Formation of scalemic α,β-epoxysulfones

This report describes the preparation of optically active α,β-epoxysulfones using an asymmetric phase-transfer catalyzed epoxidation of α,β-unsaturated sulfones.     

Reactions of 2-hydroxyaryl-α,β-unsaturated ketones with dimethylsulfonium carbonylmethylides: a new and facile diastereoselective synthesis of 2,3-disubstituted dihydrobenzofurans

A simple, efficient, and general method has been developed for the diastereoselective synthesis of 2,3-disubstituted dihydrobenzofurans through reactions of 2-hydroxyaryl-α,β-unsaturated ketones with dimethylsulfonium carbonylmethylides.     

Stereoselective synthesis of (Z)-γ-cyano-β-perfluoroalkyl-β,γ-unsaturated esters

(Z)-γ-Cyano-β-perfluoroalkyl-β,γ-unsaturated esters have been synthesized by the reaction of perfluoroacylated phosphonates with organozinc reagent in 50-71% (three steps) yields.     

Catalytic, enantioselective allylation of α-iminoesters promoted by silver(I) complexes of chiral imines

The catalytic enantioselective addition of allyltributylstannane to N-protected α-iminoesters promoted by silver(I) trifluoromethanesulfonate in the presence of chiral imine ligands was studied. After testing several chiral imines derived from 1,2-diaminocyclohexane and binaphthyl diamine a very simple experimental procedure was developed that allowed us to obtain optically active homoallylic amines in very high yields and enantioselectivities up to 71%.     

Formal Synthesis of (+)-Altholactone by Stereoselective Epoxidation Using Magnesium Monoperoxyphthalate (MMPP)

( + ) Ａｌｔｈｏｌａｃｔｏｎｅ ,ａｍｅｍｂｅｒｏｆｎｅｗｔｙｐｅｏｆｃｙｔｏ ｔｏｘｉｃｎａｔｕｒａｌｓｔｙｒｙｌｌａｃｔｏｎｅ ,ｈａｓｂｅｅｎｋｎｏｗｎｔｏｐｏｓｓｅｓｓａｎｔｉｔｕｍｏｒａｃｔｉｖｉｔｙａｇａｉｎｓｔｍｕｒｉｎｅＰ338ｌｅｕｋｅｍｉａａｎｄｓｈｏｗｌｅｔｈａｌｉｔｙｔｏｂｒｉｎｅｓｈｒｉｍｐ .1Ｒｅｃｅｎｔｌｙ ,ａｒｅｐｏｒｔｏｎｉｔｓｓｔｒｕｃ ｔｕｒｅ ａｃｔｉｖｉｔｙｒｅｌａｔｉｏｎｓｈｉｐ2 ａｎｄｐａｐｅｒｓｏｎｔｈｅａｐｐｌｉｃａｔｉｏｎｏｆｎｅｗｓｙｎｔｈｅｔｉｃｍｅ…     

Quinoline-pyrimidine hybrid compounds from 3-acetyl-4-hydroxy-1-methylquinolin-2(1H)-one: Study on synthesis,cytotoxicity, ADMET and molecular docking

Some novel 2-amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-2′-on-3′-yl)pyrimidines have been synthesized from α,β-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding α,β-unsaturated ketones with guanidine hydrochloride. The purity and structure of the obtained products have been confirmed by thin layer chromatography, IR, ¹H NMR, ¹³C NMR, HSQC, HMBC and MS spectra. All the synthesized of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1-methylquinolin-2(1H)-ones 6a-i were screened for their in vitro cytotoxic activity against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC₅₀ values equal to 1.33 μM. Compounds 6a-g exhibited weak or insignificant activity with liver cancer cell lines HepG2, while compounds 6a and 6g had more powerful activity in this sequence, with IC₅₀ values equal to 47.99 and 89.38 μM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f possessed the drug-likeness behavior. Cross-docking results indicated that two hydrogen bonding interactions in the binding pocket, as potential ligand binding hot-spot residues for compounds 6b and 6e, may be one of the mechanisms of action responsible for the higher cytotoxic effect on HepG2 and KB cells.     

Highly stereoselective synthesis of C-(alkynyl)-pseudoglycals from δ-hydroxy-α,β-unsaturated aldehydes

An efficient and novel methodology for the synthesis of C-(alkynyl)-pseudoglycals from δ-hydroxy-α,β-unsaturated aldehydes has been developed.     

