Showing papers on "Claisen rearrangement published in 2003"
TL;DR: A practical method for the diastereoselective generation of two adjacent quarternary stereocenters by combining a copper-catalyzed C-O coupling reaction with a subsequent Claisen rearranged in a one-pot domino process is described.
Abstract: A practical method for the diastereoselective generation of two adjacent quarternary stereocenters by combining a copper-catalyzed C−O coupling reaction with a subsequent Claisen rearrangement in a one-pot domino process is described. Furthermore, an experimentally simple method for the stereoselective synthesis of a variety of different types of vinyl ethers is delineated using the same catalyst system.
167 citations
TL;DR: This work has achieved the first asymmetric total synthesis from 2-acetoxy-tri-O-acetyl-d-glucal as a chiral starting material and selected the protective groups to accomplish the total synthesis of tetrodotoxin in an enantiomerically pure form.
Abstract: Tetrodotoxin, a toxic principle of puffer fish poisoning, is one of the most famous marine natural products because of the complex structure having many functional groups and its potent biological activity leading to death. Since the structure elucidation in 1964, this toxin has been recognized as a formidable target molecule for total synthesis. We have recently achieved the first asymmetric total synthesis from 2-acetoxy-tri-O-acetyl-d-glucal as a chiral starting material. The highly hydroxylated cyclohexane ring was constructed by Claisen rearrangement and regioselective hydroxylations of an acetone moiety and an intramolecular directed aldol condensation of the precursor having methyl ketone with dihydroxyacetone, which was synthesized through Sonogashira coupling. Installation of nitrogen functionality was unsuccessful through an attempted Overman rearrangement. We, therefore, employed a new intramolecular conjugate addition strategy between the carbamate and unsaturated ester groups. The alpha-hydroxyl lactone moiety was synthesized through an intramolecular epoxide opening by the Z-enolate of aldehyde, which was followed by oxidation-reduction of the resulting cyclic vinyl ether. The lactone was then converted to a protected ortho ester, and then gunanidinylation was followed by cleavage of the 1,2-glycol to give the fully protected tetrodotoxin. Selection of the protective groups has finally led us to accomplish the total synthesis of tetrodotoxin in an enantiomerically pure form. All the stereogenic centers were controlled with high selectivity, and the hydroxyl groups were differently protected to discriminate for the future analogue synthesis of a bioorganic program. The synthetic tetrodotoxin was purified by ion exchange chromatography and characterized to be identical with the natural compound.
158 citations
TL;DR: Standard free energies were calculated for the Claisen rearrangement of chorismate to prephenate in six different environments: water, wild-type enzymes from Bacillus subtilis and Escherichia coli, their Arg90Cit and Glu52Ala mutants, and the 1F7 catalytic antibody.
Abstract: Standard free energies (ΔGN°) for formation of near attack conformers, those ground state conformers that can convert directly to the transition state, were calculated for the Claisen rearrangement of chorismate to prephenate in six different environments: water, wild-type enzymes from Bacillus subtilis and Escherichia coli, their Arg90Cit and Glu52Ala mutants, and the 1F7 catalytic antibody. Values of the calculated ΔGN°s and the experimentally determined activation energies (ΔG‡) are linearly related with the slope of ≈1. This demonstrates that the relative rate of the chorismate → prephenate reaction is overwhelmingly dependent on the efficiency of formation of near attack conformers in the ground state.
151 citations
TL;DR: In this article, a replica path method for complex systems involving hybrid quantum/classical (quantum mechanical/molecular mechanical) coupled potentials is proposed, which involves the definition of a reaction path via replication of a set of macromolecular atoms.
Abstract: A replica path method has been developed and extended for use in complex systems involving hybrid quantum/classical (quantum mechanical/molecular mechanical) coupled potentials. This method involves the definition of a reaction path via replication of a set of macromolecular atoms. An “important” subset of these replicated atoms is restrained with a penalty function based on weighted root-mean-square rotation/translation best-fit distances between adjacent (i±1) and next adjacent (i±2) pathway steps. An independent subset of the replicated atoms may be treated quantum mechanically using the computational engine Gamess-UK. This treatment can be performed in a highly parallel manner in which many dozens of processors can be efficiently employed. Computed forces may be projected onto a reference pathway and integrated to yield a potential of mean force (PMF). This PMF, which does not suffer from large errors associated with calculated potential-energy differences, is extremely advantageous. As an example, the QM/MM replica path method is applied to the study of the Claisen rearrangement of chorismate to prephenate which is catalyzed by the Bacillus subtilis isolated, chorismate mutase. Results of the QM/MM pathway minimizations yielded an activation enthalpy ΔH
†† of 14.9 kcal/mol and a reaction enthalpy of −19.5 kcal/mol at the B3LYP/6-31G(d) level of theory. The resultant pathway was compared and contrasted with one obtained using a forced transition approach based on a reaction coordinate constrained repeated walk procedure (ΔH
†† =20.1 kcal/mol, ΔH
rxn = −20.1 kcal/mol, RHF/4-31G). The optimized replica path results compare favorably to the experimental activation enthalpy of 12.7±0.4 kcal/mol.
