Showing papers on "Claisen rearrangement published in 2018"
TL;DR: This is the first total synthesis of 1 featuring a late-stage intermolecular Diels-Alder reaction of a fully elaborated cyclopentadiene and asperuloside tetraacetate and the diene was prepared on the basis of a scalable route to daphnilongeranin B.
Abstract: Hybridaphniphylline B (1) is a Daphniphyllum alkaloid possessing 11 rings and 19 stereocenters. Here we report the first total synthesis of 1 featuring a late-stage intermolecular Diels–Alder reaction of a fully elaborated cyclopentadiene and asperuloside tetraacetate. The diene was prepared on the basis of a scalable route to daphnilongeranin B (4). Claisen rearrangement of an allyl dienol ether was exploited as a key step; the subtle variation of the substrate and use of protic solvents suppressed the undesired Cope rearrangement. Daphniyunnine E (6) and dehydrodaphnilongeranin B (7), two congeners of 4, were also synthesized. The dienophile arose from (+)-genipin through glycosylation and lactonization. A one-pot protocol was developed for the diene formation and Diels–Alder reaction; one of the cycloadducts was converted into 1 through reductive desulfurization and global deacetylation.
73 citations
TL;DR: A nickel-catalyzed enantioselective dearomatization Claisen rearrangement leading to vicinal all-carbon stereocentres is reported and applied to the stereodivergent synthesis of bioactive hyperolactones.
Abstract: Although great success has been achieved in asymmetric Claisen rearrangement for the synthesis of chiral γ,δ-unsaturated carbonyl compounds bearing vicinal tertiary-quaternary stereocenters, the development of asymmetric versions for stereodivergent construction of adjacent quaternary-quaternary stereocenters remains a formidable challenge because of the high steric hindrance. Here we report a catalytic enantioselective dearomatization Claisen rearrangement of allyl furyl ethers catalyzed by chiral N,N′-dioxide-NiII complex catalysts. A variety of chiral γ,δ-unsaturated carbonyl compounds bearing vicinal quaternary-quaternary stereocenters were obtained with excellent outcomes under mild conditions. Furthermore, we disclosed that by matching the configuration of the catalysts and the alkene unit of the substrates, four stereoisomers of the products could be prepared in excellent yields and stereoselectivities. Finally, the fascination of this strategy was demonstrated by stereodivergent synthesis of bioactive natural products hyperolactones B, C, and their epimers. A possible catalytic model was proposed to explain the origin of the asymmetric induction. Stereodivergent construction of adjacent quaternary-quaternary stereocenters remains a formidable synthetic challenge. Here, the authors report a nickel-catalyzed enantioselective dearomatization Claisen rearrangement leading to vicinal all-carbon stereocentres and apply it to the stereodivergent synthesis of bioactive hyperolactones.
52 citations
TL;DR: Possible transition state models were proposed to elucidate the origin of chiral induction based on the control experiments and X-ray crystal structure of the catalyst to provide a straight and facile route to various enantioenriched β/γ-amino acid derivatives.
Abstract: The first example of catalytic insertion/asymmetric Claisen rearrangement tandem reaction of N-sulfonyl-1,2,3-triazoles with allyl alcohol esters was achieved by bimetallic relay catalytic systems involving achiral rhodium salt and chiral N,N'-dioxide-indium(III) complex. This manifold could overcome the limitation of single RhII catalysis, providing a straight and facile route to various enantioenriched β/γ-amino acid derivatives in high yields (up to 99 %) with excellent diastereo- and enantioselectivities (up to >95:5 dr, 98:2 er). Moreover, possible transition state models were proposed to elucidate the origin of chiral induction based on the control experiments and X-ray crystal structure of the catalyst.
50 citations
TL;DR: Hongkonoids A-D (1-4), the first example of ascorbylated terpenoids featuring a unique 5,5,5-fused tricyclic spiroketal butyrolactone moiety and diterpenoid-derived long chain, were isolated from Dysoxylum hongkongense.
