Showing papers on "Claisen rearrangement published in 2019"
TL;DR: A metal-free intramolecular tandem sequence involving alkoxylation, Claisen rearrangement and lactone expansion has been achieved.
Abstract: Alkene carbooxygenation has attracted considerable attention over the past few decades as this approach provides an efficient access to various oxygen-containing molecules, especially the valuable O-heterocycles. However, examples of catalytic alkene carbooxygenation via a direct C–O cleavage are quite scarce, and the C–O cleavage in these cases is invariably initiated by transition metal-catalyzed oxidative addition. We report here a novel Bronsted acid-catalyzed intramolecular alkoxylation-initiated tandem sequence, which represents the first metal-free intramolecular alkoxylation/Claisen rearrangement. Significantly, an unprecedented Bronsted acid-catalyzed intramolecular alkene insertion into the C–O bond via a carbocation pathway was discovered. This method allows the stereocontrolled synthesis of valuable indole-fused bridged [4.2.1] lactones, providing ready access to biologically relevant scaffolds in a single synthetic step from an acyclic precursor. Moreover, such an asymmetric cascade cyclization has also been realized by employing a traceless chiral directing group. Control experiments favor the feasibility of a carbocation pathway for the process. In addition, biological tests showed that some of these newly synthesized indole-fused lactones exhibited their bioactivity as antitumor agents against different breast cancer cells, melanoma cells, and esophageal cancer cells.
48 citations
TL;DR: The Bacillus subtilis chorismate mutase catalysed Claisen rearrangement of chorismsate to prephenate is one of the few pericyclic processes in biology, and as such provides a rare opportunity for un...
Abstract: The Bacillus subtilis chorismate mutase catalysed Claisen rearrangement of chorismate to prephenate is one of the few pericyclic processes in biology, and as such provides a rare opportunity for un...
26 citations
TL;DR: The reaction kinetics show direct rearrangements of O-bound phospholene enolates and provide a proof-of-principle for catalytic enantioselective reactions.
Abstract: 1,3,2-Diazaphospholenes (DAPs) are an emerging class of organic hydrides. In this work, we exploited them as efficient catalysts for very mild reductive Claisen rearrangements. The method is tolerant towards a wide variety of functional groups and operates at ambient temperature. Besides being enantiospecific for substrates with existing stereogenic centers, the diastereoselectivity can be switched by varying solvents and DAP catalysts. The reaction kinetics show direct rearrangements of O-bound phospholene enolates and provide a proof-of-principle for catalytic enantioselective reactions.
22 citations
TL;DR: In going from AVE-(CO2)2 to chorismate, entropic effects due to rigidification and ring formation are operative, which lead to changes in the rate, and it is confirmed that C-O bond breaking precedes C-C bond formation in all cases.
Abstract: The Claisen rearrangement is a carbon-carbon bond-forming, pericyclic reaction of fundamental importance due to its relevance in synthetic and mechanistic investigations of organic and biological chemistry. Despite continued efforts, the molecular origins of the rate acceleration in going from the aqueous phase into the protein is still incompletely understood. In the present work, the rearrangement reactions for allyl-vinyl-ether (AVE), its dicarboxylated variant (AVE-(CO2)2), and the biologically relevant substrate chorismate are investigated in the gas phase, water, and in chorismate mutase. Only the rearrangement of chorismate in the enzyme shows a negative differential barrier when compared to the reaction in water, which leads to the experimentally observed catalytic effect for the enzyme. The molecular origin of this effect is the positioning of AVE-(CO2)2 and chorismate in the protein active site compared to AVE. Furthermore, in going from AVE-(CO2)2 to chorismate, entropic effects due to rigidification and ring formation are operative, which lead to changes in the rate. On the basis of "More O'Ferrall-Jencks" diagrams, it is confirmed that C-O bond breaking precedes C-C bond formation in all cases. This effect becomes more pronounced in going from the gas phase to the protein.
20 citations
TL;DR: A facile construction of α-allylbutenolides from readily available allyl ynoates has been developed via tandem gold-catalyzed alkyne isomerization to allene and cycloisomerization, the Claisen rearrangement and a double bond migration.
Abstract: A facile construction of α-allylbutenolides from readily available allyl ynoates has been developed via tandem gold-catalyzed alkyne isomerization to allene and cycloisomerization, the Claisen rearrangement and a double bond migration. The gold catalysis is enabled by a bifunctional phosphine ligand featuring a critical remote tertiary amino group, and the reaction tolerates a range of substituents and exhibits yields up to 96%.
18 citations
TL;DR: The first total synthesis of (+)-flavisiamine F is reported, which involved a room-temperature Overman rearrangement for introducing the chiral amine at C21, a TMS-promoted ketal Claisen rearrangements for constructing the all-carbon quaternary stereocenter at C20, and a late-stage visible-light-induced photochemical cyclization.