100 citations
TL;DR: Iridium(I)-catalyzed olefin isomerization in bis(allyl) ethers is integrated into a generally applicable strategy for affecting highly stereoselective Claisen rearrangements.
Abstract: Iridium(I)-catalyzed olefin isomerization in bis(allyl) ethers is integrated into a generally applicable strategy for affecting highly stereoselective Claisen rearrangements. Catalyzed alkene isomerization affords allyl vinyl ethers from easily prepared di(allyl) ethers; direct thermolysis of these reaction mixtures leads to highly diastereoselective [3,3] sigmatropic rearrangements affording syn-2,3-dialkyl-4-pentenal derivatives. An easily executed strategy for realizing asymmetric variants of the isomerization-Claisen rearrangement (ICR) reactions is also described.
90 citations
TL;DR: A regioselective and enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical allylic alcohol derivatives using copper(I) enolates to prepare beta-substituted ketones to represent a convenient asymmetric Claisen rearrangement surrogate.
Abstract: The transition metal-catalyzed allylic alkylation represents a fundamentally important cross-coupling reaction for the construction of ternary carbon stereogenic centers. We have developed a regioselective and enantiospecific rhodium-catalyzed allylic alkylation of acyclic unsymmetrical allylic alcohol derivatives using copper(I) enolates to prepare β-substituted ketones. This protocol represents a convenient asymmetric Claisen rearrangement surrogate in which α-substituted enolates permit the introduction of an additional stereogenic center. The synthetic utility of this transformation was highlighted in the construction of a trans-1,2-disubstituted cyclohexene and the total synthesis of (−)-sugiresinol dimethyl ether. Finally, we anticipate that copper(I) enolates may prove useful nucleophiles in related metal-catalyzed reactions.
77 citations
TL;DR: The Claisen rearrangement of chorismate to prephenate in the enzyme has been modelled here by a combined quantum mechanics/molecular mechanics (QM/MM) method, indicating that this is central to catalysis by the enzyme.
Abstract: Chorismate mutase provides an important test of theories of enzyme catalysis, and of modelling methods. The Claisen rearrangement of chorismate to prephenate in the enzyme has been modelled here by a combined quantum mechanics/molecular mechanics (QM/MM) method. Several pathways have been calculated. The sensitivity of the results to details of model preparation and pathway calculation is tested, and the results are compared in detail to previous similar studies and experiments. The potential energy barrier for the enzyme reaction is estimated at 24.5—31.6 kcal mol−1 (AMl/CHARMM), and 2.7—11.9 kcal mol−1 with corrections (e.g. B3LYP/6-31 + G(d)). In agreement with previous studies, the present analysis of the calculated paths provides unequivocal evidence of significant transition state stabilization by the enzyme, indicating that this is central to catalysis by the enzyme. The active site is exquisitely complementary to the transition state, stabilizing it more than the substrate, so reducing the barrier...
74 citations
TL;DR: NAC simulations suggests that the experimentally measured 100 fold tighter binding of TSA compared to CHOR does not originate from the difference between NAC and the TS binding affinities, but might be due to the free energy cost to bring the two carboxylates of CHOR together to interact with Arg28 and Arg11* at the active site.
