Ester Migration Research Articles

ChemInform Abstract: Radical 5‐exo Cyclization of Alkynoates with 2‐Oxoacetic Acids for Synthesis of 3‐Acylcoumarins.

AbstractThe protocol represents the first example for coumarin synthesis from alkynoates through decarboxylative radical 5‐exo annulation and ester migration.

Rh2(II)-catalyzed ester migration to afford 3H-indoles from trisubstituted styryl azides.

Rh2(II)-complexes trigger the formation of 3H-indoles from ortho-alkenyl substituted aryl azides. This reaction occurs through a 4π-electron-5-atom electrocyclization of the rhodium N-aryl nitrene followed by a [1,2]-migration to afford only 3H-indoles. The selectivity of the migration is dependent on the identity of the β-styryl substituent.

Radical 5-exo cyclization of alkynoates with 2-oxoacetic acids for synthesis of 3-acylcoumarins

A silver-promoted decarboxylative annulation of alkynoates with 2-oxoacetic acids leading to the formation of 3-acyl-4-arylcoumarins is reported. The process involves radical decarboxylative acylation, 5-exocyclization, and ester migration.

ChemInform Abstract: PtCl2‐Catalyzed Tandem Enyne Cyclization/1,2 Ester Migration Reaction Controlled by Substituent Effects of All‐Carbon 1,6‐Enynyl Esters.

On the move: A novel PtCl2-catalyzed tandem 1,6-enyne cyclization/1,2-acyloxy migration reaction was developed, which was shown to be controlled by substitution effects. Using this method, a series of substituted enol esters containing the cyclopentenyl motif were prepared in moderate to high yields.

ChemInform Abstract: Unexpected O‐Alkylation and Ester Migration in Phenolic 2,3‐Diaryl‐2,3‐dihydrobenzo[b]furans.

AbstractAttempted O‐alkylation of benzodihydrofuran derivative (I) proceeds through an unexpected hydrolysis of the nitrobenzoate esters accompanied by transfer of a ‐Pnb group to the aromatic 5‐OH and double alkylation of the newly generated 3,5‐dihydroxyphenyl moiety.

PtCl2‐Catalyzed Tandem Enyne Cyclization/1,2 Ester Migration Reaction Controlled by Substituent Effects of All‐Carbon 1,6‐Enynyl Esters

On the move: A novel PtCl2-catalyzed tandem 1,6-enyne cyclization/1,2-acyloxy migration reaction was developed, which was shown to be controlled by substitution effects. Using this method, a series of substituted enol esters containing the cyclopentenyl motif were prepared in moderate to high yields.

Unexpected O-alkylation and ester migration in phenolic 2,3-diaryl-2,3-dihydrobenzo[b]furans

O-alkylation of 2-(4-methoxyphenyl)-5-hydroxy-3-[1,3-phenylene-bis(4-nitrobenzoate)]-2,3-dihydrobenzo[b]furan results in the unexpected hydrolysis of the nitrobenzoate esters, transfer of a 4-nitrobenzoic acid group to the 5-hydroxyl group and double alkylation of the newly formed 3,5-diphenol moiety. A range of alkyl halides can be used and give access to O-alkyl analogues of ε-viniferin.

Mantyl tagged oligo α (1 → 2) mannosides as Candida albicans β-mannosyl transferases substrates: a comparison between synthetic strategies

Fluorescent oligomannosides are important tools for the evaluation of mannosyl transferase activities and selectivities. In a project dealing with Candida albicans β-mannosyl transferases, three mantyl tagged α (1 → 2) oligomannosides were prepared by different ways: using all ester strategy compatible with the presence of an azido group suitable for direct click chemistry; and alternatively using the more classic benzyl protecting groups. Although more elegant, the all ester strategy has shown important limitations: reduced reactivity of mannosyl donors, and 3 → 2 ester migration. Preliminary enzymatic studies have shown that the synthetic oligomannosides are efficient substrate of β-mannosyl transferases.

