Aluminum-catalyzed asymmetric alkylations of pyridyl-substituted alkynyl ketones with dialkylzinc reagents

Alkylations of pyridyl-substituted ynones with Et2Zn and Me2Zn, promoted by amino acid-based chiral ligands in the presence of Al-based alkoxides, afford tertiary propargyl alcohols efficiently in 57% to >98% ee. Two easily accessible chiral ligands are identified as optimal for reactions of the two dialkylzinc reagents. Catalytic alkylations with Et2Zn require a chiral ligand carrying two amino acid moieties (valine and phenylalanine) along with a p-trifluoromethylphenylamide C-terminus. In contrast, reactions with Me2Zn are most effectively promoted in the presence of a chiral ligand containing a single amino acid (benzyl cysteine), capped by an n-butylamide. Enantiomerically enriched tertiary alcohols bearing a pyridyl and an alkyne substituent can be functionalized in a variety of manners to furnish a wide range of difficult-to-access acyclic and heterocyclic structures; two noteworthy examples are Cu-catalyzed protocols for conversion of tertiary propargyl alcohols to enantiomerically enriched tetrasubstituted allenes and bicyclic amides that bear an N-substituted quaternary carbon stereogenic center. Mechanistic models that account for the trends and enantioselectivity levels are provided.     

Keto-enol and enol-enol tautomerism in trifluoromethyl-β-diketones

The keto-enol (K?E) and enol-enol (E?E) equilibria of a variety of trifluoromethyl-β-diketones were investigated using ¹H, ¹³C, ¹⁹F NMR spectroscopy, infrared spectroscopy and ultraviolet-visible spectrophotometry in nonpolar solvents. In general, NMR, IR and UV spectral evidence indicates that trifluoromethyl-β-diketones exist as mixtures of two chelated cis-enol forms in nonpolar media. Infrared spectroscopy and ultraviolet spectrophotometry show the E?E equilibrium lies in the direction of the enol form which maximizes conjugation in most cases. Exceptions are noted and discussed.     

Force field studies of some trifluoromethyl- and trichloromethyl-mercury-II) compounds

Force constants of [Hg(CF₃)₂], [Hg(CCl₃)₂], [Hg(CF₃)X] (X = Cl, Br, or I) and [Hg(CCl₃)X] (X = Cl or Br) have been calculated using a valence force field and wavenumber data from solutions. The potential energy distributions show substantial mixing between the symmetrical stretching and umbrella deformation coordinates of the trihalomethyl groups. The high degree of mixing of HgC and HgX stretching coordinates in [Hg(CF₃)Br] and [Hg(CF₃)I] accounts for the discontinuous frequency and intensity trends in the [Hg(CF₃)X] series.The results are discussed in comparison with methylmercury and other trifluoromethyl systems.     

A novel class of tunable zinc reagents (RXZnCH2Y) for efficient cyclopropanation of olefins

A class of zinc reagents (RXZnCH(2)Y) generated with an appropriate organozinc is very effective for the cyclopropanation of olefins. The reactivity and selectivity of these reagents can be regulated by tuning the electronic and steric nature of the RX group on Zn. A reasonable level of enantioselectivity was obtained for the cyclopropanation of unfunctionalized olefins when a chiral (iodomethyl)zinc species was used, providing a valuable approach for the asymmetric cyclopropanation of unfunctionalized olefins.     

One-pot synthesis of trifluoromethyl- and nitroso-substituted pyrazolines and pyrazoles and their tuberculostatic activity

3-Trifluoromethyl-substituted 4-nitrosopyrazolines and 4-nitrosopyrazoles were prepared by a one-pot synthesis from trifluoromethyl-containing 1,3-diketones, sodium nitrite in acetic acid, and hydrazines (hydrazine hydrate, methylhydrazine). 3-Trifluoromethylpyrazolines can be converted to pyrazoles on heating. The use of phenylhydrazine in these reactions led to the formation of regioisomeric 4-hydroxyimino-5-(trifluoromethyl)pyrazoline. The structure of heterocycles synthesized was established using X-ray diffraction study, ¹H and ¹⁹F NMR spectroscopy. The obtained products exhibited considerable tuberculostatic activity.     

