Contractive Annulation: A Strategy for the Synthesis of Small,Strained Cyclophanes and Its Application in the Synthesis of [2](6,1)Naphthaleno[1]paracyclophane

A new synthetic strategy (contractive annulation) for the synthesis of highly strained cyclophanes has been conceived and its viability has been demonstrated through a nine‐step synthesis of [2](6,1)naphthaleno[1]paracyclophane from [2.2]paracyclophane.     

Synthesis of perfluoro[2.2]paracyclophane

A synthesis of perfluoro[2.2]paracyclophane has been sought ever since the partially fluorinated octafluoro[2.2]paracyclophane (AF4) was prepared and its chemistry studied. This compound has now been prepared in 39% yield from the precursor, 1,4-bis(chlorodifluoromethyl)-2,3,5,6-tetrafluorobenzene by its reaction with Zn when heated in acetonitrile at 100 degrees C. Two preparations of the precursor, first from 1,4-dicyano-2,3,5,6-tetrachlorobenzene and an improved method beginning from 1,2,4,5-tetrachlorobenzene, are also described as are key comparisons to our related synthesis of AF4.     

Synthesis of novel planar-chiral [2.2]paracyclophane derivatives as potential ligands for asymmetric catalysis

The synthesis of a variety of new 4,5-disubstituted [2.2]paracyclophane derivatives has been achieved employing different cross-coupling reactions. By this methodology, a heteroatom-variation of successful catalyst ligands was achieved, giving rise to a modular ligand system. The X-ray structure of 4-hydroxy-5-(1′-hydroxy-1′-phenylethyl)-[2.2]paracyclophane was determined to elucidate the configuration. Additionally, a diastereoselective synthesis of planar- and central-chiral 4-([2.2]paracyclophanyl)ethylamine was achieved, thus resulting in a planar- and central-chiral phenyl ethylamine analogue.     

Synthesis of [2.2]paracyclophane-pseudo-ortho-dicarboxylic acid

An efficient three-step synthesis of [2.2]paracyclophane-pseudo-ortho-dicarboxylic acid by dibromination of [2.2]paracyclophane, thermal isomerization of the resultingpseudopara-dibromide topseudo-ortho-isomer, followed by lithiation/carboxylation was developed. The possibility of preparation of two other novelpseudo-ortho-disubstituted carbonyl derivatives, 4-carboxy-12-(1-oxopenthyl)-[2.2]paracyclophane and di(4-carboxy[2.2]paracyclophanyl-12)ketone, was demonstrated when an excess of lithiation reagent (4 or 10 eq.) was used in the final step. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2001–2004, November, 1997.     

Synthesis ofo-andm-carborane derivatives of [2,2]paracyclophane and abnormal Clemmensen reduction of ketones of the [2,2]paracyclophane and carborane series

Methods for the synthesis of [2,2]paracyclophane derivatives containingo- andm-carboranyl substituents in position 4, separated from the [2,2]paracyclophane system by one or two C atoms (alcohols and ketones) were developed. The Clemmensen reduction of a number of ketones of the [2,2]paracyclophane ando-carbonane series occurs abnormally. The reduction of 1-benzoyl-o-carboranes to the corresponding alcohols by zinc in ethanol in a neutral medium was performed for the first time. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1206–1211, June, 1997.     

The first synthesis and characterization of both diastereomers of a di[2.2]paracyclophane: 4,4'-bis(1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane)

The synthesis and characterization of both diastereomers of a system comprised of two [2.2]paracyclophane units linked through a single 4,4' bond are described. Both the meso and d,l diastereomers of 4,4'-bis(octafluoro[2.2]paracyclophane) have been prepared via a palladium-catalyzed reductive homocoupling reaction by copper, producing a 3:2 ratio of meso and d,l diastereomers. A similar reductive homocoupling of pseudo-o-iodotrifluoromethyloctafluoro[2.2]paracyclophane gave only the analogous meso diastereomer. Single-crystal X-ray structures were obtained for all of the diparacyclophane products.     

Phane properties of [2.2]paracyclophane/dehydrobenzoannulene hybrids

A series of [2.2]paracyclophane/dehydrobenzo[14]annulene (PC/DBA) hybrids (hydrocarbons 5, 6, 9, 10 b, and 10 c), [2.2]paracyclophane/dehydro[14]annulene (PC/DA) hybrids (7 and 8) and suitable model systems (11, 12, and 33) has been synthesized. Comparison of the electronic absorption spectra in each series of compounds provides further insight into the global communication between the decks in the [2.2]paracyclophane unit.     

