Catalytic asymmetric chloroamination reaction of α,β-unsaturated γ-keto esters and chalcones

Highly efficient catalytic chloroamination reaction of α,β-unsaturated γ-keto esters and chalcones has been developed via a chloronium-based mechanism to deliver anti-regioselective vicinal chloroamines instead of the aziridinium intermediates delivered aminochlorides. The combination of TsNCl(2) and TsNH(2) as reagents made the transformation highly efficient, delivering the γ-carbonyl-β-chloro-α-amino acid derivatives and α-chloro-β-amino-ketone derivatives in nearly quantitative yields with up to 99% ee and 99:1 dr under 0.05-0.5 mol % catalyst loading. TsNHCl was demonstrated to act as the key reactive species to form a bridged chloronium ion intermediate in the presence of a chiral scandium complex. The method might provide useful information for further realization of other haloamination reactions.     

Stereoselective cycloaddition of N-acyliminium cations withα,β-unsaturated ketones and esters

The cycloaddition of N-acyliminium cations with some deactivated alkenes such asα,β-unsaturate ketones and esters has been investigated.In most cases,the N-acyliminium cations produced from 3-hydroxy-2-arylisoindol-1-ones in the presence of BF_3·OEt_2 could be reacted withα,β-unsaturated ketones and esters to afford stereoselectively the cycloaddition products 6-acylisoindolo[2,1-a] quinolin-11-ones in moderate to high yields.     

Decomposition of benzenediazonium fluoborate in esters of α,β-unsaturated acids

Summary It was shown that In contrast to the Meerwein-Koelsch reaction, the decomposition of benzenediazonlum fluoborate In esters of ,-unsaturated acids proceeds by a heterolytlc mechanism with the phenyl attacking the -carbon and the carbalkoxyl group of these esters. The reaction with ethyl crotonate gave -methylatropic acid (after hydrolysis) and a small amount of a dibasic acid, C₁₄H₁₆O₄ (or C₁₄H₁₄O₄). With methyl acrylate it gave atropic acid, phenyl acrylate, and a smaller amount of -methyl--phenylglutaric acid. With methyl methacrylate It formed benzylacrylic acid and the product of further conversions of phenyl methacrylate, namely the keto phenol 2-methyl-5-hydroxyindan-1-one.     

Double asymmetric induction in the osmylation of -γ-alkoxy-α,β-unsaturated esters

OsO₄ promoted cis-dihydroxylation of enantiomerically pure (E)-α,β- unsaturated esters derived from alkoxyaldehydes occurs with noticeable levels (up to⩾ 45:1) of stereoselection when carried out in the presence of alkaloid derived ligands. Matching and mismatching substrate-ligand pairs have been identified.     

Diastereoselective photodeconjugation of chiral α,β-unsaturated esters

Chiral alcohols available in both enantiomeric forms have been tested for the diastereoselective photochemical deconjugation of 2,4-dimethylpentenoic acid esters. (R)-Pantolactone afforded selectively the (2R)-β,γ-unsaturated ester in good yield and high d.e. (89%), while analogous use of (S)-pantolactone gave the (2S)-stereoisomer with similar selectivity.     

Selective reduction of α,β-unsaturated esters in the presence of olefins

Several α,β-unsaturated esters containing also isolated olefins or other functionalities subject to saturation were selectively reduced to the corresponding saturated esters by magnesium in methanol.     

A very enantioselective photodeconjugation of α,β-unsaturated esters

An enantiomeric excess up to 70% can be obtained in the photodeconjugation of conjugated esters in the presence of (1R, 2S) 1-phenyl, 2-isopropylamino-propanol.     

Rhodium-catalyzed asymmetric addition of arylboronic acids to γ-phthalimido-substituted-α,β-unsaturated carboxylic acid esters: an approach to γ-amino acids

Efficient Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to ethyl-γ-phthalimidocrotonate by using bis-sulfoxide ligand affords γ-aminobutyric acid (GABA) derivatives with high enantioselectivities (90-96% ee) under mild conditions. Optically pure (S)-Baclofen and (S)-Rolipram have been prepared successfully through this synthetic route.     

Efficient Synthesis of Indolizidine Alkaloids from γ-Hydroxy-α,β-unsaturated Sulfones

An efficient and stereoselective synthesis of polyhydroxylated indolizidine alkaloids from readily available N-substituted γ-hydroxyvinyl sulfones is described.     

Addition of alkyllithium and Grignard reagents to tetracarbonyliron complexes of α,β-unsaturated esters

Addition of alkyllithium and Grignard reagents to the tetracarbonyliron complexes of methyl acrylate (1) and methyl crotonate (2) leads to the production of 4-ketoesters via acyl transfer from the metal to the β carbon of the α,β-unsaturated ester.     

Addition of esters of nitroacetic acid to α,β-unsaturated ketones

Summary The addition reaction of esters of nitroacetic acid to, -unsaturated ketones was studied, and new esters of ketonitroacids were prepared.     