Aluminum-catalyzed efficient synthesis of anilides by the acylation of aryl amines under ultrasonic conditions

Abstract

Substituted aryl amines undergo smooth acylation with different acyl chlorides to give anilides under sonic condition (35 kHz, 25°C) in the presence of catalytic amounts of aluminum metal powder in acetonitrile as solvent. All the reactions go to completion within 4 min and give the products in high yields (85–97%).

     

Enantioselective organocatalytic route to trifluoromethyl-β-amino acids using chiral bases

Herein are studied new aspects of enantioselective (1,3) proton transfer of ethyl-4,4,4-trifluoroacetoacetate (ETFAA) amino derivatives. When catalyzed by an appropriate chiral base, ee's as high as 71% are observed. Special emphasis is given to mechanistic insights of the reaction by use of deuterated derivative. All results converge on a deprotonation as both rate and asymmetric determining step. This study opens a new route to trifluoromethylated chiral building blocks.     

Synthesis of trifluoromethyl-/cyclopropyl-substituted 2-isoxazolines by DBU-promoted domino reaction

NTrifluoromethyl and cyclopropyl substituted 2-isoxazolines were synthesized via a DBU-promoted domino reaction of β-trifluoromethyl-/β-cyclopropyl-substituted enones with hydroxylamine. The domino reaction consists of a Michael addition and the followed cyclization. A wide range of 3-substituted 5-cyclopropyl-5-trifluoromethyl-2-isoxazolines were obtained in good to excellent yields under mild reaction conditions. The method could also apply to other trifluoromethyl-substituted enones.     

1,8-Naphthyridines. Part I. Synthesis of some trifluoromethyl-1,8-naphthyridine derivatives

The synthesis of some 2-amino-1,8-naphthyridine derivatives substituted in the 5- and/or 7-positions with trifluoromethyl is described along with their conversions to the corresponding 1,8-naphthyridin-2(1H)ones. A modified procedure for oxidizing electron-deficient heterocyclic compounds to their N-oxides is presented.     

Fluorinated olefins and oleum

Oleum has some advantages over pure sulfur trioxide and may be successfully used for preparation of beta-sultones from hexafluoropropene, 2H-pentafluoropropene, 6H-perfluoro-1-hexene and perfluoro(propylvinyl) ether (VE). Depending on the reaction conditions, the VE-sultone and tetrafluoroethane-beta-sultone (TFE-sultone) are different from other sultones. They are not stable in the presence of oleum and the oxidation of -CF₂-SO₂-group in the sultones leads to some new fluorooxalate derivatives.     

Bromo-boronolactonization of olefins

Exposure of a variety of mono- and disubstituted ortho-alkenylarylboronic acids to NBS in THF/H(2)O under neutral conditions affords bromo-boronolactones, in some instances, with exceptional regiocontrol. The adducts, analogous to those formed by carboxylic acids, are shown to be useful synthetic intermediates.     

Synthesis and structures of trifluoromethyl-, fluoro-, and azido-substituted hexabenzylhexaazaisowurtzitanes and isolation of a novel hexaazaisowurtzitane-based polycycle

The first hexabenzylhexaazaisowurtzitane cage compounds with trifluoromethyl and azide groups, as well as those with fluorine atoms in the 3- and 4-positions, have been prepared and fully characterized. A study of the substituent influence on the benzene ring regarding the formation of the hexaazaisowurtzitane polycycle in either the 2- or 4-position with CF(3), F, and N(3) revealed an interesting difference. In all cases with CF(3), F, and N(3) substituents in the 4-position, the corresponding hexabenzylhexaazaisowurtzitanes were isolated. The corresponding hexabenzylhexaazaisowurtzitanes were also formed when these substituents were in the 2-position; however, in addition with azide in 2-position a novel type of polycycle was isolated and identified. (15)N NMR data and crystal structures of hexabenzylhexaazaisowurtzitane derivatives were obtained and are discussed in detail.     

Free-radical carboalkynylation and carboalkenylation of olefins

Free-radical three-component carboalkynylation and -alkenylation of olefins have been developed. These involve the addition, across the double bond of an unactivated olefin, of a radical species α- to an electron-withdrawing group and an alkenyl or alkynyl moiety, derived from the corresponding sulfones.