Enolate Chemistry Research Articles

Multistep Synthesis of a Terphenyl Derivative Showcasing the Diels–Alder Reaction

An adaptable multistep synthesis project designed for the culmination of a second-year organic chemistry laboratory course is described. The target compound is a terphenyl derivative that is an intermediate in the synthesis of compounds used in organic light-emitting devices. Students react a conjugated diene with dimethylacetylene dicarboxylate in a Diels–Alder reaction, then use enolate chemistry to isomerize and aromatize the adduct. Analysis of the synthesized intermediates and final compound is accomplished by thin-layer chromatography, NMR, and melting point. The synthesis can be expanded to four or five steps by linking to a previously published preparation of the diene. In addition to gaining experience with classic reactions in undergraduate organic chemistry courses, students are exposed to the utility of NMR spectroscopy by tracking subtle changes in the NMR spectra of structurally similar species.

Comparing Carbonyl Chemistry in Comprehensive Introductory Organic Chemistry Textbooks

Learning the chemistry of compounds containing carbonyl groups is difficult for undergraduate students partly because of a convolution of multiple possible reaction sites, competitive reactions taking place at those sites, different criteria needed to discern between the mechanisms of these reactions, and no straightforward selection method applicable to all. Factual inaccuracies in some recently used comprehensive introductory organic chemistry textbooks can distract and confuse students. Student interest, combined with some inconsistencies, prompted a systematic comparison of these textbooks, enabling some suggestions for improvement. Students also selected a preferred order of presentation in which carbonyl chemistry should appear for optimal learning: carboxylic acids, aldehydes, ketones, carboxylic acid derivatives, α,β-unsaturated carbonyls, and carbonyl compounds that undergo enol chemistry. This ordering is generally based on a combination of (1) grouping according to the purpose of the functional...

Atmospheric chemistry of enols: a theoretical study of the vinyl alcohol + OH + O(2) reaction mechanism.

Enols are emerging as trace atmospheric components that may play a significant role in the formation of organic acids in the atmosphere. We have investigated the hydroxyl radical ((•)OH) initiated oxidation chemistry of the simplest enol, vinyl alcohol (ethenol, CH2═CHOH), using quantum chemical calculations and energy-grained master equation simulations. A lifetime of around 4 h was determined for vinyl alcohol in the presence of tropospheric levels of (•)OH. The reaction proceeds by (•)OH addition at both the α (66%) and β (33%) carbons of the π-system, yielding the C-centered radicals (•)CH2CH(OH)2, and HOCH2C(•)HOH, respectively. Subsequent trapping by O2 leads to the respective peroxyl radicals. About 90% of the chemically activated population of the major peroxyl radical adduct (•)O2CH2CH(OH)2 is predicted to undergo fragmentation to produce formic acid and formaldehyde, with regeneration of (•)OH. The minor peroxyl radical HOCH2C(OO(•))HOH is even less stable and undergoes almost exclusive HO2(•) elimination to form glycolaldehyde (HOCH2CHO). Formation of the latter has not been proposed before in the oxidation of vinyl alcohol. A kinetic mechanism for use in atmospheric modeling is provided, featuring phenomenological rate coefficients for formation of the three main product channels ((•)O2CH2CH(OH)2 [8%]; HC(O)OH + HCHO + (•)OH [56%]; HOCH2CHO + HO2(•) [37%]). Our study supports previous findings that vinyl alcohol should be rapidly removed from the atmosphere by reaction with (•)OH and O2 with glycolaldehyde being identified as a previously unconsidered product. Most importantly, it is shown that direct chemically activated reactions can lead to (•)OH and HO2(•) (HOx) recycling.

Enolate chemistry with anion-π interactions.

