Search

A systematic study to assess the contribution of planar and central chirality to the asymmetric induction in the diethylzinc addition to aromatic and aliphatic aldehydes has been carried out using planar chiral quinolinophanylcarbinols ( R p )- 1 and ( R p )- 11 and diastereomeric quinolinophanylcarbinols ( R p , R )- and ( R p , S )- 5 – 8 , exhibiting both planar and central chirality as catalysts. The stereochemistry of the addition process leading to aryl- or 1-alkylpropanols seems to be mostly controlled by the central chirality. Nevertheless, the planar chirality shows a remarkable cooperative effect on the degree of asymmetric induction, which turns out to be positive or negative depending on the configuration of the stereogenic carbon of the catalyst.

Tetraethyl vinylidenebis(phosphonate) (VBP) reacts smoothly with substituted 1,3-dienes at 90-110 degrees C without solvent to give the corresponding cyclohex-3-ene-1,1-bis(phosphonates) in good yields (60-85%). With nonsymmetrically substituted dienes, mixtures of regioisomers are obtained, the regioisomeric ratio being exclusively controlled by electronic effects. Danishefsky's diene allows tetraethyl 4-oxocyclohex-2-ene-1,1-bis(phosphonate) to be obtained in an 81% overall yield after the acid-catalyzed hydrolysis of the Diels-Alder cycloadduct. With 2,3-dimethoxy-1,3-butadiene, a mixture of regioisomeric dimethoxycyclohexene-1,1-bis(phosphonates) is formed by the VBP-catalyzed isomerization of the normal Diels-Alder cycloadduct. The mixture converges into tetraethyl 3,4-dimethoxycyclohex-2-ene-1,1-bis(phosphonate) at prolonged reaction times.

A survey of some recent synthetic approaches to regioselectively fluorinated six member condensed homo- and heteropolycyclic aromatic compounds by complementary cyclization methods is reported.

Accepted Manuscript version. The Published Journal Article is available on the Journal of Chromatography A, Volume 1232, pages 128–133 (DOI: https://doi.org/10.1016/j.chroma.2011.10.090). Supplementary Material available free of charge on the article webpage. © 2011. This Manuscript version is made available under the CC-BY-NC-ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/ ABSTRACT Enantioselective high performance liquid chromatography (HPLC) coupled with a detection system based on the simultaneous measurement of UV absorption and electronic circular dichroism (ECD) allows a complete stereochemical characterization of chiral compounds, once the relationship between sign of the chiroptical properties and absolute configuration is determined. In the present communication, the development of enantioselective HPLC methods for the resolution of a series of fluorinated 2-phenanthrenylpropionic acids (1-6) is reported. Different chiral stationary phases (CSPs) were tested: Chiralcel® OJ, Chiralcel® OD, Chiralpak® AD, (S,S)-Whelk-O® 1, Chirobiotic™ T and α1-acid glycoprotein (AGP). The results allow the application of the methods to a reliable determination of the enantiomeric excess for all the examined compounds; the highest enantioselectivity values were obtained with the Hibar® [(S,S)-Whelk-O® 1] column for some of the examined compounds. In the case of rac-2-(6-fluorophenanthren-1-yl)propionic acid (1), the relationship between circular dichroism and absolute configuration of the enantiomeric fractions was determined by ECD analysis and time-dependent density functional theory (TD-DFT) calculations. The experimental ECD spectrum of the second-eluted fraction of 1 on the Hibar® [(S,S)-Whelk-O® 1] column was found to be in excellent agreement with the theoretical ECD spectrum of (S)-1; therefore, the absolute configuration of the first- and second-eluted enantiomers on the (S,S)-Whelk-O® 1 CSP was assessed as (R) and (S), respectively, and the elution orders of the enantiomeric forms of 1 were determined on all the different CSPs.

1-Oxa-2,3-cyclohexadiene (I) can be readily generated by treatment of 5-bromo-3,4-dihydro-2H-pyran with potassium tert-butoxide in the presence of 18-crown-6 and can be trapped with dienes or olefins. Thus, the treatment of I with furan gave 50% yield of Diels-Alder adduct II, whereas with 1,1-diphenylethylene I gave 43% of the [2+2]cycloadduct III. The remarkable regio- and stereoselectivities with which [4+2] and [2+2] adducts are formed suggests a concerted, non-radical cycloaddn. mechanism. [on SciFinder (R)]

Trimethylsilyl dienol ethers are easily oxidized by ceric ammonium nitrate to give α-carbonylallyl radicals which are able to add to enolic carbon-carbon double bonds with very high γ regioselectivity, allowing the method to be applied to the synthesis of 6-oxo-α,β-unsaturated carbonyl compounds.

