A new strategy for the synthesis of chiral β-alkynyl esters via sequential palladium and copper catalysis

A new strategy for the synthesis of chiral β-alkynyl esters which relies on sequential Pd and Cu catalysis is reported. Terminal alkynes bearing aryl, alkyl, and silyl groups can be employed without prior activation yielding a wide range of important chiral building blocks. The reaction sequence utilizes a robust Pd(II)-catalyzed hydroalkynylation of ynoates with terminal alkynes providing geometrically pure ynenoates which are readily reduced by CuH. In contrast to previous reports, where additions to ynenoates proceed with marginal preference for the 1,6-pathway, this conjugate reduction occurs with high 1,4-selectivity yielding β-alkynyl esters with excellent levels of enantioselectivity. Importantly, the method tolerates a wide range of functionality, including allylic carbonates and carbamates, and thus allows for rapid elaboration of the β-alkynyl esters into a variety of chiral, substituted heterocycles.     

Enantioselective total synthesis and studies into the configurational stability of bismurrayaquinone a

Lost in rotation: The concise strategy of the first enantioselective total synthesis of bismurrayaquinone?A utilized traceless stereochemical exchange to form an enantioenriched biphenyl core that was elaborated in a bidirectional manner to the natural product. Observed racemization on an unsuccessful initial route prompted studies into the configurational stability of bismurrayaquinone?A and related biquinones.     

The design and synthesis of a novel organophosphorus compound containing the structure of both β-amino acid and β-aminophosphonate

<正>A novel organophosphorus compound containing the structure of bothβ-amino acid andβ-aminophosphonate is designed and synthesized.Arbuzov reaction with P(OEt)_3,the N-Boc protected iodide 3 cannot provide the desired product but 2-oxazolidinone 4 because of the neighboring-group participation of the Boc moiety.To avoid the intramolecular participation of the carbamates,the Ts protecting group is employed and the Ts-protected iodide 5 affords the target product successfully.     

Inclusion complexes of β-cyclodextrin with pyrazinamide and piperazine: Crystallographic and theoretical studies

The inclusion complexes of β-cyclodextrin (β-CD) with pyrazinamide (PYA) and piperazine (PIZ) have been investigated both in the solid phase by single-crystal X-ray diffraction analysis and in the gas phase by semi-empirical PM3 calculation. In the crystalline phase, the disordered PYA and PIZ molecules are entirely embedded in the β-CD cavity. The PYA pyrazine-centre displaces upwards by 1.15(1) Å from the β-CD plane, whereas the PIZ centre shifts downwards by 0.76(1) Å from the β-CD plane. The inclusion scenario changed in the gas phase. Two inclusion geometries of the PYA molecule are comparatively stable with binding energies of ? 22.28 and ? 25.29 kJ mol^? 1: the pyrazine centre shifts upwards by 0.5 Å and downwards by 2.0 Å from the β-CD plane. The PIZ molecule positioning at 2.0 Å below the β-CD plane gives a more stable inclusion complex than does the PYA molecule by 22–25 kJ mol^? 1.

Structural distinction of the β-CD–PYA and β-CD–PIZ inclusion complexes in the solid phase (by X-ray crystallography) and gas phase (by PM3 calculation) is a paradigm of the CD conformational flexibility, the induced-fit mechanism and the dynamics of the inclusion process.     

Organocatalytic preparation of simple β-hydroxy and β-amino esters: low catalyst loadings and gram-scale synthesis

A combined amino- and N-heterocyclic carbene (NHC)-catalyzed one-pot reaction sequence for the synthesis of simple enantioenriched β-hydroxy and β-amino esters using commercially available catalysts at low catalyst loadings has been developed. The desired products were obtained in high yield and excellent enantiopurity. The generation of quaternary stereocenters and application in gram-scale synthesis were also realized, with no requirements of inert or anhydrous reaction conditions, thus making this transformation a highly practical protocol.     

