Claisen Rearrangement Products Research Articles

Lewis Acid-Catalyzed Halonium Generation for Morpholine Synthesis and Claisen Rearrangement.

We disclose here practical strategies toward the synthesis of morpholines and Claisen rearrangement products based on the divergent reactivity of a common halonium intermediate. These reactions employ widely available alkenes in a Lewis acid-catalyzed halo-etherification process that can then transform them into the desired products with exceptional regioselectivity for both activated and unactivated olefins. Our mechanistic probe reveals an interesting regiochemical kinetic resolution process.

Copper-Catalyzed Reductive Ireland-Claisen Rearrangements of Propargylic Acrylates and Allylic Allenoates.

The copper-catalyzed reductive Ireland-Claisen rearrangement of propargylic acrylates led to 3,4-allenoic acids. The use of silanes or pinacolborane as stoichiometric reducing agents and triethylphosphite as a ligand facilitated the divergent and complementary selectivity for the synthesis of diastereomeric anti- and syn-rearranged products, respectively. Copper-catalyzed reductive Ireland-Claisen rearrangement of allylic 2,3-allenoates proceeded effectively only when pinacolborane was used as a reductant to generate various 1,5-dienes in excellent yields and with good diastereoselectivities in some cases. Mechanistic studies showed that the silyl and boron enolates, rather than the copper enolate, underwent a stereospecific rearrangement via a chairlike transition state to afford the corresponding Claisen rearrangement products.

Computational and Further Experimental Explorations of the Competing Cascades Following Claisen Rearrangements of Aryl Propargyl Ethers: Substituent Effects on Reactivity and Regioselectivity.

We report a computational investigation of two reaction cascades occurring following the Claisen rearrangements of aryl propargyl ethers to the alternate ortho positions in unsymmetrical reactants. Our computations explain how substituents influence reactivity and regioselectivity. Rearrangement to the substituted ortho carbon leads to a tricyclo[3.2.1.0]octane core, while rearrangement to an unsubstituted ortho carbon leads to a benzopyran. Density functional theory with ωB97X-D indicates that these reactions involve rate-determining Claisen rearrangements followed by subsequent reaction cascades of the Claisen rearrangement products depending on the presence or absence of a substituent at the ortho carbon.

Concise Total Syntheses of (±)-Joubertiamine, (±)-O-Methyl­joubertiamine, (±)-3′-Methoxy-4′-O-methyljoubertiamine, (±)-Mesembrane, and (±)-Crinane

A method to access <i>cis</i>-3a-aryloctahydroindole alkaloids has been developed through a key strategy involving Eschenmoser–Claisen rearrangement of allylalcohol. This approach gives us an opportunity to access the all-carbon quaternary center required for <i>cis</i>-3a-aryloctahydroindole alkaloids. Subsequent simple allylic oxidation of Eschenmoser–Claisen products and synthetic elaborations (reductions/oxidations) enabled the total syntheses of the title compounds to be completed in good yields in a few steps. The strategic viability was further tested in the total syntheses of <i>Amaryllidaceae</i> alkaloids (±)-mesembrane and (±)-crinane. Towards this end, we synthesized advanced intermediate keto-aldehydes from Eschenmoser–Claisen rearrangement products through iodolactonization followed by elaboration involving reduction and oxidation steps.

Stereocontrolled Total Synthesis of (+)‐trans‐Dihydronarciclasine

A highly stereoselective and efficient total synthesis of trans-dihydronarciclasine from a readily available chiral starting material was developed. The synthesis defines two of the five stereogenic centers of the natural product by an amino acid ester-enolate Claisen rearrangement. The other three stereogenic centers are created in a highly stereocontrolled fashion via a six-ring vinylogous ester intermediate, which is generated from the γ,δ-unsaturated ester functional group of the Claisen rearrangement product in an efficient three-step sequence. This concise total synthesis exemplifies the use of a highly regioselective Friedel-Crafts-type cyclization to form the B ring via an isocyanate intermediate derived from an N-Boc group, which is superior to the conventional method using an imino triflate intermediate. This same N-Boc group is employed to give high selectivity in the Claisen rearrangement earlier in the sequence.

