Generation Of Enolates Research Articles

A DFT study on the formation mechanism of side product 1,2-propanediol in the hydrogenation of dimethyl oxalate over copper catalyst

The costly separation of 1,2-propanediol (1,2-PDO), an unavoidable byproduct in the hydrogenation of dimethyl oxalate (DMO), significantly hampers the economic viability of coal-to-ethylene glycol (EG) technology. To address this challenge, the formation mechanism of the side product 1,2-PDO on the Cu(111) and Cu2O(111) surfaces during DMO hydrogenation was investigated, which focused on the active sites of copper catalyst and the dominant pathway through density functional theory calculation. The thermodynamics of each elementary step and the adsorption behavior of various species involved in the reaction network along with the local density of states and charge density difference were systematically analyzed. The results indicate that 1,2-PDO is generated more favorably on the Cu2O(111) surface than that on the Cu(111) surface, owing to the Lewis acid-base pairs, i.e. Cu+ us and O– suf sites, present on the Cu2O(111) surface, which strengthens the binding of reactants, products, and reaction intermediates to the substrate. EG reacts primarily with methanol (MeOH) to form 1,2-PDO through Guerbet alcohol condensation reaction through three consecutive steps: alcohol dehydrogenation, aldol condensation, and unsaturated aldehyde hydrogenation. The O– suf sites promote the dehydrogenation of alcohols into aldehydes, the generation of enolates during aldol condensation and the hydrogenation of unsaturated aldehydes, while the Cu+ us sites are responsible for the C–C coupling reaction. These findings may shed light on the mechanism of 1,2-PDO formation over Cu catalyst and provide fundamental knowledge for the development of more efficient catalysts and process optimization.

N‐Heterocyclic Carbene Organocatalyzed [3+3] Annulation for the Enantioselective Synthesis of Benzopyranothiazinones

AbstractThe design, inspired by the core‐structure of oxicam has allowed the enantioselective synthesis of benzopyranothiazinone motifs employing N‐heterocyclic carbene (NHC) catalysis. The NHC‐mediated transformation involves the reaction of α,β‐unsaturated aldehydes with suitable substituted benzothiazinone derivatives. This process encompasses the initial formation of α,β‐unsaturated acylazoliums from ynals and concurrent generation of enolates from benzothiazinone. The culmination of these reactions results in an efficient annulation, yielding the desired products with reasonable yields and high stereoselectivities. This study underscores the potential of NHC catalysis in the streamlined synthesis of complex heterocyclic structures.

Lewis Base-assisted Arylation of Unsaturated Carbonyls.

The combination of Lewis bases with α,β-unsaturated carbonyls allows the in-situ generation of enolates without the need for strong Brønsted bases. Recently developed synthetic methods employ this approach for arylation followed by elimination of the Lewis base, regenerating the alkene. This strategy has been deployed for formal α- or β-C-H arylation in different contexts, namely (a) transition metal catalysis, (b) rearrangement reactions utilizing hypervalent main group elements and (c) organocatalysis. This concept article provides an overview of the developed strategies, highlighting and contextualizing their features.

Photochemical Wolff Rearrangement Initiated Generation and Subsequent α-Chlorination of C1 Ammonium Enolates.

The enantioselective synthesis of α-chlorinated carboxylic acid esters with er up to 99:1 and yields up to 82% was achieved via a one-pot multistep protocol starting from α-diazoketones. This process proceeds via a photochemical Wolff rearrangement, trapping of the generated ketene with a chiral Lewis base catalyst, subsequent enantioselective α-chlorination, and a final nucleophilic displacement of the bound catalyst. The obtained products were successfully utilized for stereospecific nucleophilic displacement reactions with N- and S-nucleophiles.