Syntheses of 1,5-Benzothiazepines-Part XXXI: Syntheses and Antimicrobial Studies of 10-Substituted-7- (monochlorophenyl/dichlorophenyl)-6H-6a,7-dihydro-6-phenyl[1]benzopyrano[3,4-c]-[1,5]benzothiazepines

Abstract

Two flavindogenides, 3-(2-chlorobenzylidene)-flavanone and 3-(2,4-dichloro- benzylidene)-flavanone reacted with six 5-substituted-2-aminobenzenethiols, the substituents being fluoro, chloro, bromo, methyl, methoxyl, and ethoxyl, to give respective 12 new compounds, 10-substituted-7-(2-chlorophenyl/2,4-dichlorophenyl)- 6H-6a,7-dihydro-6-phenyl[1]benzopyrano[3,4?c][1,5]benzothiazepines (5a–l) in 60–70% yields. The products were characterized on the basis of microanalytical data for elements and IR, ¹ H, and ¹³ C NMR and mass spectral studies. All the synthesized compounds were evaluated for their antimicrobial activity against the bacteria,Escherichia coli and GFC,and the fungi,Aspergillus niger, Aspergillus flavus,and Curvularia lunata.     

Synthesis of new C1-symmetric bis(oxazoline) ligands with a chelating sidearm for stereoselective Mukaiyama aldol condensations

Novel C₁-symmetric bis(oxazoline) ligands with a secondary binding sidearm were prepared in enantiomerically pure form in good yields, in only four steps starting from commercially available reagents. These new chiral ligands were tested in the enantioselective Mukaiyama aldol condensation between the trimethylsilyl keteneacetal of methyl isobutyrate and a non-chelating substrate such as benzaldehyde to afford the product in up to 55% ee.     

Efficient Protocol for Stereoselective Epoxidation of Cinnamic Esters Using TsNBr2

An efficient method has been developed for the synthesis of epoxide from cinnamic esters without any catalyst. The reaction was performed in CH₃CN–water (4:1) using N,N-dibromo-p-toluenesulfonamide (TsNBr₂) in alkaline conditions. This procedure can be utilized for stereoselective synthesis of epoxides from cinnamic esters in excellent yield in a shorter reaction time with exclusive formation of the trans-isomer. The method was further extended successfully for styrenes.     

Stereoselective synthesis of (Z)-β-fluoro-α,β-unsaturated esters from (Z)-2-fluoro-1-alkenyliodonium salts

(Z)-β-Fluoro-α,β-unsaturated esters were stereoselectively synthesized from (Z)-2-fluoro-1-alkenyliodonium salts by the Pd-catalyzed methoxycarbonylation reaction. The reaction proceeded at room temperature and various functional groups on the substrate can tolerate the reaction conditions.     

Synthesis, characterization, and catalytic application of a new chiral P,N-indene ligand derived from (R)-BINOL

Lithiation of 2-dimethylaminoindene followed by quenching with [(R)-(1,1′-binaphthalene-2,2′-diyl)]chlorophosphite and treatment with triethylamine afforded the crystallographically characterized enantiopure P,N-indene 3 in 71% isolated yield. In the course of rhodium coordination chemistry studies involving 3, the formation of the isolable complex [(κ²-P,N-3)(κ¹-P,N-3)RhCl] (7) (81%) was observed, thereby confirming the propensity of this new ligand to form L_nRh(3)₂ complexes. Such coordination chemistry behavior may contribute in part to the generally poor catalytic performance exhibited by mixtures of 3 and rhodium precursor complexes in the asymmetric hydrogenation and hydrosilylation studies described herein.     

Asymmetric Reduction of Ketones with Catecholborane Using 2,6-BODOL Complexes of Titanium(IV) as Catalysts

Reductions performed with Ti^IV complexes of ligands based on bicyclo[2.2.2]octane diols 5 and 6 are effective catalysts in the reduction of prochiral ketones to optically active alcohols, with catecholborane as the reducing agent. Methyl ketones are favored and enantiomeric excesses (ee) of ≤98 % have been achieved with acetophenone as the substrate. Several other substrates were tested, among them 2-octanone, which gave 2-octanol in 87 % ee. Further details of the method were examined, for example, temperature, solvent composition, amount of molecular sieves (4 Å), and catecholborane quality, as well as the sensitivity of the ligands towards acids. NMR spectroscopic methods were used to gain some insight into the complexes formed between the ligands and [Ti(OiPr)₄]. A dimeric structure is proposed for the pre-catalyst.     