SmI2-induced reductive cross-coupling of carbonyl compounds with (α,β-unsaturated esters

Reductive cross-coupling of carbonyl compounds with(α,β-unsaturated esters by SmI₂ to ?-lactones was highly accelerated by the addition of hexamethylphosphoric triamide (HMPA).     

Manganese-catalyzed bicyclic annulations of imines and α,β-unsaturated esters via C-H activation

A manganese-catalyzed bicyclic annulation of imines with α,β-unsaturated esters via C–H activation is described, which provides an expedient access to fused β-lactams in one-step operation with high efficiency and good functional group tolerance. Of note, both ketimines and aldimines are amenable to this transformation. Mechanistic studies have identified a five-membered azamanganacycle as the key reaction intermediate.     

Cyclic acetal formation between 2-pyridinecarboxyaldehyde and γ-hydroxy-α,β-acetylenic esters

A new transformation between 2-pyridinecarboxyaldehyde and γ-hydroxy-α,β-acetylenic esters to form highly functionalized cyclic acetals was discovered. This transformation proceeds under very mild conditions without any additives and is promoted by the basic nature of the pyridine ring.     

Parallel kinetic resolution of acyclic γ-amino-α,β-unsaturated esters: application to the asymmetric synthesis of 4-aminopyrrolidin-2-ones

Conjugate addition of a 50:50 pseudoenantiomeric mixture of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide and lithium (S)-N-3,4-dimethoxybenzyl-N-(α-methylbenzyl)amide to a range of racemic acyclic γ-amino-α,β-unsaturated esters (derived from the corresponding α-amino acids) effects their efficient parallel kinetic resolution, allowing the preparation of enantiopure β,γ-diamino esters. The β,γ-diamino ester products of these reactions are readily converted into the corresponding substituted 4-aminopyrrolidin-2-ones via N-debenzylation and cyclization.     

Synthesis of α,β-unsaturated γ-amino esters with a quaternary center by ruthenium-catalyzed codimerization of N-acetyl α-arylenamines and acrylates

Ruthenium-catalyzed highly selective codimerization of N-acetyl α-arylenamines with ethyl acrylates is reported. This codimerization reaction provides a new efficient method for the synthesis of α,β-unsaturated γ-amino esters with a quaternary center.     

Preparation of α,β-unsaturated esters and amides via external-CO-free palladium-catalyzed carbonylation of alkenyl tosylates

Palladium-catalyzed carbonylation of tosylates with phenyl formate is described. This procedure needs neither external carbon monoxide nor any pressure-resistant apparatus. A variety of cyclic and acyclic alkenyl tosylates can be converted into the corresponding phenyl esters in good yields. Furthermore, this method is effective for the one-pot synthesis of α,β-unsaturated amides.     

Synthesis of α-fluoro-α,β-unsaturated esters monitored by 1D and 2D benchtop NMR spectroscopy

For optimization and control of pharmaceutically and industrially important reactions, chemical information is required in real time. Instrument size, handling, and operation costs are important criteria to be considered when choosing a suitable analytical method apart from sensitivity and resolution. This present study explores the use of a robust and compact nuclear magnetic resonance (NMR) spectrometer to monitor the stereo-selective formation of α-fluoro-α,β-unsaturated esters from α-fluoro-β-keto esters via deprotonation and deacylation in real time. These compounds are precursors of various pharmaceutically active substances. The real-time study revealed the deprotonation and deacylation steps of the reaction. The reaction was studied at temperatures ranging from 293 to 333 K by interleaved one-dimensional ¹H and ¹⁹F and two-dimensional ¹H–¹H COSY experiments. The kinetic rate constants were evaluated using a pseudo first-order kinetic model. The activation energies for the deprotonation and deacylation steps were determined to 28 ± 2 and 63.5 ± 8 kJ/mol, respectively. This showed that the deprotonation step is fast compared with the deacylation step and that the deacylation step determines the rate of the overall reaction. The reaction was repeated three times at 293 K to monitor the repeatability and stability of the system. The compact NMR spectrometer provided detailed information on the mechanism and kinetics of the reaction, which is essential for optimizing the synthetic routes for stepwise syntheses of pharmaceutically active substances.     

Chromium-mediated stereoselective synthesis of carbohydrate-derived (E)-α,β-unsaturated esters or amides

A chromium-mediated novel synthesis of carbohydrate-derived di- and trisubstituted (E)-α,β-unsaturated esters or amides from a range of dichloroesters or amides and a variety of sugar aldehydes is reported. The process took place with total stereoselectivity and in high yields. A mechanism based on a sequential chromium-promoted aldol-type reaction and a completely stereoselective β-elimination reaction is proposed to explain these results.     

Facile syntheses of fluorine-containing α,β-unsaturated acids and esters from 2-trifluoromethylacrylic acid

Various types of fluorine-containing α,β-unsaturated acids and their esters were synthesized from 2-trilfuoromethylacrylic acid as a sole starting material.