Synthesis and Properties of a Photoactivatable Analogue of Psychosine (β‐Galactosylsphingosine)

Synthesis and Properties of a Photoactivatable Analogue of Psychosine (β‐Galactosylsphingosine)

Efficient syntheses of calix[4]arenes in the 1,2-alternate conformation via intramolecular benzoate ester migrations

A previously known imidazole-initiated intramolecular ester migration was modified by replacing the imidazole with Cs 2CO 3 to effect the efficient conversion of 25, 27-bis- p-methoxy-, 25,27-bis- p-fluoro and 25, 27-bisbenzoyloxycalix[4]arene in the flattened cone conformation to the corresponding 25,26-benzoyloxy compounds in the 1,2-alt. The rearrangement was highly efficient for the unsubstituted and methoxy-substituted esters; the 1,2-alternate isomers were isolated in 80–88% yield, but less efficient for the fluoro-substituted ester (isolated yield 58%). The p-methoxy- and p-fluoroesters were further functionalized in subsequent alkylation reactions with methyl p-toluenesulfonate and pentaethyleneglycol-di- p-tosylate to produce dimethoxy- and calixcrown-ester derivatives in the 1,2-alt. in moderate to good yields. The high yields of the 1,2-alt. are attributed to a π-metal template effect involving the soft cesium ion from the base, two aryl rings and the two phenolate oxygens of the deprotonated calixarene.

Synthesis, Conformational Analysis, and Phase Characterization of a Versatile Self-Assembling Monoglucosyl Diacylglycerol Analog

Glycosyl diacylglycerols are excellent lipids for the formation of both bi- and monolayer lamellar systems but they are generally not commercially available, and the synthesis of optically pure glycosyl diacylglycerols inevitably involves protection and deprotection of glycerol linkers. A novel glycolipid designed to be an easily accessible structural surrogate of monoglucosyl diacylglycerol (MGDG) has been synthesized. In this molecule, glycerol is replaced with (S)-1,2,4-trihydroxybutane. Instead of the fatty acyl moieties found in MGDG, a 2,2-dialkyl-1,3-dioxolane function provides the hydrophobic moiety of the molecule. This different functionality affords chemically and physically tunable new properties in a glycolipid. These include base stability, increased mobility of the headgroup, possibilities of new packing arrangements, and the potential for use in encapsulation strategies using liposomes where a decrease in pH is used as the environmental cue for release. The acetal linkage also makes the molecule unsusceptible to degradation by phospholipase A and other esterase activities found in biological systems thus further extending their utility. The choice of the butane triol linker removes the common problem of racemization of protected glycerol by acetal and ester migration. It also affords synthetic simplicity since only one dioxolane acetal is formed on reaction of butane-1,2,4-triol with ketones, whereas in the case of glycerol, one hydroxyl group has to be selectively protected to avoid the formation of both enantiomers. 2-D NMR homonuclear and heteronuclear correlation spectroscopy together with nuclear Overhauser effect experiments and molecular mechanics calculation were used to obtain information on the headgroup orientation and on the configuration of the trialkoxybutane backbone. These supported a structure in which the alkyl chains were extended in a parallel fashion and the headgroup, although free to rotate along C2−C3 and C3−C4 of the trialkoxybutane substructure, extended away in the other direction in a manner similar to that observed in the case of MGDG. X-ray powder diffraction and optical microscopy data both supported a lamellar phase behavior of this amphiphilic molecule in water. 1H NMR experiments monitoring the rate of acetal cleavage of this amphiphile revealed its tunable acid susceptibility. The unique structural feature, phase behavior, and controllable acid susceptibility of this glycolipid is potentially useful in many applications.

Novel [1, N]-Carbon to Carbon Rearrangement of an Ester Group via Organotitanium Intermediates Wherein the N Varies from 2 to 5. Full Scope and Limitation Leading Predominantly to the Rearrangement

Abstract Malonates and methanetricarboxylates having an unsaturated side chain such as 2, 12, 20, 22, 24, 31, or 37 underwent a new ester rearrangement reaction promoted by (η2-propene)Ti(O-i-Pr)2 to afford the succinate derivative 4 or α,β-unsaturated ester 17, 21, 23, 25, 34, or 38 via the migration of the ester group from its original bis- or tris-ester position to the acetylene- or olefin-titanium complex. It has been found that the side reactions competing with the desired migration are dealkylation of the side chain of the ester and a simple cyclization. The substrates and conditions which allow the ester migration a preferential path were determined as well as the scope and limitation of this reaction.