Abstract: The Claisen rearrangements of chorismate (CHOR) in water and at the active site of E. coli chorismate mutase (EcCM) have been compared. From a total of 33 ns molecular dynamics simulation of chorismate in water solvent, seven diaxial conformers I-VII were identified. Most of the time (approximately 99%), the side chain carboxylate of the chorismate is positioned away from the ring due to the electrostatic repulsion from the carboxylate in the ring. Proximity of the two carboxylates, as seen in conformer I, is a requirement for the formation of a near attack conformer (NAC) that can proceed to the transition state (TS). In the EcCM.CHOR complex, the two carboxylates of CHOR are tightly held by Arg28 of one subunit and Arg11* of the other subunit, resulting in the side chain C16 being positioned adjacent to C5 with their motions restricted by van der Waals contacts with methyl groups of Val35 and Ile81. With the definition of NAC as the C5...C16 distance < or =3.7 A and the attack angle < or =30 degrees, it was estimated from our MD trajectories that the free energy of NAC formation is approximately 8.4 kcal/mol above the total ground state in water, whereas in the enzyme it is only 0.6 kcal/mol above the average of the Michaelis complex EcCM.CHOR. The experimentally measured difference in the activation free energies of the water and enzymatic reactions (Delta Delta G(++)) is 9 kcal/mol. It follows that the efficiency of formation of NAC (7.8 kcal/mol) at the active site provides approximately 90% of the kinetic advantage of the enzymatic reaction as compared to the water reaction. Comparison of the EcCM.TSA (transition state analogue) and EcCM.NAC simulations suggests that the experimentally measured 100 fold tighter binding of TSA compared to CHOR does not originate from the difference between NAC and the TS binding affinities, but might be due to the free energy cost to bring the two carboxylates of CHOR together to interact with Arg28 and Arg11* at the active site. The two carboxylates of TSA are fixed by a bicyclic structure. The remaining approximately 10% of Delta Delta G(++) may be attributed to a preferential interaction of Lys39-NH(3)(+) with O13 ether oxygen in the TS.
65 citations
TL;DR: There is no discernible transition-state stabilization in the CM reaction, and in anthropomorphic terms, each enzyme has had to do what it must to have a biologically relevant rate of reaction.
Abstract: Madicago sativa chalcone isomerase (CI) catalyzes the isomerization of chalcone to flavanone, whereas E coli chorismate mutase (CM) catalyzes the pericyclic rearrangement of chorismate to prephenate Covalent intermediates are not formed in either of the enzyme-catalyzed reactions, KM and kcat are virtually the same for both enzymes, and the rate constants (ko) for the noncatalyzed reactions in water are also the same This kinetic identity of both the enzymatic and the nonenzymatic reactions is not shared by a similarity in driving forces The efficiency (ΔGo⧧ − ΔGcat⧧) for the CI mechanism involves transition-state stabilization through general-acid catalysis and freeing of three water molecules trapped in the E·S species The contribution to lowering ΔGcat⧧ by an increase in near attack conformer (NAC) formation in E·S as compared to S in water is not so important In the CM reaction, the standard free energy for NAC formation in water is 84 kcal/mol as compared to 06 kcal/mol in E·S Because the va
63 citations
TL;DR: B3LYP/6-31G(d,p) calculations on reactants and transition states are shown to correctly predict the outcome of such aromatic Claisen rearrangements from either the preferential reactant ground-state conformation or the less energetic transition state, or both.
Abstract: Theoretical calculations and the isomeric product composition for a series of eight meta-substituted allyl aryl ethers confirm the reliability of a new (1)H NMR methodology used to predict aromatic Claisen regioselectivity from ground-state conformational preference of the reactant allyloxy group. Frontier HOMO-LUMO intramolecular orbital interactions, a classical approach in predicting reactivity and selectivity for Claisen rearrangements of allyl vinyl ethers, is shown to fail to mimic transition-state orbital interactions for aromatic Claisen rearrangements of meta-substituted allyl aryl ethers. B3LYP/6-31G(d,p) calculations on reactants and transition states are shown, however, to correctly predict the outcome of such aromatic Claisen rearrangements from either the preferential reactant ground-state conformation (theoretical predictions that agree with the NMR measurements) or the less energetic transition state, or both.
54 citations
TL;DR: The convergent total synthesis of (+)-okaramine J was achieved in a longest linear sequence of 12 steps from l-tryptophan tert-butyl ester in a key reaction was the acid-catalyzed room-temperature aza-Claisen rearrangement of a N-reverse-prenylated hexahydro[2,3-b]pyrroloindole to a C-preylated derivative.
TL;DR: In this article, a biomimetic Claisen/Diels-Alder/Claisen reaction cascade was used to synthesize forbesione and desoxymorellin.
Abstract: A concise synthesis of forbesione (1) and desoxymorellin (3) is presented. Central to the strategy is a biomimetic Claisen/Diels–Alder/Claisen reaction cascade that proceeds in a regioselective manner and produces the desired scaffold exclusively. The observed regioselectivity and product distribution of the Claisen/Diels–Alder/Claisen reaction are attributed to the electronic effects of the xanthone oxygen (O10), the C9 carbonyl group and the nature of the C1 functionality.