Claisen Rearrangement of Carbohydrate‐Derived Precursors Towards Highly Functionalized Cyclooctenones with L‐xylo, D‐arabino and L‐lyxo Configuration and Their Diastereoselective Transformations

AbstractD‐Glucose and D‐mannose have been transformed into precursors incorporating allyl vinyl ether substructures. Both thermally and catalytically, these cyclic allyl vinyl ethers could be converted into the corresponding Claisen rearrangement products. The conformations of these enantiopure 5‐cyclooctenones were studied by NMR spectroscopy and X‐ray crystallography. They proved to be versatile substrates for highly stereo‐ and regioselective modifications. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)

Reaction of Orthoesters with Alcohols in the Presence of Acidic Catalysts: A Study.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Catalytic Diastereo‐ and Enantioselective Claisen Rearrangement of 2‐Alkoxycarbonyl‐Substituted Allyl Vinyl Ether

AbstractThe catalytic asymmetric Claisen rearrangement of 2‐alkoxycarbonyl‐substituted allyl vinyl ethers that contain two stereogenic double bonds is described. A combination of the highly Lewis acidic [Cu{(S,S)‐tert‐Bu‐box}](H2O)2(SbF6)2 complex and molecular sieves served as catalyst and afforded the Claisen rearrangement products, substituted and functionalized α‐keto esters, in high yield with a remarkable diastereo‐ and enantioselectivity. The influence of ligand structure, counterion and allyl vinyl ether double bond configuration on the stereoselectivity of the rearrangement was briefly investigated. We propose an explanation for the rate accelerating effect of the Lewis acid as well as a stereochemical model which serve to explain and predict the stereochemical course of the copper bis(oxazoline) catalyzed Claisen rearrangement.

Conformational Study of Isobutenylene Chains in Tandem Claisen Rearrangement Products. Insights from X-ray Crystallography and 1H NMR for Salicylideneaniline Derivatives

Abstract A new variety of salicylideneaniline derivatives were prepared from a substituted aniline and a bis(hydroxybenzaldehyde) which has been synthesized through a tandem Claisen rearrangement reaction. X-ray crystal structures were obtained for many of the products. With respect to the conformation of their isobutenylene chain, the crystal structures can be classified into three groups: i.e., skew–skew (I), syn–skew (II), and syn–syn (III) conformers. The 1H NMR spectra were significantly different among these compounds, especially for the isobutenylene moiety. The set of the chemical shifts, (δ (Ha), δ (Hb)), of exo-methylene (Ha) and benzylic methylene (Hb) is a good index for classifying the NMR spectra, and these values also reflect the conformation of the isobutenylene chain found in the crystal state. Namely, each conformer of I, II, and III corresponds to the (δ (Ha), δ (Hb)) values (ppm) around (5.10, 3.43), (4.86, 3.43), and (4.74, 3.56), respectively. This result is verified by the complexation study of a 15-crown-5 derivative with alkali metal ions. The chemical shift change caused by the complexation is successfully explained by the conformation changes among I, II, and III.

Johnson orthoester Claisen rearrangement products of some (1-oxa-4-thiaspiro[4.5]dec-6-en-6-yl)alkanols.

The crystal structures of two 1-oxa-4-thiaspiro[4.5]decane derivatives, ethyl 6-benzylidene-1-oxa-4-thiaspiro[4.5]decane-7-acetate, C19H24O3S, and (6-ethylidene-1-oxa-4-thiaspiro[4.5]decan-7-yl)ethyl 4-bromobenzoate, C19H23BrO3S, obtained under Johnson orthoester Claisen rearrangement conditions, exhibit different olefin geometry. Both structures are composed of independent molecules separated by normal van der Waals distances. The S-Csp(3) bond distances are significantly different from each other, as has been observed in similar structures; the remaining molecular dimensions are as expected.

Stereoselective carbon–carbon bond forming reactions of chiral cyclopent-2-enone and cyclopentene-1-methanol, both spiro-connecting a 1,2:5,6-di- O-isopropylidene-α- d-glucofuranosyl ring

The conjugate additions of a variety of organocopper reagents or dimethyl malonate anion to a spirocyclic cyclopent-2-enone connecting a 1,2:5,6-di- O-isopropylidene-α- d-glucofuranosyl ring as a constituent of the spiro structure, namely (1 S,3 R,4 R,5 R)-3,4-(isopropylidenedioxy)-1-[(1 R)-1,2-(isopropylidenedioxy)ethyl]-2-oxa-spiro[4.4]non-6-en-8-one, proceeded stereoselectively in some cases affording a variety of β-functionalized cyclopentanone derivatives. The thermal treatment of (1 S,3 R,4 R,5 R)-7-(hydroxymethyl)-3,4-(isopropylidenedioxy)-1-[(1 R)-1,2-(isopropylidenedioxy)ethyl]-2-oxaspiro[4.4]non-6-ene, another d-glucose-derived spirocyclic substrate, with triethyl orthoacetate in the presence of a catalytic amount of acid afforded the Claisen rearrangement product with a high level of diastereoselectivity.