Small Rings, 76[1]. – Intermediates on the Way to Tetramethyl Cyclopentadienonetetracarboxylate

Abstract„Potassium salt”︁ 6, already described by Cookson, reacts with suitable electrophilic reagents to yield the enol esters 8–10. A base‐catalyzed acylation of the hydroxy group in 8–10 cannot be achieved because deprotonation is immediately followed by a [1,5] ester migration. The same reaction occurs upon heating 8–10 to 80°C, leading to the 1,3‐keto enols 11, 12, and 14. Upon treatment of „alcohol”︁ 7 with acetyl chloride only the dimer 3 of cyclopentadienone 2 can be isolated.

Novel types of acyclic C-nucleoside analogues via the reaction of hydrogen bromide in acetic acid with l- threo-(glycerol-l-yl)pyrazolinediones

The reaction of hydrogen bromide in acetic acid with a number of l- threo-glycerolylpyrazolinediones and their partially acetalated, acetylated, benzoylated, and p-toluenesulfonylated derivatives has been investigated. The presence of an O-isopropylidene ring at the C-1 and C-2 positions and/or an acetyl group at position C-3 does not affect the mode of the reaction. The products are 1,3-dibromo-1,3-dideoxy-2- O-acetyl- l- erythro-glycerolyl derivatives, which are identical with those obtained from the corresponding triol precursor. The conditions of the reaction promote ester migration via the apparent formation of a dioxolanylium ion. However, ester migration was not observed in the corresponding 3-benzoate and 3-( p-toluenesulfonate), whereby 1-bromo-1-deoxy derivatives having the l- erythro configuration were obtained. The reaction of 6-bromo-6-deoxy-dehydro- l-ascorbic acid with phenylhydrazine gave a mixture of the corresponding bis(phenylhydrazone) and the 3-bromo-3-deoxy glycerolyl derivative of the pyrazolinedione.

The complete structure of the trifoliin a lectin-binding capsular polysaccharide of Rhizobium trifolii 843

The complete structure of the acidic, extracellular, capsular polysaccharide of Rhizobium trifolii 843 has been elucidated by a combination of chemical, enzymic, and spectroscopic methods, confirming an earlier proposed sugar sequence and assigning the locations of the acyl substituents. The polysaccharide was depolymerized by a lyase into octasaccharide units which were uniform in carbohydrate composition and linkage. These units also contained a uniform distribution of acetyl and pyruvic acetal [ O-(1-carboxyethylidene)] groups, and half of them were further acylated with d-3-hydroxybutanoyl groups. A much smaller proportion (<5%) of the oligomers was further acylated by a second d-3-hydroxy-butanoyl group. The locations of the substituents were determined chemically and by J-correlated, 1H-n.m.r. spectroscopy, proton nuclear Overhauser effect (n.O.e.)_ measurements, doubie-resonance 1H-n.m.r. spectroscopy, and 13C-n.m.r. spectroscopy. The composition and structure of the carbohydrate chain were determined by methylation analysis using g.l.c.-m.s. fast-atom-bombardment mass spectrometry, and n.m.r. studies on the reduced, deacylated oligomer. Structural studies were supplemented by n.m.r. analyses on the original polymer. The oligosaccharides were found to be branched octasaccharides with four sugar residues in each branch, and the carbohydrate sequence agreed well with that expected from earlier work. In the abbreviated sequence and structure ( 1a), the sugar residues are labelled “ a” through “ h”. The main chain ( a–d) is composed of a 4-deoxy-α- l- threo-hex-4-enopyranosyluronic acid group ( a) that is linked to O-4 of a 3- O-acetyl- d-glucosyluronic acid residue ( b) which is β-linked to O-4 of a d-glucosyl residue ( c). Residue c is β-linked to O-4 of the branching d-linked to O-4 of a d-glucosyl residue ( d). The side chain consists of a substituted d-galactosyl group ( h) which is β-linked to O-3 of residue 9 of a β-(1→4)-linked d-glucose trisaccharide (fragment e–f–g). The reducing end of the resulting tetrasaccharide ( e–f–g–h) is β-linked to O-6 of the branching d-glucose residue ( d). In the native polymer, this branching residue is α-linked to O-4 of the modified d-glucuronic acid residue ( a) which is the unsaturated sugar in the oligomer. A small proportion of the O-2 atoms of the acetylated d-glucosyluronic acid residues is acetylated because of ester migration. The two terminal sugars ( g and h) of the branch chain bear 4,6- O-(1-carboxyethylidene) groups. The d-galactosyl groups of half of the oligomers are acylated by d-3-hydroxybutanoyl groups at O-3. About 5% of the oligomers bear a second d-3-hydroxybutanoyl group at O-2 of the d-galactosyl group ( h).