Diethylzinc‐Mediated Cross‐Coupling Reactions between Dibromoketones and Monobromo Carbonyl Compounds

AbstractA novel route to synthesize 1,4‐dicarbonyl compounds is described. α,α‐Dibromoketones generate zinc enolates through a diethylzinc‐mediated halogen‐metal exchange and react with α‐bromocarbonyl compounds to furnish 1,4‐dicarbonyl compounds via a second generation of zinc enolates. This cross‐coupling reaction is enabled by the chemoselective formation of zinc enolates from α,α‐dibromoketones in the presence of α‐bromocarbonyl compounds. Chiral 1,4‐dicarbonyl compounds can be obtained via the enantioselective bromination of aldehydes using a chiral secondary amine catalyst and a subsequent cross‐coupling reaction between the resulting chiral α‐bromoaldehydes and α,α‐dibromoacetophenones.

Diethylzinc-Mediated Cross-Coupling Reactions between Dibromoketones and Monobromo Carbonyl Compounds.

A novel route to synthesize 1,4-dicarbonyl compounds is described. α,α-Dibromoketones generate zinc enolates through a diethylzinc-mediated halogen-metal exchange and react with α-bromocarbonyl compounds to furnish 1,4-dicarbonyl compounds via a second generation of zinc enolates. This cross-coupling reaction is enabled by the chemoselective formation of zinc enolates from α,α-dibromoketones in the presence of α-bromocarbonyl compounds. Chiral 1,4-dicarbonyl compounds can be obtained via the enantioselective bromination of aldehydes using a chiral secondary amine catalyst and a subsequent cross-coupling reaction between the resulting chiral α-bromoaldehydes and α,α-dibromoacetophenones. This approach provides various chiral 1,4-dicarbonyl compounds with high enantioselectivity from readily available aldehydes and α,α,α-tribromoketones under mild conditions.

Sigmatropic [1,5] Carbon Shift of Transient C3 Ammonium Enolates.

The stereospecific sigmatropic [1,5] carbon shift of C3 ammonium enolates is discovered. According to mechanistic, kinetic and computational experiments, this new rearrangement proceeds via the catalytic generation of a transient C3 ammonium enolate by intramolecular aza‐Michael addition. This intermediate rapidly undergoes [1,5] sigmatropic carbon migration to furnish the respective tetrahydroquinoline‐4‐ones with excellent diastereoselectivities of d.r. >99 : 1 and in 61–98 % yield.

Mechanistic Insight into the 1,3,2-Diazaphospholene-Catalyzed Reductant (HBpin/NH3BH3)-Controlled Reaction of Allyl 2-Phenylacrylate: Claisen Rearrangement or Hydrogenation?

Mechanistic study on the 1,3,2-diazaphospholene (1)-catalyzed reduction reaction of allyl 2-phenylacrylate 4 with HBpin or ammonia borane (AB) was systematically performed by the density functional theory (DFT) method. When HBpin is employed as the reductant, the reductive Ireland-Claisen (IC) rearrangement reaction occurs. First, the active species P-hydrido-1,3,2-diazaphospholene 3 is generated through the metathesis reaction of 1 with HBpin. Next, the terminal C═C double bond of 4 is inserted into the P-H bond of 3 to produce 6a through the 1,2-addition (Markovnikov) step, which is followed by the pinB-H bond activation to afford key boron enolate 8. Then, 8 undergoes the [3,3] rearrangement that is followed by the alcoholysis reaction with methanol leading to the final product γ,δ-unsaturated carboxylic acid. The [3,3] rearrangement step is the rate-determining step with the Gibbs energy barrier (ΔG≠) and Gibbs reaction energy (ΔG) of 23.9 and -27.5 kcal/mol, respectively. When AB is employed as the reductant, the transfer hydrogenation reaction occurs through two comparable pathways, 1,2- and 1,4-transfer hydrogenation pathways. The former pathway directly leads to the hydrogenation product with the ΔG≠ and ΔG values of 22.4 and -27.7 kcal/mol, respectively. The latter pathway produces an enolate intermediate (rate-determining step, ΔG≠/ΔG = 24.1/-0.3 kcal/mol) first, which then prefers to undergo the enol-keto tautomerism instead of the [3,3] rearrangement to afford the hydrogenation product. Obviously, the generation of the boron enolate plays a crucial role in the reductive IC rearrangement reaction because it prevents the enol-keto tautomerism.