A new method for the synthesis of β-halonitroalkanes

Summary A new method is elaborated for the synthesis of -chloronitroalkanes; it consists in the reaction of phosphorus pentachloride with acetals obtained by the addition of primary -nitro alcohols to vinyl alkyl ethers.     

Biological studies and computational modeling of two new copper complexes derived from β-diketones and their nano-complexes

Abstract

The present study was conducted to design and develop new complexes and their metal-based nanodrug (registered as Casiopeínas^® for cancer) with a low toxicity, high efficiency, and high selectivity. First, complexes ([Cu(TTA)(bpy)₂] (1) and [Cu(TTA)₂(en)] (2) (TTA = 4,4,4-trifluoro-1-(2-furyl)-1,3-butanedione) were synthesized and characterized by X-ray diffraction studies, CHN analysis, conductivity measurements, FT-IR and UV-vis spectroscopy. Second, nanoparticles (NPs) of 3 and 4 with the average size of 63.04 and 85.39?nm were prepared with ultrasound. Scanning electron microscopy patterns of 3 and 4 showed irregular spherical and nanorod particles with spongy surface. Furthermore, the anticancer properties of compounds and nano-compounds were studied in MKN-45 cell line. Then, apoptosis studies were carried out utilizing AO/EB staining methods. Finally, to confirm the in vitro experimental data, the theoretical study was carried out by molecular docking studies. The results of DNA docking analysis revealed that 1 and 2 were inserted with DNA via the minor groove. The binding affinity monitors the order of 1?>?2, with a preference of binding to A-T over G-C base pairs sequences.     

Extended Dötz-like cyclization reactions towards the synthesis of eight-membered ring-containing polycycles: scope and theoretical studies

The reaction between cyclobutene-containing dienyl Fischer carbene complexes (FCCs) and alkynes has been studied from both an experimental and a theoretical point of view. We have found that the reaction follows different pathways depending on the nature of the terminal double bond of the carbene complex. Thus, eight-membered carbocycles have been obtained from an extended D?tz-like reaction of dienyl FCCs and indolyl- or benzofuryl-substituted alkenyl FCCs. On the other hand, phenyl- and naphthyl-substituted alkenyl FCCs follow a typical benzannulation pathway giving rise to cyclohexadienones. DFT calculations have allowed us to formulate detailed mechanistic proposals and to provide an explanation for the formation of either the benzannulation products or the eight-membered carbocycles.     

MNBA-mediated β-lactone formation: mechanistic studies and application for the asymmetric total synthesis of tetrahydrolipstatin

Various β-lactones were prepared from β-hydroxycarboxylic acids by intramolecular dehydration condensation using MNBA, an effective coupling reagent, along with a nucleophilic catalyst. The transition state that provides the desired 4-membered ring model system is disclosed by density functional theory (DFT) calculations, and the structural features of the transition form are discussed. This method was successfully applied to the asymmetric total synthesis of tetrahydrolipstatin (THL), an antiobestic drug used in clinical treatment to inhibit the activity of pancreatic lipase.     

A new strategy for the preparation of heterocyclic β-amino esters: orthogonally protected β-amino esters with a piperidine skeleton

A simple strategy is presented for the introduction of a nitrogen atom into the carbocycle of an aminocyclopentenecarboxylic ester via dihydroxylation of the olefinic bond, followed by NaIO₄-mediated cleavage of the diol intermediate and ring expansion, resulting in new regioisomeric 3-amino-4-piperidinecarboxylic acid derivatives. This method permits the preparation of amino esters with a piperidine skeleton in enantiomerically pure form.     

An improved procedure for the two carbon homologation of esters to α, β-unsaturated esters

Treatment of esters with diisobutylaluminum hydride (DIBAL) in the presence of lithio-trialkylphosphonoacetate results in improved yields of the homologated α, β-unsaturated esters. The problematic overreduction, which has previously observed in the half reduction of esters using DIBAL, is minimal (<3%) under these conditions.     