Abstract: The structural features Kopsia alkaloids, in particular multiple all-carbon quaternary stereocenters in a caged and strained polycyclic skeleton, poses particular challenges for enantioselective total synthesis. Herein, we reported the first total synthesis of (+)-flavisiamine F. The synthetic approach involved a room-temperature Overman rearrangement for introducing the chiral amine at C21, a TMS-promoted ketal Claisen rearrangement for constructing the all-carbon quaternary stereocenter at C20, and a late-stage visible-light-induced photochemical cyclization for establishing the all-carbon quaternary stereocenter at C7.
17 citations
TL;DR: An FeCl3-catalyzed allenic Claisen rearrangement/regio- and chemoselective aerobic dehydrogenative cyclization domino reaction is developed, providing a wide range of 2-aryl/alkyl, 3-(substituted-vinyl)naphtho[2,1- b]furans in high yields at 95-130 °C in an atom- and step-economic fashion.
16 citations
TL;DR: The tandem gold(I)-catalyzed propargyl Claisen rearrangement/hydroarylation reaction of suitable prop argyl vinyl ethers, followed by in situ reduction of the resulting carbonyl group, provides functionalized indenes in good to excellent yields.
Abstract: The tandem gold(I)-catalyzed propargyl Claisen rearrangement/hydroarylation reaction of suitable propargyl vinyl ethers, followed by in situ reduction of the resulting carbonyl group, provides functionalized indenes in good to excellent yields. The reaction occurs at room temperature in dichloromethane in the presence of 3 mol % [IPrAuCl]/AgBF4 as the best catalytic system. Instead, cyclization of the allene intermediate either does not take place or is very slow with phosphine ligands. A variety of substituents and functional groups present on the substrate are tolerated. The effect of the aryl ring substituents and the results of a density functional theory computational study suggest that the final hydroarylation is the rate-determining step of this cascade process. Further in situ chain elongation, prior final work up of the tandem process, can be carried out by Wittig olefination of the aldehyde functionality, thus incrementing the diversity of the products obtained.
13 citations
TL;DR: A divergent synthesis of functionalized 2,3-dihydrofuran and 2,2,2- dihydropyrrole derivatives via a LB-catalysed hydroalkoxylation/Claisen rearrangement/Michael addition tandem sequence is described.
13 citations
TL;DR: In the course of a total synthesis effort directed toward the natural product curcusone C, the Stoltz group discovered an unexpected thermal rearrangement of a divinylcyclopropane to the product of a formal Cope/1,3-sigmatropic shift sequence.
Abstract: In the course of a total synthesis effort directed toward the natural product curcusone C, the Stoltz group discovered an unexpected thermal rearrangement of a divinylcyclopropane to the product of a formal Cope/1,3-sigmatropic shift sequence. Since the involvement of a thermally forbidden 1,3-shift seemed unlikely, theoretical studies involving two approaches, the “trial-and-error” testing of various conceivable mechanisms (Houk group) and an “automatic” approach using the Maeda–Morokuma AFIR method (Morokuma group) were applied to explore the mechanism. Eventually, both approaches converged on a cascade mechanism shown to have some partial literature precedent: Cope rearrangement/1,5-sigmatropic silyl shift/Claisen rearrangement/retro-Claisen rearrangement/1,5-sigmatropic silyl shift, comprising a quintet of five sequential thermally allowed pericyclic rearrangements.
13 citations
TL;DR: A concise formal total synthesis of (-)-cephalotaxine was achieved via an ester enolate Claisen rearrangement (EECR) through a series of EECRs of proline allyl esters to obtain the desired relative stereochemistry of an azaspiranic tetracyclic backbone.
Abstract: A concise formal total synthesis of (-)-cephalotaxine was achieved via an ester enolate Claisen rearrangement (EECR). A series of EECRs of proline allyl esters were examined to obtain the desired relative stereochemistry of an azaspiranic tetracyclic backbone. An unexpected reversal or low diastereoselectivity of ( Z)-cinnamyl ester was observed. The diastereoselectivity was controlled by substitution patterns of a styrene region. This result represents a useful guide in aiding the prediction of stereochemical outcome of EECR of α-amino allylic esters.
TL;DR: These robust and practical processes furnished a series of architectures with a large chemical space, varying from planar to three-dimensional, and several interesting reactions were observed, such as [3 + 3] dimerization, quinone-based vinylogous Nazarov-type cyclization, and a rare 12e Mobius aromatic transition state mediated rearrangement.
14 Oct 2019
TL;DR: A new synthetic strategy to the ABCD ring system of the anticancer agent fredericamycin A (NSC-305263) was realized by the Diels–Alder reaction and olefin metathesis as key steps, accomplished without the involvement of protecting groups.