Cooligomerization of γ-butyrolactone with (meth)acrylates catalyzed by N-heterocyclic carbene: Low possibility of hybrid copolymerization

Copolymerization between lactones and vinyl monomers has significant implications for the synthesis of new polymeric materials; however, a highly reactive cyclic monomer, e.g., ε-caprolactone (CL), leads to a copolymeric product but with a complex structure remaining to be elucidated. Herein, we present cooligomerizations of γ-butyrolactone (γBL), a low-polymerizable cyclic monomer, with (meth)acrylates catalyzed by an N-heterocyclic carbene (NHC) under conditions in which no reaction occurs in the absence of either comonomer. Several experimental studies indicate that the product is not a hybrid cooligomer with an ester linkage in the main chain but a graft cooligomer. The reaction mechanism involves the generation of the γBL enolate by the NHC to initiate oligomerizations of γBL and (meth)acrylates followed by the transesterification of oligo (γBL) with an ester unit of (meth)acrylates. These results prompted us to investigate the previously reported structure of copolymer of CL and methyl methacrylate obtained by a phosphazene base catalyst. The hydrolysis experiment revealed that the copolymeric product turned out not to be a hybrid random copolymer.

Introducing deep eutectic solvents in enolate chemistry: synthesis of 1-arylpropan-2-ones under aerobic conditions

An environmentally friendly procedure for the generation of enolates from 1-arylpropan-2-ones, followed by functionalization with electrophiles and (hetero)aryl halides in deep eutectic solvents under aerobic conditions, is disclosed.

Nickel-catalyzed reductive coupling of homoenolates and their higher homologues with unactivated alkyl bromides

The catalytic generation of homoenolates and their higher homologues has been a long-standing challenge. Like the generation of transition metal enolates, which have been used to great affect in synthesis and medicinal chemistries, homoenolates and their higher homologues have much potential, albeit largely unrealized. Herein, a nickel-catalyzed generation of homoenolates, and their higher homologues, via decarbonylation of readily available cyclic anhydrides has been developed. The utility of nickel-bound homoenolates and their higher homologues is demonstrated by cross-coupling with unactivated alkyl bromides, generating a diverse array of aliphatic acids. A broad range of functional groups is tolerated. Preliminary mechanistic studies demonstrate that: (1) oxidative addition of anhydrides by the catalyst is faster than oxidative addition of alkyl bromides; (2) nickel bound metallocycles are involved in this transformation and (3) the catalyst undergoes a single electron transfer (SET) process with the alkyl bromide.

Acylation of oxindoles using methyl/phenyl esters via the mixed Claisen condensation - an access to 3-alkylideneoxindoles.

Predominantly, aggressive acid chlorides and stoichiometric coupling reagents are employed in the acylating process for synthesizing carbonyl tethered heterocycles. Herein, we report simple acyl sources, viz. methyl and phenyl esters, which acylate oxindoles via the mixed Claisen condensation. This straightforward protocol is mediated by LiHMDS and KOtBu and successfully applied to a wide range of substrates. It is a noteworthy transformation that skips the stepwise generation of enolates and acylation, and the reaction is performed at a moderate temperature with no side reactions. This protocol produces the first examples of ortho-substituents in an aryl ring flanked with electron-donating and electron-withdrawing substrates. Interestingly, robust organometallic ferrocenyl methyl ester cleaved under these conditions with ease. Furthermore, biologically important Tenidap's analog was synthesized by this protocol.