Photochemical synthesis of [2.2](3,8)-pyridazinophane and quinolinophane-2(1H)-one as well as synthesis of [2](5,8)-quinolinophanes and fused spiro-pyranoindanoparacyclophanes

Syntheses of various classes of unreported heterophanes derived from [2.2]paracyclophane are herein reported. The key to their successful synthesis depends on the photochemical synthesis of pyridazinophane and quinolinophane-2(1H)-one from freshly prepared 4-([2.2]paracyclophanyl)-azo-4′-[2.2]paracyclophane and 4-([2.2]paracyclophanyl)cinnnamanilide, respectively. Reactions of 4-amino-[2.2]paracyclophane with either acetyl- or benzoylacetone afforded condensed products. Then ring closure using polyphosphoric acid (PPA) at 120°C gave, in near quantitative yields, quinolinophanes. Reactions of [2](4,7)-indano-[2]paracyclophane-1-ylidene-propanedinitrile with active methylene compounds afforded fused spiro-pyranoindanoparacyclophane derivatives.     

The synthesis and directed ortho-lithiation of 4-tert-butylsulfinyl[2.2]paracyclophane

The ortho-lithiation of one diastereoisomer of 4-tert-butylsulfinyl[2.2]paracyclophane is the key step to the synthesis of a range of 4,5-disubstituted [2.2]paracyclophane derivatives.     

Synthesis of N-methyl-3-aza[10] paracyclophane: A rigid analog of phenethylamine

The synthesis of N-methyl-3-aza[10]paracyclophane is reported which represents the first example of this ring system being formed via an acyloin reaction. This 3-aza[10]paraeyclophane ring system behaves physiochemically inbetween the normal [9]- and [10]paracyclophane ring systems. Reductive desulfurization of N-methyl-3-aza[10]paracyclophane-6-ethylene thioketal in ethanol provides a small amount of the title compound and an unexpected, ring-opened product, N-ethyl-N-methyl-p-heptylphenethylamine. A possible mechanism for the ring-opening process is suggested.     

Synthesis of [2.2]Paracyclophane-Based Glycidic Amides Using Chiral Ammonium Ylides

An ammonium ylide-mediated stereoselective protocol for the synthesis of a series of novel [2.2]paracyclophane-based epoxides starting from racemic 4-formyl[2.2]paracyclophane has been developed. By using achiral ammonium salts as ylide precursors, the corresponding epoxide products were obtained in isolated yields up to 76 % and with diastereoselectivities up to d.r.=9 : 1. When carrying out the reaction with chiral ammonium salts instead, the products were accessible with e.r.>93.5 : 6.5 and d.r.>3 : 1, accompanied with a moderately enantioselective kinetic resolution of the racemic starting aldehyde (e.r.=75 : 25).     

Synthesis, characterization, and spectroscopy of 4,7,12,15-[2.2]paracyclophane containing donor and acceptor groups: impact of substitution patterns on through-space charge transfer

This paper reports the synthesis of 4,7,12,15-tetra(4'-dihexylaminostyryl)[2.2]paracyclophane (1), 4-(4'-dihexylaminostyryl)-7,12,15-tri(4' '-nitrostyryl)[2.2]paracyclophane (2), 4,7-bis(4'-dihexylaminostyryl)-12,15-bis(4' '-nitrostyryl)-[2.2]paracyclophane (3), 4,7,12-tris(4'-dihexylaminostyryl)-15-(4' '-nitrostyryl)[2.2]paracyclophane (4), 4,15-bis(4'-dihexylaminostyryl)-7,12-bis(4' '-nitrostyryl)[2.2]paracyclophane (5), and 4,12-bis(4'-dihexylaminostyryl)-7,15-bis(4' '-nitrostyryl)[2.2]paracyclophane (6). These molecules represent different combinations of bringing together distyrylbenzene chromophores containing donor and acceptor groups across a [2.2]paracyclophane (pCp) bridge. X-ray diffraction studies show that the lattice arrangements of 1 and 3 are considerably different from those of the parent chromophores 1,4-bis(4'dihexylaminostyryl)benzene (DD) and 1,4-di(4'-nitrostyryl)benzene (AA). Differences are brought about by the constraint by the pCp bridge and by virtue of chirality in the "paired" species. The absorption and emission spectra of 1-6 are also presented. Clear evidence of delocalization across the pCp structure is observed. Further, in the case of 2, 3, and 4, emission from the second excited state takes place.     

Preparation of planar chiral amino phenols based on the [2.2]paracyclophane backbone

The synthesis of various planar and central chiral secondary and tertiary amino phenols based on the [2.2]paracyclophane backbone is described. Planar chiral tertiary amino phenols are prepared by reductive amination of 5-formyl-4-hydroxy[2.2]paracyclophane (FHPC) with secondary amines. The reduction of imine and ketimine precursors, as well as the 1,2-addition to these compounds is also described.     

Synthesis of planar chiral [2.2]paracyclophane Schiff bases for the enantioselective Henry reaction

A series of diastereomerically pure Schiff base ligands based on [2.2]paracyclophane backbones were synthesized and separated. The new planar chiral [2.2]paracyclophane Schiff bases were used as ligands in Cu-catalyzed asymmetric Henry reactions with high yields and enantioselectivities.     