Abstract: Hongkonoids A–D (1–4), the first example of ascorbylated terpenoids featuring a unique 5,5,5-fused tricyclic spiroketal butyrolactone moiety and diterpenoid-derived long chain, were isolated from Dysoxylum hongkongense. Their structures were unambiguously assigned by a combination of spectroscopic data, chemical degradation, X-ray crystallography, CD analysis, and total synthesis. The total syntheses of compounds 1–4 were effectively accomplished by a convergent strategy with the longest linear sequences of 12–14 steps and overall yields of 5.4–9.6%. Notably, we exploited a bioinspired one-pot method to construct the key intermediate 14 from an easily made compound 12 by involving the cascade reactions of an elaborate Claisen rearrangement, deprotections, and a 5-exo-trig cyclization. The desired major epimer 14a was then transformed to the main building block 21. Assembly of 21 and the long chain vinyl iodide 7 was made by an NHK coupling reaction to furnish the framework of 1–4. Some of the hongkonoids ...
30 citations
TL;DR: In this article, the Johnson-Claisen rearrangement of allyl alcohol and triethyl orthoacetate with a continuous flow apparatus combined with a microwave reactor was demonstrated.
26 citations
TL;DR: Several naturally occurring 8-prenylcoumarins that were previously inaccessible have been synthesized in good overall yields along this route.
Abstract: The one-pot synthesis of 8-prenylcoumarins from 1,1-dimethylallylated salicylaldehydes and the stabilized ylide [(ethoxycarbonyl)methylene]triphenylphosphorane under microwave conditions was found to have a limited scope. The sequence suffers from a difficult and sometimes low-yielding synthesis of the precursors and from a competing deprenylation upon microwave irradiation. This side reaction occurs in particular with electron rich arenes with two or more alkoxy groups at adjacent positions, a prominent substitution pattern in naturally occurring 8-prenylcoumarins. Both limitations of this one-step sequence were overcome by a two-step synthesis consisting of a microwave-promoted tandem allyl ether Claisen rearrangement/Wittig olefination and a subsequent olefin cross metathesis with 2-methyl-2-butene. The cross metathesis step proceeds with a high selectivity and yields exclusively the desired prenyl, rather than the alternative crotyl substituent. Several naturally occurring 8-prenylcoumarins that were previously inaccessible have been synthesized in good overall yields along this route.
25 citations
TL;DR: A cascade Claisen rearrangement of a well-organized maltol propargyl ether for the construction of polysubstituted salicylaldehydes is reported, which features high atom economy (100 %), as well as catalyst-free and gram-scale conditions.
Abstract: A cascade Claisen rearrangement of a well-organized maltol propargyl ether for the construction of polysubstituted salicylaldehydes is reported. This reaction features high atom economy (100 %), as well as catalyst-free and gram-scale conditions. Based on this novel methodology, the total synthesis of hemigossypol, gossypol, and their analogues has been realized.
25 citations
TL;DR: A diastereoselective approach for the total synthesis of an unusual atropisomer of the Schisandra triterpenoid (±)-schiglautone A is described.
Abstract: A diastereoselective approach for the total synthesis of an unusual atropisomer of the Schisandra triterpenoid (±)-schiglautone A is described. The efficient synthetic strategy features three key transformations: 1) two sequential titanium(III)-catalyzed radical cyclization/homologation reactions to construct the trans-fused [6,7] bicycle as well as install the quaternary carbons at C10 and C14 with the desired stereochemistry; 2) a Claisen rearrangement followed by a ring-closing metathesis to forge the strained nine-membered ring; and 3) a substrate-controlled Michael addition to enable the introduction of the C17 side-chain with good diastereoselectivity.
23 citations
TL;DR: An unprecedented base-mediated cyclization of propargylic alcohols with aryne is reported, providing a novel method for the synthesis of 3-benzofuranyl-2-oxindole and 3-spirooxindoles benzofuran scaffolds via a propargyl Claisen rearrangement/cycloaddition pathway.
23 citations
TL;DR: The reaction of arynes and secondary allylamines furnished ortho-allyl-substituted N-arylanilines via an aza-Claisen rearrangement and were converted into aryl-fused medium-sized nitrogenous heterocyclic molecules such as azepines, azocines and azonines via ring-closing metathesis (RCM).