Palladium-Catalyzed Generation of C1 Ammonium Enolates

Key words palladium catalysis - ammonium enolates - dihydropyridones - β-lactams

N-Heterocyclic carbene-catalyzed [4 + 2] cyclization of α-chloroaldehydes and aurones: Highly enantioselective synthesis of benzofuran-fused dihydropyran-2-ones

The chiral N-heterocyclic carbene-catalyzed [4+2] annulation of α-chloroaldehydes and aurones was developed, giving the corresponding benzofuran–fused dihydropyranones in good to high yields with good diastereoselectivities and excellent enantioselectivities. The catalytic cycle features with the generation of enolate from chloroaldehdye and its following [4+2] cycloaddtion with aurones.

Enantioselective Direct Mannich‐Type Reactions Catalyzed by Frustrated Lewis Acid/Brønsted Base Complexes

AbstractAn enantioselective direct Mannich‐type reaction catalyzed by a sterically frustrated Lewis acid/Brønsted base complex is disclosed. Cooperative functioning of the chiral Lewis acid and achiral Brønsted base components gives rise to in situ enolate generation from monocarbonyl compounds. Subsequent reaction with hydrogen‐bond‐activated aldimines delivers β‐aminocarbonyl compounds with high enantiomeric purity.

Enantioselective Direct Mannich-Type Reactions Catalyzed by Frustrated Lewis Acid/Brønsted Base Complexes.

An enantioselective direct Mannich-type reaction catalyzed by a sterically frustrated Lewis acid/Brønsted base complex is disclosed. Cooperative functioning of the chiral Lewis acid and achiral Brønsted base components gives rise to in situ enolate generation from monocarbonyl compounds. Subsequent reaction with hydrogen-bond-activated aldimines delivers β-aminocarbonyl compounds with high enantiomeric purity.

Frustrated Lewis Acid/Brønsted Base Catalysts for Direct Enantioselective α-Amination of Carbonyl Compounds.

A method for enantioselective direct α-amination reaction catalyzed by a sterically "frustrated" Lewis acid/Brønsted base complex is disclosed. Cooperative functioning of the Lewis acid and Brønsted base components gives rise to in situ enolate generation from monocarbonyl compounds. Subsequent reaction with hydrogen-bond activated dialkyl azodicarboxylates delivers α-aminocarbonyl compounds in high enantiomeric purity.

Stereoselective Alkylation of Imines and its Application towards the Synthesis of β‐Lactams

Abstract(S)‐4‐Isopropyl‐1‐[(R)‐1‐phenylethyl]imidazolidin‐2‐one was evaluated as a chiral auxiliary for asymmetric acetate and propionate Mannich‐type reactions, by generation of the titanium enolates, affording excellent yields and stereoselectivities. The application of the auxiliary was exemplified in the stereoselective synthesis of the β‐lactam antihyperlipidemic drug ezetimibe.

First Isolation and Characterization of the Highly Coordinated Group 14 Enolates: Effects of the Coordination Controls on the Geometry and Tautomerization of Germyl Enolates

The Group 14 enolates play an important part in many organic reactions. Herein, the reduction of an α-bromo ketone with germanium(II) salts cleanly afforded the corresponding germyl enolate as an isolatable species. This experimental reductive generation of a germyl enolate enabled us to characterize both C- and O-bound tautomers derived from an identical precursor and to unveil the tautomeric mechanisms, including the kinetic parameters and the relative stability of these tautomers, along with confirmation from DFT calculations. Moreover, the highly coordinated germyl enolates were isolated by a stabilization process induced by adding ligands. All products were characterized by NMR spectroscopy and X-ray crystallography.

Synthesis of novel chiral heterometallic terpene oximates: unusual generation of an aluminium enolate by a cooperative effect.

Al-K heterometallic terpene oximate derivatives with uncommon structural features are reported. These species react with an aryl ketone leading to heterometallic enolates via an unusual route. Isolation of a remarkable heterometallic Al-K enolate confirms the cooperative mechanism proposed by DFT calculations, where the oximate ligand has a prominent role. From these enolates the formation of new C-C bonds is straightforward.