TL;DR: The preequilibrium free-energy differences between diaxial and diequatorial conformers of chorismate have been reframed using the near attack conformation (NAC) concept of Bruice and co-workers, and differences in free energies of activation for the two polar protic solvents and the gas phase were yielded.
Abstract: Solvent effects on the rate of the Claisen rearrangement of chorismate to prephenate have been examined in water and methanol. The preequilibrium free-energy differences between diaxial and diequatorial conformers of chorismate, which had previously been implicated as the sole basis for the observed 100-fold rate increase in water over methanol, have been reframed using the near attack conformation (NAC) concept of Bruice and co-workers. Using a combined QM/MM Monte Carlo/free-energy perturbation (MC/FEP) method, 82%, 57%, and 1% of chorismate conformers were found to be NAC structures (NACs) in water, methanol, and the gas phase, respectively. As a consequence, the conversion of non-NACs to NACs provides no free-energy contributions to the overall relative reaction rates in water versus methanol. Free-energy perturbation calculations yielded differences in free energies of activation for the two polar protic solvents and the gas phase. The rate enhancement in water over the gas phase arises from preferential hydration of the transition state (TS) relative to the reactants via increased hydrogen bonding and long-range electrostatic interactions, which accompany bringing the two negatively charged carboxylates into closer proximity. More specifically, there is an increase of 1.3 and 0.6 hydrogen bonds to the carboxylate groups and the ether oxygen, respectively, in going from the reactant to the TS in water. In methanol, the corresponding changes in hydrogen bonding with first shell solvent molecules are small; the rate enhancement arises primarily from the enhanced long-range interactions with solvent molecules. Thus, the reaction occurs faster in water than in methanol due to greater stabilization of the TS in water by specific interactions with first shell solvent molecules.
TL;DR: A new and efficient total synthesis of pseudophrynaminol, the pyrrolo[2,3-b]indole alkaloid bearing the allylic moiety at the 3a-position, has been achieved by a sequence involving 3-allylindol-2-one 8 as a key intermediate as mentioned in this paper.
TL;DR: In this article, a new cobaltocenyl oxazoline palladacycle compound was prepared for the enantioselective aza-Claisen rearrangement of allylic imidates.
Abstract: A new cobaltocenyl oxazoline palladacycle compound was prepared for the enantioselective aza-Claisen rearrangement of allylic imidates. Studies on the effect of face-blocking and the mechanism of the reaction were carried out.
TL;DR: In this paper, a synthesis of the alkylidene cyclopentenone prostaglandin TEI 9826 has been realized, using a stereoselective Claisen rearrangement from the allylic alcohol.
TL;DR: Kinetic isotope effects have been computed for the Claisen rearrangement of chorismate to prephenate in aqueous solution and in the active site of ch orismate mutase from B. subtilus, providing new information on an important enzymatic transformation and key factors responsible for the kinetics of its molecular mechanism are clarified.
Abstract: Kinetic isotope effects have been computed for the Claisen rearrangement of chorismate to prephenate in aqueous solution and in the active site of chorismate mutase from B. subtilus. These included primary 13C and 18O and secondary 3H effects for substitutions at the bond-making and bond-breaking positions. The initial structures of the putative stationary points on the potential energy surface, required for the calculations of isotope effects using the CAMVIB/CAMISO programs, have been selected from hybrid QM/MM molecular dynamical simulations using the DYNAMO program. Refinement of the reactant complex and transition-state structures has been carried out by means of AM1/CHARMM24/TIP3P calculations using the GRACE program, with full gradient relaxation of the position of > 5200 atoms for the enzymic simulations, and with a box containing 711 water molecules for the corresponding reaction in aqueous solution. Comparison of these results, and of gas phase calculations, with experimental data has shown that the chemical rearrangement is largely rate-determining for the enzyme mechanism. Inclusion of the chorismate conformational pre-equilibrium step in the modelled kinetic scheme leads to better agreement between recent experimental data and theoretical predictions. These results provide new information on an important enzymatic transformation, and the key factors responsible for the kinetics of its molecular mechanism are clarified. Treatment of the enzyme and/or solvent environment by means of a large and flexible model is absolutely essential for prediction of kinetic isotope effects.
TL;DR: In this paper, a number of 4-aryloxymethyl-7-chlorothiopyrano[2,3-b]thiochromen-5(2H)-ones were regioselectively synthesized in 80-85% yield by the Claisen rearrangement of 2-(4′-aryloxybut-2′-ynylmercapto)THIOchromen4-ones in refluxing chlorobenzene for 3 h.
