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By making use of a novel diastereotopicity probe, namely C(CF(3))(2)OH, it has been possible to measure by very low temperature (19)F NMR spectroscopy the elusive aryl-aryl rotation barriers of biphenyls bearing an OH or F group in one ortho position. The experimental values (5.4 and 4.4 kcal mol(-1), respectively) are matched by those from ab initio calculations (5.3 and 4.3 kcal mol(-1), respectively).

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.

The size of a series of typical substituents has been probed by dynamic NMR measurements of the barriers to aryl-aryl rotation of the corresponding biphenyls. The resulting B values are meaningful because only mono-ortho substituted compounds were investigated and thus the results are not compromised by the non-additivity of multiple steric effects. On the basis of the chosen model system ethynyl and cyano groups were found to be slightly smaller than a phenyl ring. In contrast, vinyl and, in particular, formyl groups proved to be larger than phenyl. The latter difference is due to the loss of conjugation forces at the planar transition state. Alpha-Hydroxyhexafluoroisopropyl is slightly more bulky than tert-butyl. Pentafluorophenyl and trifluoromethoxy exhibit nearly the same effective size as phenyl and methoxy, respectively. Trifluoromethyl is somewhat smaller than isopropyl.

The role of stereoelectronic effects in the side-chain bromination of alkylaromatics has been assessed by a product study of the reactions of p-ethyltoluene, p-neopentyltoluene, 5,6-dimethylindane and 2,2,5,6-tetramethylindane with NBS in CCl4

A new chiroptical compound, (E)-(R(p),R(p))-1,2-bis{4-methyl-[2]paracyclo[2](5,8)quinolinophan-2-yl}ethene (trans-RPQE) has been synthesized, and its photoresponse has been investigated through steady state and time-resolved absorption and emission spectroscopies and theoretical calculations. To elucidate the relaxation mechanism of trans-RPQE after photoexcitation, the photophysics of the 2,4-dimethyl-[2]paracyclo[2](5,8)quinolinophane chromophore has also been studied. The quantum yields of the different relaxation paths for trans-RPQE have been determined. It emerges that in addition to thermal and radiative routes, trans-RPQE also photoisomerizes with a quantum yield of 8%. Trans- and cis-RPQE isomers are pseudoenantiomers exhibiting appreciably different CD spectra, whereby RPQE can be a model for the design of new promising chiroptical photoswitches.

The addition reactions of 1,3-dicarbonylalkyl radicals to ring-substituted styrenes have been kinetically investigated in MeOH and/or MeCN. It ha^ been observed that the rate effect of ring substituenta ie nearly identical in the reactions of MeCOCHCOMe (11, MeOCOCHCOMe (2) and MeOCOCHCOOMe (4, the p value, in MeOH being 4.96, -1.01 and -1.06, respectively. Since the three radicals are relatively strong oxidants and have similar reduction potentials, an important contribution of the charge transfer structure RCOCHCORCH&HAf+ to the addition transition state is suggested. It has also be found that in the reactions of 1 and 4 with a-alkyl-substituted styrenes the rate of addition is strongly influenced by the nature of the alkyl group, decreasing in the order: Me > Et > 'Pr > tBu. The observed effecta are much larger than those reported for the corresponding reactions of the nucleophilic cyclohexyl radical. It is suggested that the a-alkyl substituents exert an effect of steric inhibition of resonance thereby ring delocalization of the charge and/or unpaired electron in the transition state is significantly reduced. Delocalization may be more important in the reactions of 1 and 4 than in those of the cyclohexyl radical since it is possible that the former utilizes a transition state occurring later along the reaction coordinate and/or characterized by a larger extent of charge transfer.

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)]

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 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.

The relative rates for the addition reactions of the malonyl radical to substituted styrenes induced by cerium(IV) ammonium nitrate (CAN) and tributyltin hydride have been determined. The two processes exhibit practically identical ρ + values (−1.05 and 1.06), thus suggesting that the coordination between the metal and the radical does not play a significant role in the CAN-promoted oxidative additions

( S )-2-Pyridyl-imino-[2.2]paracyclophane ligands 1 and 2 were synthesized by a condensation reaction of 2-COR-C 5 H 4 N ( 1 : R = H; 2 : R = Me) with enantiopure (−)- S -amino-[2.2]-paracyclophane. The reactions of 1 and 2 with [Ru(η 6 -cymene)Cl(μ-Cl)] 2 afforded complexes [Ru(η 6 -cymene)Cl(N,N)]X ( 3 : N,N = 1 ; 4 : N,N = 2 ; X - = BPh 4 - , PF 6 - , BF 4 - ) that were completely characterized in solution. For 4 PF 6 the solid state structure was determined by X-ray single-crystal diffractometric studies. Two diastereoisomers [( S Ru , S L ) and ( R Ru , S L )] were obtained in solution due to the presence of the planar chirality of paracyclophane (L) and the central chirality on ruthenium. 1 H-NOESY NMR experiments were used to determine the chirality of the metal center and, consequently, to identify ( S Ru , S L ) and ( R Ru , S L ) diastereoisomers. The cymene orientation, obtained by intramolecular 1 H-NOESY NMR investigations, and the relative anion–cation position, determined by interionic 1 H-NOESY or 19 F, 1 H-HOESY NMR studies, depended on the nature of the diastereoisomer.

Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthr-1-yl)- and 2-(phenanthr-2-yl)propionic acids 1-5 were prepared using phenanthren-1(2H)-ones 6a-c as key intermediates. Thus, ethyl 2-(fluorophenanthryl)propionates 11 were obtained in good yields by Reformatsky reaction of 6a-c with ethyl 2-bromopropionate followed by dehydratation and DDQ-promoted aromatization of the resulting beta-hydroxyesters. Side-chain alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 14 were obtained by bromine/lithium permutation of dihydrophenanthryl bromides 12a-c with butyllithium followed by quenching of the lithiated intermediates with methyl pyruvate or ethyl 3,3,3-trifluoropyruvate and subsequent DDQ-promoted aromatization. The alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 25 were prepared by reacting 8-bromo-1,3-difluorophenanthrene 24 with butyllithium for 10 seconds at -110 degrees C and subsequent addition of the suitable pyruvate to the lithiated intermediates. Alkyl 2-hydroxy-2-(phenanthr-2-yl)propionates 26 and 29 were suitably obtained by site-selective metalation of 1,3-difluorophenanthrene 28 and the bromophenanthrene 24, respectively, with LDA followed by quenching of the metalated intermediates with the suitable alkyl pyruvate. Fluorination of the above alpha-hydroxypropionates with DAST, followed by the alkaline hydrolysis, allowed the expected 2-(phenanthryl)propionic acids 1-5 to be obtained in satisfactory overall yields.

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.

Rates of E2 elimination of D,L-1,2dichloro-1,2-diphenylethane (1) and the analogous dibromide (2) were measured in aqueous cetyltrimethylammonium chloride and hydroxide (CTACI and CTAOH), cetyltripropylammonium hydroxide (CTPAOH), didodecyldimethylammonium chloride and hydroxide (DDDACI and DDDAOH), and N,N-dimethyl-N-(2-hydroxyethyl)-n-hexadecylammonium hydroxide (DOH,OH). Micelles or other association colloids of these surfactants increase rates in solutions that contain OH-, and DOH,-OH is much more effective than the nonfunctional surfactants. Variations of first-order rate constants, k obs , with [surfactant] or [OH-] are fitted by a pseudophase model with water and micelles as distinct reaction media, to give second-order rate constants in the latter. These rate constants are in the sequence DOH,OH > CTPAOH DDDACl > DDDAOH CTAOH > CTACl. Micelles favor reactions of 2 over 1, relative to reactivities in water, due to differences in amphiphilic interactions with the leaving halide ions.

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 use of dielec. measurements to assign mol. configurations was examd. with model compds. of the chloroalkane, chloroalkene and chlorocumulene type. A dielec. microcell is described which allowed measurements of 0.35 mL samples under exclusion of air. Both benzene and cyclohexane were used as solvents. Different theories of dielec. const. are compared to evaluate dipole moments. Dipole moments are analyzed in terms of bond moments. The results can be summarized as follows: (i) dielec. measurements are feasible up to 1 M solns. without substantial deviation from linearity; (ii) in general, the dipole moments found in both solvents are similar; the arom. solvent, however, causes a substantial decrease of the values obtained for chloroalkenes with two bulky substituents at the double bonds; (iii) the (E) isomers of chloroalkenes exhibit significantly higher dipole moments than the corresponding (Z) isomers; (iv) isomers of nonchlorinated alkenes of cumulenes with dipole moments below 0.6 D cannot be discriminated dielec.; (v) on the other hand, if the dipole moments of the compds. exceed 1 D, configurations can be assigned unambiguously on the basis of dielec. data even in cases where other approaches fail. [on SciFinder (R)]

CAN promoted oxidative cyclization of dimethyl 4-pentenylmalonate has been investigated in MeOH and in AcOH. The product distribution and the regioselectivity of the reaction (5-exo/6-endo ratio) appear to be very sensitive to the reaction conditions as well as the presence and the nature of copper salts, which can also be exploited from the synthetic point of view.

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.

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

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

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

Elimination from 3α-chloro-3β-methyl-(1) and 3β-chloro-3α-methyl-5α-cholestane (2) to give 3-methylene-5α-cholestane (exo-olefin) and 3-methyl-5α-cholest-2-ene (endo-olefin) has been investigated in ButOK–ButOH solution. The exo:endo olefin ratio is affected by the ButOK concentration but does not depend significantly upon the conformation of the chlorine substituent. This also holds for the reaction rates since the endo-olefin is formed at 100° only 1.7 fold faster from (1)(axial chlorine) than from (2)(equatorial chlorine). In contrast, elimination from 3α-chloro-5α-cholestane (3) is ca. 500 fold faster than from the equatorial isomer (4). The small difference between (1) and (2) in the rate of formation of the endo-olefin is due to compensation between enthalpy and entropy factors. A similar situation is also observed when the exo-olefin forming reactions from (1) and (2) are considered. The kinetic data and the activation parameters support the hypothesis that both olefins are formed from (2) in an anticoplanar process involving a skew-boat conformation.

Etude cinetique et etude des produits de l'elimination a partir des meso-dichloro-1,2 diphenyl-1,2 ethane, erythro-chloro-1 fluoro-2 diphenyl-1,2 ethane et meso-difluoro-1,2 diphenyl-1,2 ethane par t-BuOK dans t-BuOH en presence et en l'absence de 18-crown-6.

3-Acyl- and 3-carboalkoxyfurans can be prepared in 30–55% yield by the oxidative addition of 1,3-dicarbonyl compounds to vinylic acetates induced by eerie ammonium nitrate.

Unsymmetrical 1,4-diketones are prepared in good yields (60–80%) by cerium (IV) ammonium nitrate oxidative cross-coupling between 1,2-disubstituted and 1-substituted trimethylsilyl enol ethers.

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