Claisen rearrangement of allyl phenyl ether and its sulfur and selenium analogues on electron impact

The electron impact (EI) mass spectrum of allyl phenyl ether (1) includes an ion at m/z 106 that is formed mainly by the loss of CO from the molecular ion, as supported by high resolution and MS/MS data. The formation of the [M - CO](+) ion from 1 can be explained in terms of the Claisen rearrangement of 1 after ionization in the ion source of the mass spectrometer. Similarly, allyl phenyl sulfide (2) and allyl phenyl selenide (3) showed characteristic ions corresponding to [M - CH(3)](+), [M - XH](+) (X = S or Se) and [M - C(2)H(4)](+.), and the formation of these ions are explained via Claisen rearrangement of 2 and 3 in the ion source of the mass spectrometer resulting in a mixture of rearrangement products. The formation of molecular ions of 2-allyl thiophenol and 2-allyl selenophenol as intermediates, that cannot be isolated as the neutrals from the solution phase Claisen rearrangement of 2 and 3, respectively, is clearly indicated in the gas phase. The mass spectra of the rearrangement products obtained from the solution phase reaction were also consistent with the proposal of formation of these products in the ion source of the mass spectrometer. The formation of characteristic fragment ions attributed to the Claisen rearrangement products are also evident in the collision induced dissociation spectra of the corresponding molecular ions. Copyright 2000 John Wiley & Sons, Ltd.

A chiral cyclohex-2-enone carrying a hexofuranosyl substituent which directs highly stereoselective 1,4-conjugate additions

The reaction of ( Z)-3-deoxy-3- C-[(hydroxymethyl)methylene]-1,2:5,6-di- O-isopropylidene-α-D- ribo-hexo-furanose, prepared from D-glucose, with 1,1-dimethoxycyclohexane in the presence of propanoic acid at 135°C, then at 200°C, provided two Claisen rearrangement products, namely (2 R,3 R,4 S,5 S)-2,3-(isopropylidene)dioxy-5-[(1 R)-1,2-(isopropylidene)dioxyethyl]-4-[(1 S)- and (1 R)-2-oxocyclohexyl]-4-vinyltetrahydrofuran in a ratio of 3.3:1. L-Selectride ® reduction of the major product gave the corresponding ( S)-cyclohexanol exclusively. In contrast, the Claisen rearrangement of the aforementioned allylic alcohol with 3,3-dimethoxycyclohexene proceeded with complete stereoselectivity to provide the corresponding 4-[(1 S)-2-oxocyclohex-3-enyl]-4-vinyltetrahydrofuran exclusively. The 1,4-conjugate additions to the thus formed cyclohexenone derivative with dimethyl and divinylcuprates proceeded with complete π-facial selection to provide the 3-methylated and 3-vinylated cyclohexanone derivatives, both in high yields.

Enantioselective aromatic Claisen rearrangement

The development of a highly enantioselective aromatic Claisen rearrangement was achieved by the reaction of catechol mono allylic ethers with chiral boron reagent 1. This system was also shown to avoid the formation of para rearrangement and abnormal Claisen rearrangement products.

Claisen Rearrangement of 4-Allyloxytropones and Cerium(IV) Ammonium Nitrate-Oxidation of 4-Hydroxytropones

Abstract Heating 4-allyloxytropones gave Claisen rearrangement products together with oxidation products such as C–C coupling dimers. The products were sensitive to oxygen. Some of the dimeric products were obtained from the cerium(IV) ammonium nitrate-oxidation of 4-hydroxytropones.

Use of 1,1,1,3,3,3-hexamethyldisilazane and N,O-bis-(trimethylsilyl)acetamide in aromatic Claisen rearrangement: An efficient method for preventing abnormal Claisen rearrangement

Both 1,1,1,3,3,3-hexamethyldisilazane and N,O-bis-(trimethylsilyl)acetamide have been shown to suppress the formation of abnormal aromatic Claisen rearrangement products by efficiently trapping the incipient normal products as their silyl ethers under mild conditions.

Synthetic route to 4‐(2‐aminoethyl)‐5‐hydroxyindole derivatives

AbstractIn synthetic studies leading to the title compounds, application of the Claisen rearrangement of 5‐allyloxyindole was investigated. Almost quantitative yields of Claisen rearrangement product were realized, and a strategy for oxidative cleavage of the allyl double bond to an indole‐4‐acetaldehyde derivative was developed. A new method for conversion of 2,3‐dihydroindoles into indoles was utilized: air oxidation in a strongly basic environment. The Claisen rearrangement of allyloxyindoles is presented as a method having considerable potential utility in synthesis of a variety of polysubstituted indoles.