Abstract: The reaction of arynes and secondary allylamines furnished ortho-allyl-substituted N-arylanilines via an aza-Claisen rearrangement. In this transformation, the sequential formation of C–C and C–N bonds occurred by involving two aryne molecules under metal-free reaction conditions to provide moderate to good yields of the products. The obtained ortho-allyl-substituted N-arylaniline derivatives were further converted into aryl-fused medium-sized (7–9) nitrogenous heterocyclic molecules such as azepines, azocines and azonines via ring-closing metathesis (RCM).
21 citations
TL;DR: An enantioselective convergent synthesis of thailanstatin A methyl ester and evaluation of its splicing activity are described, which proved to be a potent inhibitor of the spliceosome.
Abstract: Thailanstatin A has been isolated recently from the fermentation broth of B. thailandensis MSMB43. We describe here an enantioselective convergent synthesis of thailanstatin A methyl ester and evaluation of its splicing activity. Synthesis of both highly functionalized tetrahydropyran rings were carried out from commercially available tri-O-acetyl-d-glucal as the key starting material. Our convergent synthesis involved the synthesis of both tetrahydropyran fragments in a highly stereoselective manner. The fragments were then coupled using cross-metathesis as the key step. The synthesis of the diene subunit included a highly stereoselective Claisen rearrangement, a Cu(I)-mediated conjugate addition of MeLi to set the C-14 methyl stereochemistry, a reductive amination reaction to install the C16-amine functionality, and a Wittig olefination reaction to incorporate the diene unit. The epoxy alcohol subunit was synthesized by a highly selective anomeric allylation, a Peterson olefination, and a vanadium catal...
TL;DR: In this paper, a single-mode microwave reactor for continuous flow synthesis with various methods of operation was developed, which measures the resonant frequency and modulates the oscillation frequency accordingly to maintain the maximum electric field intensity in the cavity.
Abstract: We have developed a single-mode microwave reactor for continuous-flow synthesis with various methods of operation. This device measures the resonant frequency and modulates the oscillation frequency accordingly to maintain the maximum electric field intensity in the cavity. It can be operated either using constant applied irradiation power or using new programs which change the electric power (E-GRA) and change the flow rate (Fl-GRA), in order to rapidly screen various reaction conditions. As a model reaction, the Claisen rearrangement reaction of allyl 1-naphthyl ether 1 was rapidly optimized in this device, affording the desired product 2-allylnapthalen-1-ol 2 in high (91%) yield and up to 20 g/h productivity.
TL;DR: The tandem gold(I)-catalyzed propargyl Claisen rearrangement/Nazarov cyclization of propargylic vinyl ether derivatives, followed by in situ reduction of the resulting carbonyl group, provides functionalized cyclopentadienes fused with various N-hetero- and carbacycles, including indoles, in good to excellent yields.
TL;DR: Pyrano[2,3-f]chromene-2,8-diones were inaccessible through direct RCM of an acrylate, but became available from the analogous allyl ether via an assisted tandem catalytic RCM/allylic oxidation sequence.
Abstract: 8-Allylcoumarins are conveniently accessible through a microwave-promoted tandem Claisen rearrangement/Wittig olefination/cyclization sequence. They serve as a versatile platform for the annellation of five- to seven-membered rings using ring-closing olefin metathesis (RCM). Furano-, pyrano-, oxepino- and azepinocoumarins were synthesized from the same set of precursors using Ru-catalyzed double bond isomerizations and RCM in a defined order. One class of products, pyrano[2,3-f]chromene-2,8-diones, were inaccessible through direct RCM of an acrylate, but became available from the analogous allyl ether via an assisted tandem catalytic RCM/allylic oxidation sequence.
TL;DR: In this paper, a 3,3′-sigmatropic Claisen rearrangement for functionalization of polyamides and allyl-derivatives with different functional groups and rigidity is presented.
TL;DR: The use of the electron localization function (ELF) is presented to monitor the bonding evolution aspects in the course of this thermal rearrangement and the results are compared with a photo-impulsive process where instantaneous vibration frequencies are monitored.
