Asymmetric organocatalytic Michael/α-alkylation reaction of α,β-unsaturated aldehyde with chloroacetophenone

Asymmetric organocatalytic Michael/α-alkylation reactions of α,β-unsaturated aldehydes with chloroacetophenones have been developed. The biologically useful cyclopropane motifs were synthesized with high yields and up to >99% ee, >30:1 dr through Jørgensen-Hayashi catalyst under mild conditions.     

Highly efficient metal-free one-pot synthesis of α-aminophosphonates through reduction followed by Kabachnik–fields reaction using three-component system

One-pot synthesis of α-aminophosphonates directly from aryl nitro compounds, aldehydes/ketones, and diethyl phosphite using sodium dithionite through reduction and followed by Kabachnik–Fields reaction under metal-free conditions is reported. The major advantages are excellent yield, high chemoselectivity, neutral reaction medium, and simple experimental procedure. This methodology consists of the following steps: 1) amine formation from nitro compound, 2) imine formation from amine and aldehyde/ketone, 3) phosphate addition to imine.     

Diastereoselective Friedel–Crafts reaction of α-trifluoromethyl imines derived from chiral amines

The Friedel–Crafts reactions of chiral N-(2,2,2-trifluoroethylidene)-1-arylethylamines 1a and 1b with various electron-rich aromatic compounds were examined. The reactions proceeded readily at room temperature in the presence of BF₃·Et₂O. Substituted products 2–12 were obtained in low to very high stereoselectivities (up to 100% d.e.). The absolute configuration of compound 12 was determined by X-ray analysis. Moreover, the chiral auxiliary from compounds 3 and 12 was selectively removed by palladium-catalyzed hydrogenolysis.     

Mesoporous aluminosilicate nanocage-catalyzed three-component coupling reaction: an expedient synthesis of α-aminophosphonates

Here we demonstrate for the first time the synthesis of α-aminophosphonates through the three-component coupling reaction of aldehydes, amines, and diethyl phosphite by using highly acidic 3D mesoporous aluminosilicate nanocage catalyst, which gave excellent yield with a high selectivity in a short reaction time due to its high acidity, 3D pores, and a huge space in the nanocages.     

Microwave activation of an asymmetric Michael reaction: unexpected behaviour of chiral α-alkoxy imines

While it has been previously established that chiral α-alkoxy imines undergo thermal rearrangement at temperatures above 50°C, the microwave activation of the Michael addition between chiral imine 3b and methyl acrylate at 100°C led cleanly to the corresponding Michael adduct 5b without the formation of any rearranged product and with the same regio- and stereoselectivity as the corresponding thermal condensation at 40°C (ee 95%).     

Enantioselective α-alkylation of unsaturated carboxylic acids using a chiral lithium amide

The regio- and stereochemistry of the alkylation of dienediolates from unsaturated carboxylic acids with benzylic halides, which often results in mixtures of isomers, can be controlled by means of changes in the lithium amide, allowing the α-regioisomer to be obtained as the major diastereoisomer. In addition, when chiral amines are used, moderate enantiomeric excesses can be attained.     

Formal synthesis of berkelic acid: a lesson in α-alkylation chemistry

The full details of our enantioselective formal synthesis of the biologically active natural product berkelic acid are described. The insertion of the C-18 methyl group proved challenging, with three different approaches investigated to install the correct stereochemistry. Our initial Horner-Wadsworth-Emmons/oxa-Michael approach to the berkelic acid core proved unsuccessful upon translation to the natural product itself. However, addition of a silyl enol ether to an oxonium ion, followed by a one-pot debenzylation/spiroketalisation/thermodynamic equilibration procedure, afforded the tetracyclic structure of the berkelic acid core as a single diastereoisomer.     

Advantage of in situ generation of N-arylsulfonyl imines from α-amide sulfones in the phase-transfer-catalyzed asymmetric Strecker reaction

Highly efficient, catalytic enantioselective synthesis of N-arylsulfonyl α-amino nitriles from the corresponding α-amido sulfones has been achieved under toluene-aqueous potassium cyanide biphasic conditions using chiral quaternary ammonium iodide (R,R,R)-1 as an effective phase-transfer catalyst. This Strecker synthesis involving the in situ generation of the reactive N-sulfonyl imines is advantageous for the cyanation of the substrates having primary and secondary alkyl substituents.     

An efficient synthesis of β-aminoketone compounds through three-component Mannich reaction catalyzed by calcium chloride

Abstract  

Various β-aminoketones were synthesized in a three-component reaction of ketones, aldehydes, and amines in the presence of calcium chloride as catalyst in ethanol in high yields as compared to other synthetic methods. The advantages of this new method are a short reaction time (2 h), high yields, easy workup, convenience, low cost, and eco-friendly protocol.     

Synthesis of novel α-acyloxycarboxamides containing vinylbis(silanes) through three-component Passerini reactions

A three-component efficient procedure is described for the synthesis of novel α-acyloxycarboxamides containing bis(trimethylsilyl)ethenyl group from 4-[2,2-bis(trimethylsilyl)ethenyl]benzaldehyde, aromatic carboxylic acids and isocyanides, via the Passerini reaction. This reaction proceeds smoothly and cleanly under mild conditions in H₂O and [bmim]BF₄ at room temperature and led to products in good yields. The silylated aldehyde was obtained via Peterson olefination reaction of terephthalaldehyde with tris(trimethylsilyl)methyllithium in THF at 0 °C.     

