Showing papers on "Claisen rearrangement published in 1996"

The Mechanism of the Claisen Rearrangement: Déjà Vu All Over Again

Abstract: The great baseball player Yogi Berra, who is quoted in the title, succinctly described what it meant to learn something that others had long ago appreciated. The mechanism by which the enzyme chorismate mutase accelerates the Claisen rearrangement of chorismic acid has for many years perplexed and intrigued chemists and biochemists. Yet classical effects of solvents and catalysts, which were largely ignored by the chemical community, not only provided important clues about the mechanism of the enzyme, but put the Claisen rearrangement in a new perspective. Whereas chorismic acid once seemed exceptional because it rearranged so rapidly under physiological conditions, it is now clear that even allyl vinyl ether rearranges at room temperature in aqueous solution. While the ability of the enzyme to accelerate the rearrangement of chorismate by a factor of 106 was once considered extraordinary, catalysis by trivalent aluminum compounds matches, and in some cases exceeds, those rate enhancements. Therefore, it really should not be surprising to learn that Nature has independently evolved several structurally distinct solutions to the design of enzyme catalysts for the rearrangement of chorismic acid.

Cyclopentannulation by an Iterative Process of Sequential Claisen Rearrangement and Enyne Radical Closure: Routes to Triquinane and Propellane Systems and Use in the Synthesis of (±)-Ceratopicanol

Abstract: Cycloalkenyl acetylenes 4, which are easily prepared from allylic alcohols by Claisen rearrangement and homologation (1 → 4), generally undergo radical cyclization (4 → 6) on treatment with stannyl radicals. The products (6) can themselves be converted into allylic alcohols, so that the annulation sequence can then be repeated. In certain cases enyne cyclization initiated by stannyl radicals does not work, but an alternative process (cf. Scheme 9) of epoxide opening with bis(cyclopentadienyl)titanium(III) chloride can then be used. Di- and triquinanes (Scheme 3) were made by the stannyl radical approach; the epoxide route was used to prepare a simple propellane (Scheme 4) and in a synthesis of (±)-ceratopicanol (Schemes 5 and 9).

Application of the Ester Enolate Claisen Rearrangement in the Synthesis of Amino Acids Containing Quaternary Carbon Centers.

Abstract: Ester enolate Claisen rearrangement of highly substituted amino acid allylic esters 4 allows for the synthesis of sterically demanding amino acids 5 with β-quaternary carbon centers. Because of enolate fixation by chelation, the rearrangement occurs in a highly diastereoselective fashion. The methodology is suitable not only for glycine derivatives but also for allylic esters of various amino acids. In this case amino acids with two vicinal quaternary carbon centers are created. With unsymmetrically substituted allylic esters like 4k−n the rearrangement proceeds with a high degree of diastereoselectivity.

Diastereoselective Zwitterionic Aza-Claisen Rearrangement: The Synthesis of Bicyclic Tetrahydrofurans and a Total Synthesis of (+)-Dihydrocanadensolide.

Abstract: The zwitterionic Claisen rearrangement of optically-active N-allyl pyrrolidines and various acid chlorides proceeds with high simple diastereoselection (internal asymmetric induction) and high 1,2-asymmetric induction, generating a new C−C bond adjacent to a chiral C−O function. The resulting γ,δ-unsaturated amides were cyclized to the corresponding optically active γ-butyrolactones, which are useful intermediates in natural product synthesis. On one hand, a diastereoselective iodocyclization of several lactones led to tetrahydrofurans with a substitution pattern representing a key intermediate of an oxa-prostaglandin synthesis. On the other, a one-pot procedure of a Swern oxidation and consecutive Grignard reaction of one γ-lactone allowed a diastereoselective chain elongation. The final oxidation/cyclization sequence completed a highly efficient synthesis of the (+)-dihydrocanadensolide or its C-3 epimer, respectively.

Furo-fused 2H-chromenes: synthesis and photochromic properties

Abstract: New photochromic chromenes annulated with a furan ring have been synthesized. Thus, suitable heterocyclic phenols react with different propargylic alcohols in acidic medium to give the corresponding ethers, which cyclize into benzopyrans by thermal Claisen rearrangement. This synthetic approach was found to lead to a mixture of linear and angular chromenes that is strictly related to the nature of the phenol. However, regiospecificity could be obtained by reacting β-phenylcinnamaldehyde, in refluxing aprotic nonpolar solvents, with titanium(IV) salts of the former phenols. Electrocyclization of intermediately generated o-quinoid structures occurs on the α position towards the heterocyclic junction. All compounds exhibit photochromic behavior at room temperature. Furo-fused benzopyrans are particularly interesting with respect to naphthopyran parents in view of the bathochromically shifted and broadened absorption spectra of photoinduced forms. This trend is confirmed by the spectral data of several hetero...

Stereoselective Synthesis of Unsaturated Polyhydroxylated Amino Acids via Ester Enolate Claisen Rearrangement

Abstract: Ester enolate Claisen rearrangement of chelated N-protected chiral allylic amino acid esters results in the formation of polyhydroxylated γ,δ-unsaturated amino acids in good yields and with a high degree of chirality transfer.