At the beginning of this article an in-depth comparison of electrophilic and nucleophilic aromatic and heterocyclic substitution processes examines their scopes of applicability in a new light. In the subsequent parts, recent progress in the area of halide and hydride displacement from pyridines is highlighted. Particular attention is paid to the leaving group aptitudes of fluoride and chloride, to the effect of 'passive' substituents on the reaction rates, and to the control of the relative reactivity at halogen-bearing 4-versus 2-(or 6-)positions.

Organic sulfides are selectively oxidized to the corresponding sulfoxides in high yields and under very mild conditions using 35% hydrogen peroxide in CHCl3 in the presence of catalytic amounts of 1, 1, 1-trifluoroacetone.

The CD spectra of a new series of 4-substituted [2.2]paracyclophanes 1b – e have been measured down to 185 nm. Polarizability calculations within the DeVoe model satisfactorily reproduce the CD features over all the spectral range. In addition, the analysis of the complete CD spectrum allowed a phenomenological interpretation of the dependence of the sign of [α] D on the nature of the substituents, at least for X=F, OH, I.

The synthesis of optically active (+)-(R)-[2.2]paracyclophane-[4,5-d]-oxazol-2(3H)-one is described. The aldol reaction of N-acyl derivatives of this planar chiral auxiliary with beazaldehyde occurs with good diastereo- and enantioselectivity.

Regioselectively fluoro-, trifluoromethyl- and trifluoromethoxy-substituted 3-methyleneindolines have been prepared using a four-step procedure involving metalation/bromination of fluorinated Boc-protected anilines, N -propargylation of the resulting o -bromoarylcarbamate and reductive radical cyclization of the product with tributyltin hydride/AIBN. 3-Methyleneindolines, as valuable, versatile intermediates, can be transformed into highly functionalized 3-substituted indoles by ene-type reactions using different enophiles. Thus, fluoro-, trifluoromethyl- and trifluoromethoxy-substituted diethyl 2-hydroxy-2-[(1 H -indol-3-yl)methyl]malonates, ethyl 2-hydroxy-3-(1 H -indol-3-yl)propionates and ethyl 2-hydroxy-3-(1 H -indol-3-yl)-2-trifluormethylpropionates were obtained in 77–86% yield by simply heating the corresponding tert -butyl 3-methyleneindoline-1-carboxylate with an equimolar amount of diethyl ketomalonate, ethyl glyoxalate and ethyl 3,3,3-trifluoropyruvate, respectively, at 100 °C, without solvent, for 0.5–4 h.

Regioselectively fluorinated 1-(naphth-2-ylmethyl)imidazoles 1a-h have been synthesized starting from the corresponding (naphth-2-yl)methanols (2). 2a-d have been obtained by LiAlH4-promoted reduction of fluorinated 1-methyl-2-naphthaldehydes. The latter were easily prepared in fairly good overall yields by ceric ammonium nitrate (CAN)-promoted oxidative addition of the suitable 3-(fluoroaryl)-1-trimethylsilyloxy-1-butenes to ethyl vinyl ether in methanol followed by cyclization of the resulting acetals in strongly acidic medium in the presence of DDQ. 2e-h were prepared by LiAlH4-promoted reduction of the corresponding fluorinated methyl 2-naphthoates. The latter were more profitably obtained by reacting the suitable benzyl bromide with the sodium salt of dimethyl 2-(2,2-dimethoxyethyl)malonate in DMF followed by demethoxycarbonylation and acid catalysed cyclization of the resulting acetals. Compared with the nonfluorinated parent compounds 1i-1, fluorinated 1-(naphth-2-yl)methylimidazoles 1a-h turned out to be potent inhibitors of CYP17 and CYP19 enzymes. The most active inhibitor of CYP17 is 1c, whereas CYP19 is strongly inhibited by 1b, 1e, and 1g. Interestingly, 1g is a potent dual inhibitor also being very active towards CYP19.

Regioisomerically pure trifluoromethyl- and trifluoromethoxy-substituted aromatic and heteroaromatic aldehydes and carboxylic acids are valuable building blocks for the synthesis of biologically active molecules. They have been prepared by employing modern organometallic methods. On this basis, a novel access to 2,3-dihydro-5-(trifluoromethoxy)indole was developed which represents an intriguing example of how organometallic and radical chemistry can fecundate each other.