Abstract: A comprehensive theoretical investigation of the thermal Claisen rearrangement of allyl vinyl ether (AVE) to allylacetaldehyde has been carried out. We present the use of the electron localization function (ELF) to monitor the bonding evolution aspects in the course of this thermal rearrangement and the results are compared with a photo-impulsive process where instantaneous vibration frequencies are monitored [I. Iwakura, Phys. Chem. Chem. Phys., 2011, 12, 5546-5555]. Our results reveal an asynchronous electron density rearrangement inasmuch that the breaking of the C3-O bond and the formation of C1-C5 do not take place simultaneously. We also demonstrate how the bonding evolution brings about the natural appearance of the curly arrows representing the electronic flow in molecular rearrangements. This holds the key to gaining an unprecedented insight into the mapping of the electron density flow while the bonds change throughout the reaction progress.
TL;DR: Several new synthetic methods to diverse polycycles and heterocycles on the basis of [3,3]-sigmatropic rearrangement and ring-closing metathesis as key steps are summarized in this article.
Abstract: Several new synthetic methods to diverse polycycles and heterocycles on the basis of [3,3]-sigmatropic rearrangement and ring-closing metathesis as key steps are summarized. In this regard, Claisen, aza-Claisen, and Overman rearrangements are used in combination with other popular reactions such as ring-closing metathesis, Suzuki coupling, Diels-Alder reaction, and retro-Diels-Alder reaction. To this end, we prepared polycycles (e.g., cyclophanes, cage molecules), heterocycles (e.g., oxepins, azapins), carbocycles, and spirocycles with the use of the above protocol.
TL;DR: In this paper, the authors present a short synthesis of the suitably functionalized enantioselective dihydropyran core of secoiridoids using an N-heterocyclic carbene (NHC) catalyzed Coates-Claisen rearrangement mechanism.
Abstract: We present the short synthesis of the suitably functionalized enantioselective dihydropyran core of secoiridoids using an N-heterocyclic carbene (NHC) catalyzed Coates-Claisen rearrangement mechanism. The key steps of the synthesis are (i) the highly enantioselective NHC catalyzed Coates-Claisen rearrangement for the dihydropyran core, (ii) the assembly of the target dihydropyran core structure of oleuropein from a highly diastereoselective exocyclic trans alkene, and (iii) the highly stereoselective assembly of a monoterpene elenolide core structure.
TL;DR: An efficient reaction utilizing propargyl carbonates through Claisen rearrangement to synthesize furanonaphthoquinones is described, exhibiting excellent functional group tolerance, affording the targets in moderate to good yields under mild reaction conditions.
Abstract: An efficient reaction utilizing propargyl carbonates through Claisen rearrangement to synthesize furanonaphthoquinones is described. The remarkable transformation exhibits excellent functional group tolerance, affording the target furanonaphthoquinones in moderate to good yields (41–85%) under mild reaction conditions. Scaled-up preparation of the model product can make this reaction a method of choice for synthesis of furanonaphthoquinone derivatives. The resulting furanonaphthoquinones were evaluated as potential indoleamine 2,3-dioxygenase inhibitors in vitro.
TL;DR: This work reviews the rearrangement of both benzylic and heterobenzylic substrates, with examples of the reaction’s use in the synthesis of natural products and drug-like molecules.
Abstract: The Claisen rearrangement of benzylic substrates (benzyl vinyl ethers) has received considerably less attention than its well-known aliphatic and normal aromatic variants. Here, we review the rearrangement of both benzylic and heterobenzylic substrates, with examples of the reaction’s use in the synthesis of natural products and drug-like molecules. 1 Introduction 2 Early Attempts at the Benzyl-Claisen Rearrangement 3 Successful Benzylic Examples 4 Heterobenzylic Examples 5 Conclusion
TL;DR: A joint application of bonding evolution theory and non-covalent interaction (NCI) analysis provides a powerful tool to explain the molecular mechanism of organic reactions as mentioned in this paper. But it is not suitable for the analysis of proteins.
TL;DR: A series of half-sandwich ruthenium(II) complexes containing 2-phenylethanol and 3-phenylpropanol ligands were investigated as catalysts for the tandem isomerization/Claisen rearrangement of diallyl ethers into γ,δ-unsaturated aldehydes using, for the first time, water as solvent as mentioned in this paper.
TL;DR: The PPTS-catalyzed intramolecular diastereoselective Henry reaction to fix three contiguous stereocenters on tetrahydronaphthalene and the first-of-its-kind synthesis of the 3-azidopiperidine skeleton, using a CAN-mediated regioselectives azidoalkoxylation of enol ether, are important findings of the present work.