Asymmetric Synthesis of the Diterpenoid Marine Toxin (+)-Acetoxycrenulide

Abstract: An enantioselective route to the marine toxin (+)-acetoxycrenulide is described. The early stages of the synthesis feature the conversion of (R)-citronellol into a butenolide whose sole stereogenic center is provided by the terpenic alcohol. Three contiguous chiral carbon atoms are subsequently set in the requisite absolute configuration by conjugate addition of an enantiopure allylphosphonamide reagent. The resulting product is transformed during several steps into a primary selenoxide whose thermal activation in dimethylacetamide at 220 °C promotes sequential 1,2-elimination and Claisen rearrangement. The cyclooctenone core of the target is formed in this step. The final stages of the synthesis involve a series of fully stereoselective reactions including Simmons−Smith cyclopropanation and controlled Dibal-H reduction. The naturally occurring dextrorotatory enantiomer of acetoxycrenulide was ultimately acquired.

New developments of thiocarbonyl compounds and sulfines in organic synthesis

Abstract: The oxidation reaction of aliphatic thiocarbonyl compounds has been revisited in order to give access to the elusive corresponding suljines and to achieve thiophilic addition of nucleophiles. Various compounds (thioketones, dithioesters, thionesters, trithiocarbonates, trithioperesters) have been treated with a peroxycarboxylic acid. In all cases the corresponding sulfnes are formed, in contrast to literature expectations. Their behaviour towards nucleophiles has been investigated. The reaction with alkylithiums proved very useful: a clean and rapid thiophilic addition (no enethiolization) was observed at -78 “C. The resulting dithioacetal monoxides are easily transformed into carbonyl compounds (aldehydes, ketones) either by a simple mineral acid treatment or by a spontaneous rearrangement which takes place at ambient temperature. It provides a new formal entry to acyl anions Cformed by an addition reaction and not by deprotonation). A second illustration of the specijic properties of sulfur compounds is disclosed with a new asymmetric version of the Claisen rearrangement. Sulfur is used to facilitate the thermal course of the reaction and a sulfinyl adjacent group is introduced for diastereocontrol First examples show that this transposition indeed occurs at room temperature and with an excellent diastereomeric ratio (2 93:7). Sulfur plays a major role in heteroatom chemistry (1). We wish to report our recent results showing more applications to organic synthesis for the specific properties of some sulfur groups. Replacement of the oxygen of a carbonyl group by a sulfinyl group (using a sulfine) allows to reverse the polarity of the C=S moiety and the attack of a nucleophile takes place on sulfur rather than on carbon. TMoDhiIlc addNon

Diastereoselective Zwitterionic Aza‐Claisen Rearrangement: Synthesis of Nine‐Membered Ring Lactams and Transannular Ring Contraction

Abstract: The zwitterionic aza-Claisen rearrangement of optically active 3-pyrrolidine acryl esters and various acid chlorides to generate optically active azoninones proceeds with high simple diastereoselectivity (internal asymmetric induction) and a complete 1,3-chirality transfer. The reaction path observed depends on the subsitution pattern of the allylic system: while the more electron-rich alkylated allyl amine fromed predominantly von Braun type products, the α,β-unsaturated esters could be rearranged with high yields. The azoninones thus obtained were treated with electrophiles, inducing regio- and diastereoselective transannular ring contractions. The resulting indolizidinones should be useful key intermediates in alkaloid synthesis.

Synthesis ofγ,δ-unsaturated amino acids via ester enolate Claisen rearrangement of chelated allylic esters

Abstract: Deprotonation ofN-protected amino acid allylic esters with LDA at −78°C and subsequent addition of a metal salt presumably results in the formation of a chelated metal enolate which undergoes Claisen rearrangement upon warming up to room temperature, giving rise to unsaturated amino acid. Many different metal salts can be used for chelation, but in general the best results are obtained with zinc chloride. Due to the fixed enolate geometry, as a result of chelate formation, and a strong preference for thechair like transition state, the rearrangement proceeds with a high degree of diastereoselectivity. This methodology can be applied to acyclic as well as to cyclic substrates, and even to peptides, and allows for the synthesis of amino acids containing quaternary carbon centers.

Domino syntheses of five-, six- and seven-membered O-, N- and S-heterocycles from α-, β- and γ-substituted carboxylic esters

Abstract: By a one-pot procedure, tetronic acids, tetronates, coumarins, benzoxepinones and their N- and S-analogues are readily accessible from keteneylidene(triphenyl)phosphorane 2 and carboxylic esters bearing OH, NHR or SH groups in an α-, β- or γ-position by an addition/Wittig olefination/(Claisen rearrangement) sequence. This cascade can be controlled by temperature variation. Extension of this procedure by a further addition step yielding annulated bisheterocycles such as the furoquinolone 28 is possible in some cases.

An enantioselective synthesis of the strychnos alkaloid (-)-tubifoline

Abstract: An enantioselective synthesis of the Strychnos alkaloid (−)-tubifoline, involving the kinetic resolution of racemic 1-(3-pyridyl)ethanol, the orthoester Claisen rearrangement of the enantiopure allylic alcohol 5 , Smith indolization of the resulting 4-piperidineacetate 6 , photocyclization of chloroacetamide 9 , and final transannular cyclization, is reported.