Chiral 2,2-disubstituted cyclohexanones; annulation via Claisen rearrangement products

The methyl enol ether of 2-methylcyclohexanone reacts regiospecifically with the optically active forms of but-3-yn-2-ol and but-3-en-2-ol. (R)-But-3-yn-2-ol yields an approximately 4 : 1 mixture of (R)-2-methyl-2-(R-buta-1,2-dienyl)cyclohexanone and the corresponding SR compound. By contrast the but-3-en-2-ol reaction is ca. 96% enantioselective; (R)-but-3-en-2-ol gives (R)-2-(trans-but-2-enyl)-2-methylcyclohexanone and (S)-but-3-en-2-ol gives the corresponding (S)-cyclohexanone. These Claisen rearrangement products have been transformed into Robinson-type annulated ketones. Cleavage of some highly hindered esters has been carried out efficiently by sodium methylsulphinyl-methanide in dimethyl sulphoxide.

The preparation and thermolysis reactions of allyl 3,4,5,6,7,8- hexafluoroquinolin-2-yl ether, allyl 2,3,5,6,7,8- hexafluoroquinolin-4-yl ether and allyl 3,4,5,6,7,8- hexafluoroisoquinolin-1-yl ether.

Sodium allyl oxide reacted with 2,3,4,5,6,7,8-heptafluoroquinoline to give allyl 3,4,5,6,7,8-hexafluoroquinolin-2-yl ether (7) and allyl 2,3,5,6,7,8-hexafluoroquinolin-4-yl ether (8) in the ratio 3.4:1 respectively, and with 1,3,4,5,6,7,8-heptafluoroisoquinoline to give allyl 3,4,5,6,7,8-hexafluoroisoquinolin- 1- yl ether (9). Thermolyses of (7) and (9) in tetralin at 212°C gave the Claisen rearrangement products (10) and (12) in which nitrogen is the migration terminus, in slow reactions over 48 h, whereas the isomerisation of (8) to (11) in which carbon is the migration terminus, was complete within 2.5 h at 147.5°C. Compound (11) is very susceptible to hydrolysis, giving with undried toluene, the dione (13) containing half a molecule of solvent toluene.

Partially fluorinated heterocyclic compounds. Part 23 [1]. Thermolysis reactions of 1,3,4,5,6,7,8-heptafluoro-2-naphthyl prop-2-enyl sulphide and 1,3,4,5,7,8-hexafluoro-2,6-di(prop-2-enylthio)naphthalene in NN-diethyl-aniline and related reactions with 1,3,4,5,6,7,8-heptafluoro-1-(prop-2-enyl)-naphthalen-2-one and 2,3,4,5,6-pentafluoro-4-(prop-2-enyl)2,5-cyclohexadienone

1,3,4,5,6,7,8-Heptafluoro-2-naphthyl prop-2-enyl sulphide (6) and 1,3,4,5,7,8-hexafluoro-2,6-di(prop-2-enylthio)naphthalene (7) were synthesised from octafluoronaphthalene. Compound (6) on heating with NN- diethylaniline (DEA) under reflux gave 4,5,6,7,8,9-hexafluoro-2,3-dihydro- 2-methylnaphtho[2,1-b]thiophen (8) and a small amount of 5,6,7,8,9,10-hexafluoro- 3,4-dihydro-2 H-naphtho[2,1-b]thiopyran (9); under the same conditions compound (7) gave 4,5,9,10-tetrafluoro-2,3,7,8-tetrahydro-2,7- dimethylnaphtho[2,1-b:6,5-b′]dithiophen (10) and a small amount of 4,5,10,11- tetrafluoro-2,3,8,9-tetrahydro-2-methyl-7 H-thieno[3′,2′:5,6]naphtho[2,1-b]- thiopyran (11). 1,3,4,5,6,7,8-Heptafluoro-1-(prop-2-enyl)naphthalen-2-one (4) in refluxing DEA gave 3,4,5,6,7,8-hexafluoro-1-(prop-2-enyl)-2-naphthol (13) and 4,5,6,7,8,9-hexafluoro-2,3-dihydro-2-methylnaphtho[2,1-b]furan (12); (13) is an intermediate in the formation of (12) from (4). 2,3,4,5,6- Pentafluoro-4-(prop-2-enyl)-2,5-cyclohexadienone (5) in refluxing DEA gave 2,3,5,6-tetrafluoro-4-(prop-2-enyl)phenol (14). The solvent DEA forms blood-red solutions with (4) and (5) indicative of an electron transfer process; it is proposed that the solvent causes the reduction of the carbonyl or thiocarbonyl group in the Claisen rearrangement products, followed by dehydrofluorination prior to cyclisation reactions taking place.