2, 1) is known to readily react with small molecules bearing multiple bonds to give [2.1.1]bicyclic species. On the contrary, in the reaction of isonitriles with 1, planar five-membered heterocycles (3) with biradical character are formed by insertion of the carbon atom into one P–N bond. Under irradiation, heterocyclic biradicaloids 3 are shown to generate housane-type [2.1.0]bicyclopentanes by transannular bond formation. However, these housane species thermally equilibrate, reforming the open-shell singlet cyclopentanediyl. The biradical character of 3 indicates high reactivity which is further demonstrated in the activation of small molecules bearing multiple bonds leading to [2.2.1]bicyclic heterocycles. Depending on the substituent of the isonitrile, the reaction with a second equivalent of isonitrile is also observed for smaller substituents. By employing suitable diisonitriles, even the catenation of two open-shell singlet cyclopentane-1,3-diyls is achieved. CASSCF...
TL;DR: The new bidentate oxazoline-carbene precursor with planar and central chirality had significant advantage than the bicyclic 1,2,4-triazolium salt derived from [2.2]paracyclophane as a monodentate carbene ligand in Cu(I)-catalyzed asymmetric β-boration of α,β-unsaturated esters, giving the desired products in high enantioselectivities and yields.
Abstract: A series of new oxazoline-substituted imidazolium salts based on [2.2]paracyclophane were synthesized and characterized. The new bidentate oxazoline-carbene precursor with planar and central chirality had significant advantage than the bicyclic 1,2,4-triazolium salt derived from [2.2]paracyclophane as a monodentate carbene ligand in Cu(I)-catalyzed asymmetric β-boration of α,β-unsaturated esters, giving the desired products in high enantioselectivities and yields.
Patent•
14 Jan 2015
TL;DR: In this article, the authors describe compounds of Formula (I) or a pharmaceutically acceptable salt thereof: Formula(I) wherein: (A) denotes a single or double bond; Warhead is a moiety capable of forming a covalent bond with a nucleophile.
Abstract: Described herein are compounds of Formula (I), or a pharmaceutically acceptable salt thereof: Formula (I) wherein: (A) denotes a single or double bond; Warhead is a moiety capable of forming a covalent bond with a nucleophile; Ring A is a 5-8 membered aryl, 5-12 membered heteroaryl, 3-7 member monocyclic or bicyclic heterocyclyl; or 3-12 membered monocyclic or bicyclic cycloalkyl group; W is C or N, X and Z are each independently CH or N; Y is CH or N-R 4 where R 4 is H, C 1-6 alkyl, or 3-12 membered cycloalkyl; each of R 1- R 3 is, independently, halo, cyano, optionally substituted C 1-6 alkyl, optionally substituted C 1-6 alkoxy, hydroxy, oxo, amino, amido, alkyl urea, optionally substituted 3-7 member heterocyclyl; R 7 is hydrogen or C 1-6 alkyl; or R 7 together with Ring A forms a 8-12 membered bicyclic heterocyclyl optionally substituted with 1-5 occurrences of R 1 ; m is 0-5; n is 0-5; and p is 0-2 as inhibitors of FGFR-4, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of FGFR-4.
TL;DR: A highly enantioselective desymmetrization of prochiral cyclopentenediones via Ag(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylide has been developed successfully and provides facile access to a series of highly functionalized bicyclic pyrrolidine/cyclopentane derivatives in good to high yields with excellent stereoselectivities.
TL;DR: 8dz was found to be an excellent catalyst precursor for the Ir-catalyzed asymmetric transfer hydrogenation of ketones, and proceeded smoothly to give corresponding alcohols with high enantioselectivities and productivities.
TL;DR: This work has used isothermal titration calorimetry-based binding experiments to study the interaction of the cocaine-binding aptamer to a series of structural analogs of quinine and found that the bicyclic aromatic ring on quInine is essential for tight affinity by the cocaine's aptamer with 6-methoxyquinoline alone being sufficient for tight binding.
TL;DR: A structure–activity relationship study suggested that the presence of an α,β-unsaturated carbonyl moiety is not essential for potent antimalarial activity.
Abstract: Antimalarial bioassay-guided fractionation of an EtOH extract of the root wood of Cryptocarya rigidifolia (Lauraceae) led to the isolation of the five new 5,6-dihydro-α-pyrones cryptorigidifoliols A–E (1–5) and the six bicyclic tetrahydro-α-pyrone derivatives cryptorigidifoliols F–K (6–11). The structure elucidations of all compounds were made on the basis of the interpretation of spectroscopic data and chemical derivatization, and the relative and absolute configurations were determined by NOESY, electronic circular dichroism (ECD), and 1H NMR analysis of α-methoxyphenylacetyl (MPA) derivatives. The bicyclic tetrahydro-α-pyrone derivatives were identified as products of acid-catalyzed intramolecular Michael addition of the 5,6-dihydro-α-pyrones in the presence of silica gel. A structure–activity relationship study suggested that the presence of an α,β-unsaturated carbonyl moiety is not essential for potent antimalarial activity.