Anion-π interactions occur on the surface of π-acidic aromatic planes with positive quadrupole moments. Their ability to contribute to the binding and transport of anions has been demonstrated recently. However, their ability to stabilize anionic reactive intermediates and transition states remains essentially unexplored. This situation is contrary to the recognized importance of the complementary cation-π interactions to catalyse most important reactions in biology and chemistry. In this report, we provide direct experimental evidence that already single unoptimized anion-π interactions can stabilize enolates by almost two pKa units. The addition of these anion-π-stabilized reactive enolate intermediates to enones and nitroolefins occurs with transition-state stabilizations of up to 11 kJ mol(-1), and anionic cascade reactions accelerate on π-acidic surfaces. These findings are significant because enolate chemistry is central in chemistry and biology, and they will stimulate the use of anion-π interactions in catalysis in the broadest sense.

Multicomponent Heterocyclic Chemistry for Undergraduate Organic Laboratory: Biginelli Reaction with Multiple Unknowns

Multicomponent reactions and heterocyclic chemistry are important concepts of organic synthesis, especially in the pharmaceutical industry. A one-pot, multicomponent Biginelli condensation reaction to synthesize dihydropyrimidine derivatives from multiple unknowns is investigated as a discovery-based experiment in a second semester, second-year undergraduate organic chemistry laboratory course. Three 1,3-dicarbonyl compounds, two aryl aldehydes, and urea are utilized to provide six different unknown dihydropyrimidine derivatives with average yields ranging from 63–79%. Students identify their products using 1H NMR, 13C NMR, DEPT, and IR spectroscopic data. The experiment provides an opportunity to discuss multicomponent reactions, carbonyl condensations with amines, enol chemistry, and interpretation of spectra, while being completed in a 3-h laboratory period.

Diastereoselective synthesis of cyclic β2,3-amino acids utilizing 4-substituted-1,3-oxazinan-6-ones

The 4-substituted-1,3-oxazinan-6-one scaffold is a versatile synthon enabling access to a diverse array of β-amino acid derivatives. In this study, the synthetic utility of the 1,3-oxazinan-6-one is expanded to include the diastereoselective synthesis of cyclic β2,3-amino acids. Enolate chemistry is used to first alkylate the 4-vinyl, 4-allyl, and 4-butenyl oxazinan-6-ones with various alkenyl electrophiles, in high dr. The resulting 4,5-bis-alkene adducts are then transformed into 4,5-cyclic-1,3-oxazinan-6-ones utilizing the ring closing metathesis reaction. The metathesis products are subsequently converted into a variety of five-, six-, and seven-membered cyclic β2,3-amino acids. The research further highlights the 1,3-oxazinan-6-one as a versatile synthon for producing β-amino acid derivatives.

The cascade radical cyclisation approach to prenylated alkaloids: synthesis of stephacidin A and notoamide B

A strategy for the synthesis of members of the prenylated indole alkaloid family is described, which involves a radical cascade process of an appropriately substituted diketopiperazine (DKP) core structure. Several approaches to the generation of the initial radical were explored, with the most successful involving treatment of a sulfenyl substituted DKP under classical reductive conditions by heating with Bu3SnH and a radical initiator. The required, fully substituted, radical precursor DKP structures were prepared using regio- and stereocontrolled enolate chemistry of simpler proline-tryptophan derived DKPs. The new approach allowed rapid access to a key polycyclic indoline structure, which was converted into either of the natural products stephacidin A or notoamide B.

A shock tube and chemical kinetic modeling study of the pyrolysis and oxidation of butanols

The pyrolysis and oxidation of all four butanols (n-, sec-, iso- and tert-) have been studied at pressures from 1 to 4atm and temperatures of 1000–1800K behind reflected shock waves. Gas chromatographic sampling at different reaction times varying from 1.5 to 3.1ms was used to measure reactant, intermediate and product species profiles in a single-pulse shock tube. In addition, ignition delays were determined at an average reflected shock pressure of 3.5atm at temperatures from 1250 to 1800K. A detailed chemical kinetic model consisting of 1892 reactions involving 284 species was constructed and tested against species profiles and ignition delays. The little-known chemistry of enols is included in this work to explain the temperature dependence of acetaldehyde produced in the thermal decomposition of isobutanol.