A novel oxygen-to-carbon ester migration catalysed by 4-(N,N-dimethylamino)-pyridine in the benzofuranone ring system

4-(N,N-Dimethylamino)pyridine (DMAP) promotes the quantitative rearrangement of benzofuranone-derived enol carbonates to the corresponding carbon-acylated isomers.

A MIMIC STUDY ON COENZYME-B12 USING ORGANOCOBALOXIMES, THE REARRANGEMENT OF 1-SUBSTITUTED-2-OXOCYCLOPENTYLMETHYL RADICAL

Abstract The radical cleavage of the carbon-cobalt bond of 1-phenyl-2-oxocyclopentylmethyl cobaloxime (1) and 1-ethoxycarbonyl-2-oxocyclopentylmethyl cobaloxime (2) gave only 3-phenylcyclohex-2-enone (7) and 3-ethoxycarbonylcyclohex-2-enone (8), respectively, by acyl migration. This rearrangement may be a reasonable mimicry of the ester migration mediated by coenzyme-B12.

Selective tritylation and mesitylenesulphonylation of raffinose

Raffinose reacted with 3 molar equivalents of trityl chloride in pyridine to give a complex mixture of products from which 1′,6′,6″-tri- O-tritylraffinose 1 1 The unprimed, single-primed, and double-primed numbers refer to the carbon atoms in the d-glucosyl, d-fructosyl, and d-galactosyl rings, respectively. was isolated (20%) after chromatography, and characterised as the crystalline octa-acetate and octabenzoate. The octabenzoate was detritylated in methanolic 1% hydrogen chloride, without significant ester migration, to give the 1′,6′,6″-triol octabenzoate, from which 1′,6′,6″-trisulphonates were obtainable in high yields. Treatment of raffinose with 3 molar equivalents of mesitylenesulphonyl chloride in pyridine gave 1′,6′,6″-tri- O-mesitylenesulphonylraffinose (20%, after chromatography).

An ester migration in the rearrangement of a diels–alder adduct of a furan and a phenyl migration in the rearrangement of methyl 3,3,5-triphenylpyrazole-4-carboxylate

Methyl 5-methoxyfuran-2-carboxylate reacts with dimethyl acetylenedicarboxylate to give trimethyl 3-hydroxy-6-methoxybenzene-1,2,4-tricarboxylate, identified from its spectra and its conversion into diethyl 2,5-dihydroxyterephthalate. The thermal rearrangement of methyl 3,3,5-triphenyl-3H-pyrazole-4-carboxylate proceeds by a phenyl, and not by an ester, migration.

Hydrolysis of lecithins by venom phospholipase A I. Structure of the enzymically formed lysolecithins

Rat-liver [ 32P]lecithin was hydrolyzed by snake venom phospholipase A to give quantitative yield of [ 32P]lysolecithins. The lysolecithins were oxidized in buffered aqueous solutions in the pH range 2.8 to 7.0, with bromine or permanganate to yield a keto-lysolecithin derivative. The extent and rate of oxidation is pH dependent. Bromine oxidation is more rapid at pH 6.8 than at pH 5.5 or 2.8. Permanganate oxidation is rapid at pH 5.5 but very slow at pH 6.8. During the oxidation partial concomitant hydrolysis occurs. The keto-lysolecithin can be separated and measured by paper chromatography and thus permits the determination of the α-lysolecithin isomer. The amount of this isomer was found to vary between 54–94% depending on the pH at which the bromine oxidation is carried out. Definitive evidence for the formation of the lysolecithinic acid has not yet been obtained. Passage of lysolecithin through silicic acid causes ester migration from the beta to the alpha position of glycerol. This is reflected by an increase in the keto-lysolecithin upon bromine oxidation. A novel reaction occurs when lysolecithin is treated with bromine in chloroform or methanol. Brominolysis rather than oxidation takes place with the formation of lysophosphatic acids and choline. A discussion of these findings is presented.