Intramolecular regioselective addition of radicals and carbanions to ynol ethers. A strategy for the synthesis of exocyclic enol ethers

The scope and limitations of radical and anionic cyclization reactions involving halo ynol ethers have been investigated. 5-exo and 6-exo radical cyclizations of 6-iodo and 7-iodo ynol ethers proceeded well when the oxygen of the ynol ether was bearing an ethyl group. Exocyclic iodoenol ethers resulting from these cyclizations were highly unstable and decomposed rapidly. Li-I exchange of iodo ynol ethers proceeded smoothly at −78 °C. 6-Alkoxy-5-hexynyllithiums underwent regiospecific 5-exo-dig anionic cyclization to produce five-membered rings bearing an exocyclic enol ether moiety. The cyclized vinyllithium intermediate was successfully trapped with electrophiles to afford functionalized cycloalkoxyalkylidene derivatives in modest to good yields. 7-Alkoxy-6-heptynyllithiums did not cyclize via a 6-exo anionic process.     

Synthesis of enol ethers from lactones using modified Julia olefination reagents: application to the preparation of tri- and tetrasubstituted exoglycals

A new route to substituted exoglycals from the corresponding lactones is described. The enol ethers synthesis via a modified Julia olefination of sugar-derived lactones is extended to substituted benzothiazolyl sulfones to furnish tri- and tetrasubstituted exoglycals.     

Straightforward α-carbamoylation of NADH-like dihydropyridines and enol ethers

The protonation of NADH-like dihydropyridines and cyclic enol ethers generates reactive cationic intermediates, which interact with isocyanides to afford α-carbamoylated heterocycles after an aqueous quenching, in Ugi and Passerini-type reactions, thus broadening the scope of these multicomponent processes.     

Synthesis of cyclobutanones and four-membered enol ethers by using a rearrangement reaction of enol triflates

A new synthetic method of cyclobutanone derivatives and four-membered enol ethers via an intramolecular cyclization of a ketone enolate was developed. The cyclization precursors, enol triflates having a silyloxy group at the β′-position, were synthesized from the corresponding β-hydroxy ketones, which were prepared via an aldol reaction of a cycloalkanone and an aldehyde. Under the influence of TBAF, the enol triflates afforded a cyclobutanone or a four-membered enol ether through rearrangement of the trifluoromethanesulfonyl group followed by an intramolecular C- or O-alkylation reaction.     

Preparation of enol ethers by carbonyl olefination utilizing an alkoxymethyl chloride-titanocene(II) system

Aldehydes, ketones, esters and lactones are transformed into enol ethers or 1,2-dialkoxy-1-alkenes by treatment with organotitanium species prepared from alkoxymethyl chlorides and a titanocene(II) complex.     

Regioselective synthesis of bis(silyl enol ethers) and bis(conjugated enones) through electron transfer from Mg metal

Treatment of α,β-unsaturated ketones with Mg metal in the presence of trimethylsilyl choride (TMSCl) brought about facile and regioselective reductive dimerization to give the corresponding bis(silyl enol ethers), 1,6-bis(trimethylsilyloxy)-1,5-dienes. Similar Mg-promoted reductive dimerization of 1,3-cyclic diketones in the presence of TMSCl followed by acid-catalyzed hydrolysis led to selective formation of the corresponding 1,6-diketo-2,4-dienes in moderate to good yields.     

Synthesis of enamines, enol ethers and related compounds by cross-coupling reactions

For several decades, enamines and related compounds have been used as intermediates in organic synthesis and many methods are known for their preparation. Most of the synthetic protocols, however, require harsh reaction conditions. Recently, a new approach has emerged, inspired by the analogous arylation of amines catalysed by palladium or copper complexes (Buchwald-Hartwig reaction). Simultaneous and independent work from several research groups has led to the development of very powerful protocols for the preparation of enamines and their derivatives that require only readily available starting materials and proceed under very mild reaction conditions. Noteworthy is the fact that in less than five years an almost unknown reaction has reached such a high level of scope and generality that it is now very frequently applied in total syntheses of natural products.     

Arylation of [6,6]-spiroacetal enol ethers: reactivity and rearrangement

Attempts to selectively arylate [6,6]-spiroacetal enol ethers at the 2-position delivered unexpected results. Palladium-mediated arylation conditions afforded the double-Heck product, whereas reaction with benzenesulfinic acid resulted in a facile rearrangement into the corresponding 5-phenylsulfonyl-3,4,5,6-tetrahydrochromans, providing access to 5-aryl-3,4,5,6-tetrahydrochroman and hexahydrochroman derivatives.     

Stereoselective hetero-Diels–Alder reaction of 3-(polyfluoroacyl)chromones with enol ethers. Novel synthesis of 2-R-containing nicotinic acid derivatives

3-(Polyfluoroacyl)chromones undergo heterodiene cycloaddition to 3,4-dihydro-2H-pyran, 2,3-dihydrofuran and ethyl vinyl ether under mild conditions, producing novel fused pyrans with high stereoselectivity and in good yields. Some of these pyrans were transformed into 2-R^F-containing pyridines on treatment with ammonium acetate in ethanol.     