A new synthesis of β,γ-unsaturated esters and allenic esters with construction of a carbon-carbon bond between α- and β-positions by the reaction of magnesium alkylidene carbenoids with lithium ester enolates

Treatment of lithium ester enolates with magnesium alkylidene carbenoids, generated from 1-chlorovinyl p-tolyl sulfoxides with isopropylmagnesium chloride via the sulfoxide-magnesium exchange reaction, gave β,γ-unsaturated esters in moderate to good yields. When this reaction was conducted with the lithium ester enolates of α-chlorocarboxylic acid esters, allenic esters were obtained. This procedure provides an unprecedented way for the synthesis of β,γ-unsaturated esters and allenic esters from ketones with the construction of a carbon-carbon bond between α- and β-positions.     

Ruthenium carboxylate complexes as easily prepared and efficient catalysts for the synthesis of β-oxopropyl esters

The easily prepared complex cis-[Ru(κ²-O₂CMe)₂(PPh₃)₂] is an effective catalyst for the addition of carboxylic acids to propargyl alcohols to afford β-oxopropyl esters. The reaction is tolerant to a range of functional groups on the propargyl alcohol and is effective in the case of the steroid ethisterone. An investigation into the ruthenium-containing products from the reaction involving benzoic acid revealed that rapid exchange between coordinated acetate and benzoate ligands occurs. The synthesis of crystallographically characterised cis-[Ru(κ²-O₂CPh)₂(PPh₃)₂] was developed. This benzoate-substituted complex was shown to react with HCCPh and HCCC(OH)PhH to give [Ru(κ²-O₂CPh)(κ¹-O₂CPh)(CCPhH)(PPh₃)₂] and [Ru(κ²-O₂CPh)(κ¹-O₂CPh)(CCC{OH}PhH)(PPh₃)₂] respectively. Reaction of cis-[Ru(κ²-O₂CPh)₂(PPh₃)₂] with CO affords [Ru(κ²-O₂CPh)(κ¹-O₂CPh)(CO)(PPh₃)₂] or [Ru(κ²-O₂CPh)₂(CO)₂(PPh₃)₂] depending on the conditions employed. Related carbonyl compounds are thought to be the ruthenium-containing products from the catalytic reactions and [Ru(κ²-O₂CMe)(κ¹-O₂CMe)(CO)(PPh₃)₂] was also shown to be a competent catalyst.     

Stereocontrolled reduction of chiral pyrrolidine and piperidine β-enamino esters: formal enantioselective synthesis of (+)-calvine

The results of a study dealing with the chemio- and diastereoselective reduction of chiral pyrrolidine and piperidine β-enamino esters 1, 2 and 3, 4 into β-amino esters are reported. This approach was successfully applied to a formal synthesis of (+)-calvine.     

Silicon-containing esters of α-cyanoacrylic acid: synthesis and properties

A number of cyanoacetates have been synthesized: cyanoacetoxymethyitrimethylsilane (1), cyanoacetoxymethylpentamethyldisiloxane (2), cyanoacetoxyetoxymethylpentamethyldisiloxane (3). They were converted by the Knoevenagel reaction to novel esters of a-cyanoacrylic acid (4–13) containing silicon atoms in the ester groups and having the general formula RCH=C(CN)COOCH₂X (where R=H, 4-MeOC₆H₄, MeCH=CH, 2-furyl; X=SiMe₃, SiMe₂OSiMe₃, CH₂OCH₂SiMe₂OSiMe₃). These compounds are capable of copolymerization with esters of cyanoacrylic acid which are the precursors to adhesives for cold curing.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 949–952, May, 1993.     

A facile method for the synthesis of enantiopure α-unsubstituted β-hydroxy esters

One-pot deacylation–debromination reactions involving the transesterification of the initial chiral α-bromo-β-hydroxy thioimide aldol adducts and subsequent Al–Hg mediated reductive cleavage of the C–Br bond allow for a facile synthesis of enantiopure β-hydroxy esters.