Catalytic asymmetric α-alkylation of ketones and aldehydes with N-benzylic sulfonamides through carbon-nitrogen bond cleavage

A range of ketones and aldehydes smoothly undergo asymmetric S(N)1 α-alkylation with N-benzylic sulfonamides in the presence of 10 mol % of a chiral imidazolidinone and trifluoroacetic acid to give the corresponding products in good to excellent yields and with good enantioselectivity. This chemistry has been successfully extended to the asymmetric desymmetrization of 4-substituted cyclohexanones, which exhibits greater than 99:1 diastereoselectivity and good enantioselectivity.     

Translocation of α-helix chains through a nanopore

The translocation of α-helix chains through a nanopore is studied through Langevin dynamics simulations. The α-helix chains exhibit several different characteristics about their average translocation times and the α-helix structures when they transport through the nanopores under the driving forces. First, the relationship between average translocation times τ and the chain length N satisfies the scaling law, τ～N(α), and the scaling exponent α depends on the driving force f for the small forces while it is close to the Flory exponent (ν) in the other force regions. For the chains with given chain lengths, it is observed that the dependence of the average translocation times can be expressed as τ～f(-1/2) for the small forces while can be described as τ～f in the large force regions. Second, for the large driving force, the average number of α-helix structures N(h) decreases first and then increases in the translocation process. The average waiting time of each bead, especially of the first bead, is also dependent on the driving forces. Furthermore, an elasticity spring model is presented to reasonably explain the change of the α-helix number during the translocation and its elasticity can be locally damaged by the large driving forces. Our results demonstrate the unique behaviors of α-helix chains transporting through the pores, which can enrich our insights into and knowledge on biopolymers transporting through membranes.     

A highly diastereoselective synthesis of α-hydroxy-β-amino acid derivatives via a Lewis acid catalyzed three-component condensation reaction

A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained in high diastereoselection and yield, was realized starting from an aldehyde, benzylamine, and the ketene silyl acetals derived from Ley's lactones. The synthetic protocol was optimized and the above compounds were obtained without the isolation of intermediates. The origin of the observed diastereoselection was investigated through a computational model of the key reaction step.     

Catalytic asymmetric Mannich reaction of glycine Schiff bases with α-amido sulfones as precursors of aliphatic imines

A general and practical Cu(I)-Fesulphos-catalyzed Mannich reaction of glycinate Schiff bases with aliphatic imines generated in situ from α-amido sulfones is described. Imines with linear and branched alkyl chains, including substrates bearing functional groups, can be efficiently applied. The resulting syn-configured orthogonally protected β-alkyl-α,β-diamino acid derivatives are produced with excellent levels of diastereo- (typically syn/anti >90?:?<10) and enantioselectivity (generally ≥90% ee).     

Intramolecular reaction of polymer coordinated cationic rhodium complex

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Facile,efficient and diastereoselective synthesis of α-hydrazine tetrazoles through a novel one-pot four-component reaction

A novel and efficient method for the diastereoselective synthesis of α-hydrazine tetrazoles via an isocyanide-based multicomponent reaction is reported in good yields. The α-hydrazine tetrazoles were obtained by a facile azide Ugi four-component reaction (U-4CR) using cyclic ketones, trimethylsilyl azide, hydrazides, and corresponding isocyanide without any catalyst and with high bond forming efficiency at room temperature.     

Origins of stereoselectivity in the α-alkylation of chiral hydrazones

Density functional theory calculations and experiment reveal the origin of stereoselectivity in the deprotonation-alkylation of chiral N-amino cyclic carbamate (ACC) hydrazones. When the ACC is a rigid, camphor-derived carbamate, the two conformations of the azaenolate intermediate differ in energy due to conformational effects within the oxazolidinone ring and steric interactions between the ACC and the azaenolate. An electrophile adds selectively to the less-hindered π-face of the azaenolate. Although it was earlier reported that use of ACC auxiliaries led to α-alkylated ketones with er values of 82:18 to 98:2, B3LYP calculations predict higher stereoselectivity. Direct measurement of the dr of an alkylated hydrazone prior to removal of the auxiliary confirms this prediction; the removal of the auxiliary under the reported conditions can compromise the overall stereoselectivity of the process.     

Metal-free one-pot synthesis of quinoline-2,4-carboxylates via a molecular iodine-catalyzed three-component reaction of arylamines,ethyl glyoxylate,and α-ketoesters

A simple and metal-free method has been developed for the construction of quinoline-2, 4-carboxylates under mild conditions via a molecular iodine-catalyzed three-component tandem reaction of arylamines, ethyl glyoxylate, and α-ketoesters. The present protocol provides a convenient and attractive approach to various quinoline-2, 4-carboxylates in moderate to good yields with excellent functional group tolerance.     

Asymmetric additions of α-sulfoxide carbanion on imines

The formation of the anion of methyl p-tolyl sulfoxide was studied in various experimental conditions. This allowed to get a very good control of diastereoselectivity during addition of the above carbanion on many imines. Various stereoisomerically pure aminosulfoxides have been prepared by this approach.     

Asymmetric synthesis of 3-substituted pyrrolidones via α-alkylation of a chiral non-racemic γ-lactam

3-Alkyl pyrrolidones 9 were synthesized in good yield and high diastereoselectivity by α-alkylation of the new chiral non-racemic lactam 8 derived from (R)-(−)-phenylglycinol. After debenzylation and introduction of an electron-withdrawing group, 3-methylpyrrolidone 10 is easily hydrolyzed in a basic medium to produce γ-aminobutyric acid (GABA) analogue 13.