二(N-十二烷基-N,N-二羧甲基铵基)-联苯二苄的合成

在氯乙酸钠存在下,二(N-十二烷基)-联苄胺经N-烷基化反应合成了新型双子表面活性剂——二(N-十二烷基-N,N-二羧甲基铵基)-联苯二苄(1)。1的结构经IR确证。     

Synthetic application of fluorinated vinamidinium salts: Synthesis of fluorinated 1,3-butadienylphosphonates by the reaction with Horner-Wadsworth-Emmons reagents

The reaction of β-fluoro vinamidinium salt 1 with Horner-Wadsworth-Emmons reagents (HWE) such as diethyl(ethoxycarbonyl)methylphosphonate (2a), diethyl(methoxycarbonyl)methylphosphonate (2b), diethyl-2-oxopropylphosphonate (2c), diethyl benzylphosphonate (2d), tetraethyl methylenediphosphonate (2e) and diethyl cyanomethylphosphonate (2f) under basic conditions gave the fluorinated 1,3-butadienylphosphonates 3 in moderate to good yields. The phosphonates 3 could be hydrolyzed with a 10% HCl aqueous solution to afford the corresponding γ-(diethylphosphono)-α-fluoro-α,β-unsaturated aldehydes 7 in good yields. The treatment of the phosphonate 3c with an NH₃ aqueous solution at 70 °C produced the pyridine derivative 8 in 60% yield.     

Sequential Iron-Catalyzed C(sp2)–C(sp3) Cross-Coupling of Chlorobenzamides/Chemoselective Amide Reduction and Reductive Deuteration to Benzylic Alcohols

Benzylic alcohols are among the most important intermediates in organic synthesis. Recently, the use of abundant metals has attracted significant attention due to the issues with the scarcity of platinum group metals. Herein, we report a sequential method for the synthesis of benzylic alcohols by a merger of iron catalyzed cross-coupling and highly chemoselective reduction of benzamides promoted by sodium dispersion in the presence of alcoholic donors. The method has been further extended to the synthesis of deuterated benzylic alcohols. The iron-catalyzed Kumada cross-coupling exploits the high stability of benzamide bonds, enabling challenging C(sp²)–C(sp³) cross-coupling with alkyl Grignard reagents that are prone to dimerization and β-hydride elimination. The subsequent sodium dispersion promoted reduction of carboxamides proceeds with full chemoselectivity for the C–N bond cleavage of the carbinolamine intermediate. The method provides access to valuable benzylic alcohols, including deuterium-labelled benzylic alcohols, which are widely used as synthetic intermediates and pharmacokinetic probes in organic synthesis and medicinal chemistry. The combination of two benign metals by complementary reaction mechanisms enables to exploit underexplored avenues for organic synthesis.     

Highly Efficient One-Pot Synthesis of N-Alkyl Sulfonamides from Alcohols Using N-(p-Toluenesulfonyl) Imidazole (Tsim)

Abstract

A facile and efficient method for one-pot synthesis of N-alkyl sulfonamides from alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this protocol, treatment of various potassium sulfonylamide salts and alcohols in the presence of TsIm and triethylamine in refluxing DMF furnishes the corresponding N-alkyl sulfonamides in good to excellent yields. This methodology is highly efficient for reaction of various structurally diverse primary and secondary alcohols as well as potassium sulfonylamides. Also, the density functional theoretical calculations are employed to mechanistically study this protocol.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]     

Tandem reduction-olefination for the stereoselective synthesis of (Z)-α-fluoro-α,β-unsaturated esters

A tandem stereoselective reduction-olefination reaction of ethyl 2-acyl-2-fluoro-2-diethylphosphonoacetate employing NaBH₄ in EtOH was developed. The one-pot reaction gave α-fluoro-α,β-unsaturated esters with excellent (Z)-selectivity. A plausible mechanism involving a diastereoselective reduction predicted by the Felkin-Anh model, followed by olefination similar to the Horner-Wadsworth-Emmons reaction, has been proposed.