TL;DR: In this article, an approach to the 6/5/6/7 tetracyclic core scaffold of C18/C19 diterpenoid alkaloids and phomopsterone B was presented.
Abstract: A concise and efficient approach to the core of the C18/C19 diterpenoid alkaloids and phomopsterone B is reported. Both syntheses share the same iron-catalyzed intramolecular [5+2] cycloaddition to assemble the tricyclo[6.3.1.01,6]]dodecane skeleton. The following approach to the 6/5/6/7 tetracyclic core scaffold of C18/C19 diterpenoid alkaloids features a regioselective Grignard addition/thermal Claisen rearrangement/RCM cyclization. Meanwhile the synthetic steps to access the spiro 6/5/6 tricyclic subunits of phomopsterone B were characterized as intramolecular aldol reaction, Wacker oxidation, and Criegee reaction.
TL;DR: The computational results led to the development of Pd(II)-catalyzed [3,3]-sigmatropic rearrangement of 3-aryl substituted 2-propargylindoles, and subsequent experimental kinetic isotope effects are in accord with the mechanism derived from the computations.
TL;DR: In this paper, a ring-closing metathesis of novel pyrazole-fused heterocycles, i.e., dihydro-1H- or 2H-oxepino[3,2-c] pyrazoles (6 or 7) from 4-allyloxy-1-h-pyrazoles, via combination of Claisen rearrangement and ringclosing meeting at room temperature, has been achieved.
Abstract: Synthesis of novel pyrazole-fused heterocycles, i.e., dihydro-1H- or 2H-oxepino[3,2-c]pyrazoles (6 or 7) from 4-allyloxy-1H-pyrazoles (1) via combination of Claisen rearrangement and ring-closing metathesis (RCM) has been achieved. A suitable catalyst for the RCM of 5-allyl-4-allyloxy-1H-pyrazoles (4) was proved to be the Grubbs second generation catalyst (Grubbs2nd) to give the predicted RCM product at room temperature in three hours. The same reactions of the regioisomer, 3-allyl-4-allyloxy-1H-pyrazoles (5), also proceeded to give the corresponding RCM products. On the other hand, microwave aided RCM at 140 °C on both of 4 and 5 afforded mixtures of isomeric products with double bond rearrangement from normal RCM products in spite of remarkable reduction of the reaction time to 10 min.
TL;DR: In this paper, a general approach to computational investigation of reaction pathways with Natural Resonance Theory (NRT) is described, allowing synthetic strategies to incorporate insights from modern quantum chemical descriptors, and they show how computed NRT weightings and bond orders provide resonance-type visualization of the electronic sequence and logic of complex bond rearrangements along a reaction pathway.
TL;DR: The results suggested that the compound grandione is formed via a H-DA/retro-Claisen rearrangement and not by the traditional H- DA mechanism proposed early in the experimental studies.
Abstract: Mechanistic theoretical studies about the feasibility of the traditional proposed mechanism of formation for icetexane diterpene dimer grandione were assessed using density functional method at the M06-2X/6-31G(d,p) level of theory. Bulk water solvent effects were taken into account implicitly using the polarizable continuum model (SCI-PCM). The results were compared with the selectivity found in the biomimetic synthesis performed by experimental research groups. The relative free energy calculation shows that the one-step H-DA formation mechanism nominated in the literature is not a viable mechanism. We found that an alternative competing Tandem pathway is consistent with the experimental trends. Thus, our results suggested that the compound grandione is formed via a H-DA/retro-Claisen rearrangement and not by the traditional H-DA mechanism proposed early in the experimental studies. The H-DA initial step produce a biecyclic adduct followed by a domino retro-Claisen rearrangement that releases the energy strain of the bicyclic intermediary. Steric issues and hyperconjugation interactions are the mainly factors driving the reaction nature and the selectivity in the formation reaction. Finally, the enzymatic assistance for dimer formation was analyzed in terms of the calculated transition state energy barrier.
TL;DR: In this article, the de novo asymmetric total synthesis of (−)-nanaomycin A was described, which required only 13 steps from commercially available starting materials (3% overall yield).