Abstract: A new synthetic strategy to the ABCD ring system of the anticancer agent fredericamycin A (NSC-305263) was realized by the Diels-Alder reaction and olefin metathesis as key steps. The tactics developed here for the construction of the ABCD ring system also involve double Claisen rearrangement followed by a retro-Diels-Alder reaction and ring-closing metathesis. The metathesis approach performs a key role in the construction of A and D rings of the ABCD core unit. More importantly, ABCD fragment synthesis was accomplished without the involvement of protecting groups.
TL;DR: Several functionalized cage propellanes and D3-trishomocubanes containing spiro linkage have been reported starting with commercially available materials such as 1,4-hydroquinone and dicyclopentadiene as discussed by the authors.
08 Jan 2019
TL;DR: An efficient protocol for the synthesis of γ,δ-unsaturated α-chloroketones has been developed via Au-catalyzed tandem intermolecular hydroalkoxylation/Claisen rearrangement, achieving high Z/E selectivity.
Abstract: An efficient protocol for the synthesis of γ,δ-unsaturated α-chloroketones has been developed via Au-catalyzed tandem intermolecular hydroalkoxylation/Claisen rearrangement. In the presence of 1 mol% JohnPhosAuCl and 1 mol% NaBArF, a broad range of allylic alcohols smoothly underwent the tandem intermolecular hydroalkoxylation/Claisen rearrangement with aromatic, vinylic or aliphatic chloroalkynes to give structurally diverse γ,δ-unsaturated α-chloroketones in excellent yields. Importantly, high Z/E selectivity was achieved. Other advantages are widespread availability of the substrates, compatibility with a broad range of functional groups and mild reaction conditions.
TL;DR: A total synthesis of an anticancer xanthone natural product termicalcicolanone A utilizing multiple nucleophilic aromatic substitutions and pericyclic reactions has been developed.
TL;DR: The first systematic investigation of the tandem mercury(ii) catalysed transvinylation/Hurd-Claisen rearrangement of MBH adducts derived from alkyl acrylates with E-selectivity is reported, complementary to the previously reported Johnson- Claisen and Eschenmoser-Cla Eisen rearrangements.
Abstract: Herein we report the first systematic investigation of the tandem mercury(II) catalysed transvinylation/Hurd–Claisen rearrangement of MBH adducts derived from alkyl acrylates. This is the first report of E-selectivity for MBH adducts with alkyl side chains and is complementary to the previously reported Johnson–Claisen and Eschenmoser–Claisen rearrangements. The rearrangement products were obtained in good yields and could be readily converted to 2-alkenyl δ-valerolactones. Combined DFT and F-SAPT studies demonstrate that reaction rates are primarily governed by non-covalent interactions dictating the relative stability of the transition states. Our F-SAPT calculations revealed that the hyperconjugative effects are not so significant, but that electrostatic interactions, instead, are the driving forces for the relative E : Z stereoselectivity.
TL;DR: This synthetic method for 1,1-captodative dienes, α-substituted 2,4-dienamides, can be utilized for preparing pharmaceutical analogues containing an indolin-2-one or lactone moiety.
TL;DR: A concise, unified total synthesis of the two prenylated aromatic polyketides amorfrutins A and C, which exhibit various medicinally important biological profiles such as antimicrobial, PPARγ modulating and quorum sensing inhibitory activities, has been achieved from commercially available 3,5-dimethoxybenzaldehyde.
Abstract: A concise, unified total synthesis of the two prenylated aromatic polyketides amorfrutins A and C, which exhibit various medicinally important biological profiles such as antimicrobial, PPARγ modulating and quorum sensing inhibitory activities, has been achieved from commercially available 3,5-dimethoxybenzaldehyde in 38% and 10% overall yields through nine and ten steps, respectively. The key transformation for the synthesis of amorfrutin A was the Claisen rearrangement of a mono-O-(1,1-dimethylallyl)resorcinol derivative to install the C3-prenyl substituent, while that for the synthesis of amorfrutin C was the double Claisen rearrangement of a di-O-(1,1-dimethylallyl)resorcinol derivative to introduce the two prenyl groups at the C3 and C5 positions all at once.
TL;DR: A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps, and a Claisen rearrangement reaction is described in scaled flow at multigram amounts.
Abstract: A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps. First, a Claisen rearrangement reaction is described in scaled flow at multigram amounts. Yields and selectivity of this step are sharply improved compared to those from previous syntheses. Second, the key Pauson–Khand reaction in flow is described under catalytic conditions with 5 mol% of cobalt carbonyl and only 3 equiv. of CO. Scaling up of this reaction safely ensures a good yield of an advanced intermediate which is transformed into treprostinil in three steps. Other improvements are the introduction of the carboxymethyl chain into the phenol from the beginning to reduce the protection–deprotection steps. The synthesis is completed in 14% global yield after 12 linear steps from (S)-epichlorhydrin.