Das vollstandige Manuskript dieser Zuschrift erscheint in: Angew. Chem. Suppl. 1982, 1853. DOI: 10.1002/ange.198218530

dibromo-5-chloro-2,3-dihydrobenzofuran and anti eliminations from cis- 2,3-dichloro-2,3-dihydrobenzofuran have been investigated in different base-solvent systems. Anti elimination is favored over the syn by a factor of -33 000 in EtONa-EtOH, -10 000 in t-BuOK-t-BuOH, and >10 000 in t-BuOK-t-BuOH, in the presence of 18-crown-6 ether. The rate of both the anti and syn pathway increases with increasing the medium basicity, the syn path being also favored, however to much less extent, by base association. From the values of the deuterium kinetic isotope effect and substituent effect it can be concluded that the transition state structure for the syn elimination from trans2,3-dibromo-2,3-dihydrobenzofuran is significantly affected by base association, but not by medium basicity. trans-2,3-Dihalogeno-2,3-dihydrobenzofurans are very suitable substrates for the study of elimination processes owing to their tendency to be converted by bases into the aromatic benzofuran system. Recently we have investigated the reactions of trans-2,3-dibromo-2,3-dihydrobenzofuran (I) with bromide and chloride ions in dipolar aprotic so1vents.l With bromide ions I is dehalogenated to benzofuran, whereas with chloride ions it gives mainly trans- 2,3-dichloro-2,3dihydrobenzofuran (11)2 together with ca. 10% of 3-bromobenzofuran presumably formed in a syn dehydrobromination process. Syn dehydrohalogenation, however, is the only reaction observed when I or I1 reacts with an alkoxide in the corresponding alcohol. Owing to the increasing importance of syn elimination reactions, it seemed interesting to carry out a detailed kinetic investigation, including the determination of deuterium kinetic isotope effect and substituent effect of the reactions of I and I1 in different alkali alkoxide-alcohol systems. For comparison purposes some anti eliminations from cis -2,3dichloro-2,3-dihydrobenzofuran (111) have also been studied.3 Results and Discussion The eliminations from 1-111, trans-2,3-dibromo-3-deuterio-2,3-dihydrobenzofuran (IV), and trans-2,3-dibromo5-chloro-2,3-dihydrobenzofuran (V) have been studied in EtOK-EtOH, n-BuOK-n-BuOH, t-BuOK-t-BuOH, nRuOK-18C6-n-BuOH (18C6 is 18-crown-6 ether), and t BuOK-18C6-t-BuOH. Some experiments for the reactions of 1-111 in EtONa-EtOH have been also carried out. In each

Les reactions du titre sont realisees sous diverses conditions: a) reaction avec le nitrate d'ammonium cerique (CAN) dans l'acide acetique et l'acetonitrile aqueux ; b) oxydation electrochimique dans l'acetone aqueuse et dans AcOH−CH 3 CN ; c) autooxydation photochimique en presence d'anthracenedicarbonitrile-9,10 ou CAN dans CH 3 CN ; d) oxydation photochimique par CAN dans CH 3 CN

Les β-eliminations syn et anti a partir d'une serie de 31 dihalogeno-2,3 dihydro-2,3 benzofurannes sont etudiees du point de vue cinetique dans t-BuOK-t-BuOH, en presence et en l'absence de 18-crown-6, et dans EtOK-EtOH

"Isoretinolq I was prepd. in 55% yield by methylation of II, obtained by reaction of III with the (chlorodihydrofuryl)copper IV. Oxidn. of I with Me2SO contg. N,N'-dicyclohexylcarbodiimide gave a stereoisomeric mixt. of retinal. Similarly, Me2C:CHCH2CH2CMe:CHCH:C:CMeCH2CH2OH was prepd. from geranyl bromide and IV and oxidized to give 4,5-dehydrofarnesal, Me2C:CHCH2CH2CMe:CHCH:CHCMe:CHCHO, which was reduced to give 4,5-dehydrofarnesol, Me2C:CHCH2CH2CMe:CHCH:CHCMe:CHCH2OH. [on SciFinder (R)]

1,4-diketones and 4-ketoaldehydes dimethylacetals can be prepared in good yields (65%–82%) by the cerium(IV) ammonium nitrate promoted reaction of ketones with isopropenyl acetate and vinyl acetate, respectively.

Rate ratios were obtained for the base-catalyzed 1,4-dehydrochlorination of (E)- and (Z)-Me3CCCl:C:C:CClCMe3 to give Me3CC.tplbond.CC.tplbond.CCMe3. In the KOMe/MeOH or KOCMe3/Me2SO systems the reactivity of both isomers was similar. With KOCMe3 in Me3COH, THF or C6H6 the 2 isomers exhibited similar reactivity when 18-crown-6 was present, but the E isomer was much more reactive in its absence. These findings suggested a conveyor-belt-type transition state with an aggregate of the base interacting with the H and Cl atoms undergoing elimination. [on SciFinder (R)]