ChemInform Abstract: Carbon—Carbon Bond‐Forming Reactions of α‐Carbonyl Carbocations: Exploration of a Reversed‐Polarity Equivalent of Enolate Chemistry.

AbstractSilver‐promoted ionization of α‐halocarbonyl compounds generates the corresponding α‐carbonyl carbocations which smoothly react with simple (het)arenes as nucleophiles to give diarylcarbonyl compounds, e.g. (III), (V)/(VI) and (XII).

Carbon–carbon bond-forming reactions of α-carbonyl carbocations: exploration of a reversed-polarity equivalent of enolate chemistry

Carbon–carbon bond-forming reactions of putative α-carbonyl carbocation intermediates generated by Lewis acid- or silver-promoted ionizations of toluenesulfonate or halide leaving groups are described. This under-exploited mode of reactivity represents an ‘umpolung’ of conventional enolate chemistry, and enables C–C bond construction in both intra- and intermolecular contexts. Attempts to develop diastereoselective variants of this process using chiral ester and oxazolidinone-based auxiliaries are discussed.

Stereoselective C–C bond formation catalysed by engineered carboxymethylproline synthases

The reaction of enol(ate)s with electrophiles is used extensively in organic synthesis for stereoselective C-C bond formation. Protein-based catalysts have had comparatively limited application for the stereoselective formation of C-C bonds of choice via enolate chemistry. We describe protein engineering studies on 5-carboxymethylproline synthases, members of the crotonase superfamily, aimed at enabling stereoselective C-C bond formation leading to N-heterocycles via control of trisubstituted enolate intermediates. Active site substitutions, including at the oxyanion binding site, enable the production of substituted N-heterocycles in high diastereomeric excesses via stereocontrolled enolate formation and reaction. The results reveal the potential of the ubiquitous crotonase superfamily as adaptable catalysts for the control of enolate chemistry.

エナミン誘導体の極性転換による炭素‐炭素結合構築法

Umpolung chemistry has been the focus of research on organic synthesis due to its usefulness and unusual reactivity. Above all, umpolung of enamine property enables the formation of highly substituted carbon-carbon bonds and installation of aryl groups on sp3 carbon atoms, which are difficult to realize by normal enolate chemistry. This short review describes recent reports of the carbon-carbon bond formation by umpolung reactions of enamine derivatives.

ChemInform Abstract: The Chemistry of Enols. The Chemistry of Ionized Enols in the Gas Phase

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: The Chemistry of Enols. Kinetics and Mechanism of Enolization and Ketonization

ChemInform Abstract: The Chemistry of Enols. Kinetics and Mechanism of Enolization and Ketonization

ChemInform Abstract: The Chemistry of Enols. Photochemical Reactions Involving Enols

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: The Chemistry of Enols. NMR, IR, Conformation and Hydrogen Bonding

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: The Chemistry of Enols. Enols of Carboxylic Acids and Esters

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: The Chemistry of Enols. Isolable and Relatively Stable Simple Enols

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Enols and Other Reactive Species

Rapid advances in the chemistry of enols and other reactive species have been made possible recently by the development of methods for generating these short-lived substances in solution under conditions where they can be observed directly and their reactions can be monitored accurately. New laboratory techniques are described and a sample of the new chemistry they have made available is provided; special attention is given to ynols and ynamines and the remarkable effects that the carbon-carbon triple bonds of these substances have on their acid-base properties.

ChemInform Abstract: Perfluorinated Enolate Chemistry. Selective Generation and Unique Reactivities of Ketone F-Enolates

ChemInform Abstract: Perfluorinated Enolate Chemistry. Selective Generation and Unique Reactivities of Ketone F-Enolates