TL;DR: The first total synthesis of (±)-floribundane B was reported in this paper, where the Johnson-Claisen rearrangement of a Morita-Baylis-Hillman adduct assembled all of the stereochemical features of this secoiridoid.
TL;DR: The combination of a resonance stabilized DcA reaction with a Claisen rearrangement for the synthesis of multisubstituted phenols and applying to dihydroplicatin B derivative synthesis is also presented.
Abstract: A strategy toward the preparation of substituted allyl aryl ethers from benzoic acids via a dearomatization and decarboxylative allylation (DcA) reaction is presented. The benzoic acids undergo a dearomatization to give alkylated 2,5-cyclohexadienyl ketoesters which are subjected to a palladium-catalyzed DcA reaction, providing a variety of functionalized allyl aryl ethers. In addition, the combination of a resonance stabilized DcA reaction with a Claisen rearrangement for the synthesis of multisubstituted phenols and applying to dihydroplicatin B derivative synthesis is also presented.
TL;DR: It is observed that a data sampling scheme that combined partial geometry optimization of intermediate structures with random displacement of atoms successfully predicted the energies along the reaction path with respect to five chemical reactions.
Abstract: We propose a data sampling scheme for high-dimensional neural network potentials that can predict energies along the reaction pathway calculated using the hybrid density functional theory. We observed that a data sampling scheme that combined partial geometry optimization of intermediate structures with random displacement of atoms successfully predicted the energies along the reaction path with respect to five chemical reactions: Claisen rearrangement, Diels–Alder reaction, [1,5]-sigmatropic hydrogen shift, concerted hydrogen transfer in the water hexamer, and Cornforth rearrangement.We propose a data sampling scheme for high-dimensional neural network potentials that can predict energies along the reaction pathway calculated using the hybrid density functional theory. We observed that a data sampling scheme that combined partial geometry optimization of intermediate structures with random displacement of atoms successfully predicted the energies along the reaction path with respect to five chemical reactions: Claisen rearrangement, Diels–Alder reaction, [1,5]-sigmatropic hydrogen shift, concerted hydrogen transfer in the water hexamer, and Cornforth rearrangement.
TL;DR: In this paper, a chiral 1,3-substituted allene entity was achieved using (R)-but-3-yn-2-ol. The details of the work are elaborately discussed in this paper.
TL;DR: In this article, the rearrangement is influenced by stereoelectronic effects of substituents present in 1-N-allylindolines and ZnCl2 catalyst loading in the reaction system.
Abstract: Abstract 7-Allylindolines are valuable synthons for designing biologically active molecular libraries. Lewis acid catalyzed amino-Claisen rearrangement provides a one pot synthetic entry to these heteroarenes. In this context, Zinc chloride (ZnCl2)–N,N-dimethylformamide system efficiently catalyzed amino-Claisen rearrangements of 1-N-allylindolines to 7-allylindolines. The rearrangement is influenced by stereoelectronic effects of substituents present in 1-N-allylindolines. The substrates containing electron donating functionalities underwent rearrangement at lower temperature than substrates with electron withdrawing functional groups. The regioselectivity of the process is governed by the substitution pattern on allyl moiety in 1-N-allylindoline as well as ZnCl2 catalyst loading in the reaction system.
TL;DR: In this article, a 40% KF/Al2O3-mediated hydroacylation of a 2-allyl-benzaldehyde derivative, obtained in two steps from isovanillin, through O-allylation and Claisen rearrangement, was reported.
Abstract: A straightforward approach toward a decorated cyclopenta[ij]isoquinoline embodying the ABC-ring system characteristic of the azafluoranthene (triclisine), tropoisoquinoline (pareitropone) and proaporphine (prodensiflorin B) alkaloids, is reported. The synthetic sequence entailed a novel 40% KF/Al2O3-mediated hydroacylation of a 2-allyl-benzaldehyde derivative, obtained in two steps from isovanillin, through O-allylation and Claisen rearrangement to assemble the AC-ring system. This was followed by an O-methylation and a reductive amination of the resulting indanone with aminoacetal. A modified Pomeranz–Fritsch cyclization was next implemented to install ring B, through sulfonamidation, followed by acid-promoted cyclization and final desulfonylation in situ.
TL;DR: In this article, a hexakis-4-(2-(4-((β-methallyl)oxy)phenyl)propan-2-yl)phenoxycyclotriphosphazene was synthesized via the reaction of methallyl chloride with bisphenol A.