Evaluation of C-trialkylsilyl enol and thioenol ethers as intermediates in the synthesis of acylsilanes

C-silyl enol ethers or thioenol ethers have been prepared by a Peterson reaction, as intermediates for acylsilane synthesis. Bis(trialkylsilyl)(methoxy)- or -(methylsulfanyl)methanes bearing identical or different trialkylsilyl groups were used as starting materials in order to assess the selectivity of the Peterson elimination step. A good selectivity was observed only with ethers bearing the TMS and TBDMS groups. However, there is no practical interest to use such reagents owing to the difficulty to obtain them in correct yields. Bis(trimethylsilyl)(methylsulfanyl)methane proved to be a good reagent for the preparation of C-silyl thioenol ethers, which are hydrolyzed under classical acid conditions to give acylsilanes in fair overall yields. This convenient procedure was extended to the synthesis of bis(acylsilanes).     

Low temperature syntheses of thioketals from enol ethers and carbonyl compounds

A dithioacetalisation procedure at low temperature using TMSOTf as the promoter is described. This method proved highly efficient for unprecedented transprotection of ketone enol ethers and was successfully applied to polyfunctional sensitive substrates.     

Petasis vs. Strecker Amino Acid Synthesis: Convergence,Divergence and Opportunities in Organic Synthesis

α-Amino acids find widespread applications in various areas of life and physical sciences. Their syntheses are carried out by a multitude of protocols, of which Petasis and Strecker reactions have emerged as the most straightforward and most widely used. Both reactions are three-component reactions using the same starting materials, except the nucleophilic species. The differences and similarities between these two important reactions are highlighted in this review.     

Synthesis of 3,5-dioxoalkanoates, 3,5-dioxopimelates and 2,4-dioxoadipates by acylation of 1,3-bis-silyl enol ethers

3,5-Dioxoalkanoates, 3,5-dioxopimelates and 2,4-dioxoadipates were prepared by acylation of 1,3-bis-silyl enol ethers with carboxylic chlorides, methyl 3-chloro-3-oxopropanoate and ethyl 2-chloro-2-oxoacetate, respectively.     

Gold- and silver-catalyzed highly regioselective addition of active methylenes to dienes, triene, and cyclic enol ethers

The combination of gold and silver salts catalyzed the addition of active methylenes to dienes, triene, and cyclic enol ethers with high regioselectivity. The catalysis provides a synthetically useful method for functionalized carbocycles and heterocycles through a highly atom-economical carbon-carbon bond formation. [reaction: see text]     

1-Phenylthio-3-vinyl-3-cyclohexenol, a new reagent for bis-annelation of silyl enol ethers

1-Phenylthio-3-vinyl-cyclohex-1-en-3-ol (2) has been synthesized and investigated as a new bis-annelation reagent for silyl enol ethers. Reagent 2 can be synthesized by a Grignard reaction of vinyl magnesium bromide with 3-phenylthiocyclohexenone. The reaction with silyl enol ethers takes place under Lewis acid catalysis and generally proceeds in good yields. The resulting phenylthiodienes can be hydrolyzed to enones, which have been cyclized in a homologous aldol reaction to polycyclic compounds.     

An efficient HCl promoted Petasis reaction of 2-pyridinecarbaldehydes,amines and 1,2-oxborol-2(5H)-ols

A Petasis reaction of 2-pyridinecarbaldehydes with various amines and 4-substituted 1,2-oxaborol-2(5H)-ols was developed. In the presence of HCl, the reaction proceeded smoothly under very mild conditions and the corresponding desired products were obtained in medium to excellent yields. This method allows the access a wide range of highly functionalized allylic alcohols, which might be useful compounds in medicinal and material chemistry.     

Synthesis of novel crown ethers. Part 1. Coumestan and coumestan analog derivatives of crown ethers

The presented ethylenedioxy compounds5a,5d,6a and6c are examples of novel cyclic ethers, while macrocyclic polyethers represent new crown ether analogues. New coumestan-crowns5a-f, derivatives of 6,7-dihydroxy-3,4-dihydro-2H-dibenzofuran-1-one and 6,7-dihydroxy-3,3-dimethyl-3,4-dihydro-2H-dibenzofuran-1-one6a-e were synthesized from the correspondingo-dihydroxy compounds3a-b,4a-b and ditosylates or dichlorides of di- or triethylene glycol in the presence of K₂CO₃, in DMF/H₂O (15/1) solutions at 65–75 °C for 35 hours. The structure of the macrocyclic ethers obtained were confirmed by¹H-NMR,¹³C-NMR, IR spectra and elemental analyses.Presented at the Sixth International Seminar on Inclusion Compounds, Istanbul, Turkey, 27–31 August, 1995.     

Sodium dithionite initiated reactions of 1-bromo-1-chloro-2,2,2-trifluoroethane with enol ethers of cyclic ketones

Sodium dithionite initiated reactions of 1-bromo-1-chloro-2,2,2-trifluoroethane (1) with methyl and trimethylsilyl ethers of cyclopentanone and cyclohexanone enols (2a-d) in a MeCN/H₂O system were investigated. 2-(2,2,2-Trifluoroethylidene)cyclopentanone (4a) and 2-(2,2,2-trifluoroethylidene)-cyclohexanone (4b), respectively, were obtained as the main products and isolated in reasonable yields. The reaction with a 1:1 mixture of 5- and 3-methyl substituted 1-methoxycyclohexenes, 2e and 2f, revealed strong influence of steric hindrance on the reaction rate; a mixture of 2-(2,2,2-trifluoroethylidene)-5-methylcyclohexanone (6) and 2-(2,2,2-trifluoroethylidene)-3-methylcyclohexanone (7) in a 9:1 ratio was formed. Ketones 4a and 4b were reduced to the corresponding alcohols 8 and 9 and the reaction of 4b with hydrazine gave an indazole derivative 10.