Synthesis of novel mono- and diaryl-substituted [2.2]paracyclophanes

The cross-coupling reactions of 4-bromo[2.2]paracyclophane withp-tolylmagnesium bromide in the presence of various palladium and nickel complexes have been studied. It was found that [1,1 -bis(diphenylphosphinoferrocene)]palladium dichloride (PdCl₂ · dppf) shows the highest catalitic activity in this reaction. A series of new mono- and diaryl [2.2]paracyclophane derivatives with various substituents in the arene ring have been synthesized using this catalyst. It was shown that it is possible to cross-couple organozinc [2.2]paracyclophane derivatives with aromatic bromides. The composition and structure of the compounds obtained have been established on the basis of elemental analysis and spectral data. Some correlations between the structure and spectral parameters of mono- and diarylsubstituted [2.2]paracyclophanes have been found.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1081–1085, June, 1994.The present work was financially supported by the Russian Foundation for Basic Research (Project No. 93-03-5246).The authors wish to express their gratitude to Prof. N. A. Bumagin for his scientific interest and helpful discussions.     

The first three aromatic tribromides of the [2.2]paracyclophane series

From the reaction mixtures in the uncatalyzed polybromination of [2.2]paracyclophane by the action of excess Br₂ in CCl₄, there have been found along with the known products — 4,15- and 4,16-dibromo[2.2]paracyclophanes — two new aromatic tribromides of this series, which have been isolated in pure form: 4,12,15- and 4,15,16-tribromo[2.2]paracyclophanes. Special experiments demonstrated that the mixtures of these tribromides are formed as a result of competitive monobromination of 4,15-dibromo[2.2]paracyclophane; the 4,15,16-tribromo[2.2]paracyclophane, together with still another newly isolated isomer of this series — 4,8,12-tribromo[2.2]paracyclophane — is formed as a result of competitive monobromination of 4,16-dibromo[2.2]paracyclophane. As an explanation of the features of the orienting effect of substituents in these competing reactions, a rule was proposed: On the conventional orientation (from the electronic point of view) of entry of the bromine atom into the substituted ring (para > ortho > meta), a steric limitation is imposed on its attack in the pseudo-gem-position, owing to the bulky bromine atom that is transannularly positioned above it in the neighboring aromatic ring. The structures of all of the tribromides were established on the basis of elemental analyses, mass spectrometry, and¹H NMR spectrometry (including PMR using the homonuclear Overhauser effect). The data obtained in this work indicate that the 4,12,15-tribromo[2.2]paracyclophane and 4,15,16-tribromo[2.2]paracyclophane are predecessors of the two tetrabromides previously obtained by Cram — 4,7,12,15- and 4,5,15,16-tetrabromo[2.2]paracyclophanes; and the 4,8,12-tribromo[2.2]paracyclophane is a possible predecessor of 4,8,12,16-tetrabromo[2.2]paracyclophane, which is unknown up to the present time.A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1837–1843, August, 1992.     

Suzuki aryl cross-coupling chemistry using derivatives of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane

An exploration into the scope of Suzuki aryl cross-coupling chemistry using derivatives of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane is reported. The coupling of 4-iodo-1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane with various aryl boronic acids and boronic acid pinacol esters was successful, with the exception of very sterically demanding systems, such as mesityl. The synthesis of the previously unreported 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophanyl-4-boronic acid is described, together with various Suzuki aryl cross-coupling reactions of this new system. Using standard Suzuki methodology, it was possible to prepare dicyclophanes bearing two octafluoro[2.2]paracyclophane units separated by both one and two benzene rings.     

Synthesis of new planar chiral [2.2]paracyclophane Schiff base ligands and their application in the asymmetric Henry reaction

A series of new planar and central chiral ligands based on [2.2]paracyclophane backbones were designed and prepared from enantiomerically pure 4-amino-13-bromo[2.2]paracyclophane and commercially available chiral amino alcohols. Their application in a copper-catalyzed asymmetric Henry reaction resulted in secondary alcohols with high yield and excellent selectivity for active aldehydes (up to 94% ee). This is a successful example of employing planar chiral [2.2]paracyclophane ligands in copper-catalyzed reaction.     

14][14]Metaparacyclophane: first example of an [m][n]metaparacyclophane

The synthesis of [14][14]metaparacyclophane, the first [m][n]metaparacyclophane ever known, is described. The reaction sequence began with the bis-chloromethylation of [14]paracyclophane in refluxing CS(2), which yielded a nonseparable mixture of 16,19- and 16,20-bis(chloromethyl)[14]paracyclophane in an 8:1 ratio. Acetolysis of these dichlorides gave the corresponding diacetate mixture from which the minor component 16,20-bis(acetoxymethyl)[14]paracyclophane was isolated and elaborated into the desired cyclophane via the disulfone of 2,15-dithia[16][14]metaparacyclophane and subsequent sulfur dioxide extrusion by a one-flask Ramberg-B?cklund reaction procedure followed by hydrogenation.     

Synthesis of [4.2]cyclophanes

Vinyl $\text{p}$-xylylene cross-dimerizes with other xylylene-type intermediates to yield cycloadducts of the [8+6] and [6+6] type. This reaction provides a simple entry to the [4.2]paracyclophane system as well as the analogous [4.2]cyclophanes containing furan and pyrrole moieties.