TL;DR: In this article, a double Claisen rearrangement of a suitable 1,4-diallyloxyarene system followed by ring-closing metathesis of the resulting diene has been developed for the synthesis of various benzannulated cyclohexenes.
Abstract: A new route involving double Claisen rearrangement of a suitable 1,4-diallyloxyarene system followed by ring-closing metathesis of the resulting diene has been developed for the synthesis of various benzannulated cyclohexenes. An important demonstration of this methodology is the construction of the tetracyclic quinophenolic ring system of the clinically important anthracyclines.
TL;DR: The first synthesis of acyclic 2-(1,3-oxazolin-2-yl)-substituted allyl vinyl ethers was reported in this paper.
TL;DR: In this article, the authors describe the racemic and stereoselective synthetic route for a novel 6′(α)-hydroxy-carbovir from a simple acyclic precursor, Solketal.
TL;DR: A variety of β- or α-C-glycosides may be readily accessed in an entirely stereoselective fashion from esters derived from the reaction of carboxylic acids and 3-hydroxy glycals, by way of a tandem reaction sequence of Tebbe methylenation and Claisen rearrangement as discussed by the authors.
Abstract: A variety of β- or α-C-glycosides may be readily accessed in an entirely stereoselective fashion from esters derived from the reaction of carboxylic acids and 3-hydroxy glycals, by way of a tandem reaction sequence of Tebbe methylenation and Claisen rearrangement. Though of wide scope, for example allowing the synthesis of 1–6 linked C-disaccharides, the methodology does not currently allow the synthesis of C-glycosyl α-amino acids.
TL;DR: A new synthetic sequence involving the use of Ireland-Claisen rearrangement of propargylic acetates to form the corresponding benzannulated enyne-allenes followed by Schmittel cyclization to generate benzofulvene biradicals for radical cyclizations leading to polycyclic aromatic compounds was established.
Abstract: A new synthetic sequence involving the use of Ireland−Claisen rearrangement of propargylic acetates to form the corresponding benzannulated enyne-allenes followed by Schmittel cyclization to generate benzofulvene biradicals for radical cyclizations leading to polycyclic aromatic compounds was established. Treatment of 9-fluorenone (8) with the lithium acetylide 9 followed by acetic anhydride produced the propargylic acetate 10. A sequence of reactions occurred after 10 was converted to the corresponding silyl ketene acetal 11. An initial Ireland−Claisen rearrangement produced the benzannulated enyne-allene 12, which then underwent a Schmittel cyclization reaction to generate the benzofulvene biradical 13. A subsequent intramolecular radical−radical coupling then produced the formal Diels−Alder adduct 14, which in turn underwent a prototropic rearrangement to give the silyl ester 15 and, after hydrolysis, the carboxylic acid 16 in 57% overall yield from 10 in a single operation. An intramolecular acylation...
TL;DR: The Johnson-Claisen rearrangement of enantiopure allylic alcohols in triethylorthopropionate is the key step for the preparation of chiral molecules with benzylic stereogenic carbon atoms bearing an isopropyl moiety as mentioned in this paper.
Abstract: The Johnson–Claisen rearrangement of enantiopure allylic alcohols in triethylorthopropionate is the key step for the preparation of chiral molecules with benzylic stereogenic carbon atoms bearing an isopropyl moiety. The synthetic procedure is applied to the preparation of ( R )- and ( S )-3-methyl-2-phenylbutylamine.
TL;DR: In this paper, a variety of α-C-glycosides may be accessed in an entirely stereoselective fashion from 3-OH glycal esters, by way of the tandem reaction sequence of Tebbe methylenation and Claisen rearrangement.
TL;DR: In this paper, a tandem three stages process to a series of trifluoromethyl and halodifluorsimidyl 2,4-unsaturated ketones is described.
TL;DR: In this paper, the total synthesis of α-herbertenol, β-hernertenol and 1,13-herbertenediol, employing a Claisen rearrangement and ring-closing metathesis as key reactions for the generation of the cyclopentane containing vicinal quaternary carbons, has been described.
TL;DR: In this paper, a 2.2-Methylene-5-vinyl-tetrahydrofuran derivative was obtained from α-d -glucose.
Abstract: 2-Methylene-5-vinyl-tetrahydrofuran derivative 6 was obtained from α- d -glucose. Treatment of 6 with triisobutylaluminium (TIBAL) induced Claisen expansion reaction to give the seven-membered carbasugar derivative 7 , which represents a new type of chiral building blocks. The rearrangement reaction has been proved to be highly stereoselective.