New concepts for regio- and stereoselective bis- and triscyclopropanations of C60

The synthesis of isomerically multiple adducts of C(60) with a defined three-dimensional structure is still one of the most challenging tasks of exohedral fullerene chemistry. The inherent regioselectivity of successive additions of addends such as malonates to the fullerene's [6,6]-double bonds is only moderate. In most cases difficult-to-isolate mixtures of regioisomers are obtained. The regioselectivity can be significantly improved if multifunctional addends able to undergo two or more additions are allowed to react with C(60). Preorganization and minimization of strain energy within the addend skeleton reduce the number of sterically allowed addition patterns. Improved concepts for highly regio- and stereoselective bis- and triscyclopropanations of C(60) are described. Two examples of the bisadditions with complete regioselectivity leading to trans-2- and cis-2 are presented. Here, the two malonate binding sites are linked by rigid tetraphenylporphyrin and calix-[4]-arene spacers. Selective trisadditions were achieved with the easy-to-synthesize and easy-to-modify tripodal addends 5-7, where the malonates are held together by a focal aryl moiety. Another very elegant approach for bis- and trisadditions involves cyclo-[n]-alkylmalonates. Selection between addition patterns with and without rotational axes is possible by choosing the right combinations of the flexible alkyl chains connecting the malonates. If alkyl chains of identical lengths are used bis- and trisadducts such as 19-21 and 25 with rotational symmetry are formed with high regioselectivity. These addition patterns are avoided if cyclo-[n]-malonates containing alkyl chains of different lengths are employed. In this case adducts such as 26 and 27 with C(s)-symmetry are formed. The use of the chiral cyclo-[3]-malonate 28 allows for the regio- and stereoselective synthesis of the enantiomerically pure e,e,e-trisadducts 29 and 30 containing an inherently chiral addition pattern with C(3)-symmetry.     

Mesomorphic properties of cyanobiphenyl dimers with a central malonate unit

A series of cyanobiphenyl dimers attached via alkoxy spacers to a central malonate were prepared, and the mesomorphic behaviour was studied by differential scanning calorimetry (DSC), polarised optical microscopy and X-ray diffraction (Wide-angle X-ray scattering and Small-angle X-ray scattering). Depending on spacer lengths and substitution of the malonate, nematic and smectic A mesophases with pronounced odd–even effect were observed. C-2-unsubstituted malonates formed nematic phases for chain lengths C₆–C₁₄, while C₁₂ and C₁₄ homologues displayed additional smectic A phases. In contrast, malonates with fluorinated tails at C-2 displayed exclusively smectic A phases. Remarkably, the X-ray diffraction profile of the smectic A phase of the C-2-unsubstituted C₁₂ malonate showed a fundamental (001) and the corresponding third-order (003) diffraction peak, but no (002) reflection. Using Fourier analysis, the diffraction pattern was converted to an electron density profile, which was in good agreement with the proposed packing model of the SmA mesophase based on a horseshow- or hairpin-like conformation of the malonate.     

Tandem three-component reactions of aldehyde, alkyl acrylate, and dialkylmalonate catalyzed by ethyl diphenylphosphine

A new highly efficient three-component reaction of alkyl acrylate, aldehyde and dialkyl malonate using ethyl diphenylphosphine as organocatalyst has been described. Various highly functional compounds bearing hydroxyl groups and the ester functions can be easily prepared in moderate to good yields according to our one-step procedure. The reactions are believed to proceed via Morita-Baylis-Hillman reactions of alkyl acrylate and aldehydes, followed by the Michael addition reactions of dialkyl malonates. Our reactions indicated that the intermediate species formed in the phosphine-catalyzed MBH reaction are an effective organic base to catalyze the Michael addition reactions of dialkyl malonates to the preformed MBH adducts.     

Selective syntheses of novel polyether fullerene multiple adducts

We have applied a modified macrocyclic tether approach to control multiple additions to C60. The technique of 3He NMR was used to confirm the selective formation of specific C60 multiple adducts by the macrocyclic tether approach. An oligoglycol was used as a flexible linker to produce macrocyclic polyether-linked malonates 5, 6, 8, and 9 under solid-liquid PTC (phase-transfer-catalysis) conditions. The formation of a single C60 tris-adduct, 3, from macrocyclic malonate 1 and 3He@C60 was proven by 3He NMR. Similarly, multiple additions to C60 of macrocyclic polyether malonate 5 gave C60 bis-adduct 10 selectively, while the reaction of C60 with macrocyclic malonate 8 gave bis-adducts 11 and 12. A similar process with macrocyclic malonate 6 gave tris-adduct 13 with high selectivity as well. Saponification of these C60 multiple adducts gives the corresponding polyacids that are potentially useful in biological applications. Macrocyclic polyether fullerenes are a new class of ionophores, which could be interesting for molecular recognition and for the development of biosensors.     

Palladium-catalyzed arylation of malonates and cyanoesters using sterically hindered trialkyl- and ferrocenyldialkylphosphine ligands.

Palladium-catalyzed reactions of aryl bromides and chlorides with two common stabilized carbanions-enolates of dialkyl malonates and alkyl cyanoesters-are reported. An exploration of the scope of these reactions was conducted, and the processes were shown to occur in a general fashion. Using P(t-Bu)(3) (1), the pentaphenylferrocenyl ligand (Ph(5)C(5))Fe(C(5)H(4))P(t-Bu)(2) (2), or the adamantyl ligand (1-Ad)P(t-Bu)(2) (3), reactions of electron-poor and electron-rich, sterically hindered and unhindered aryl bromides and chlorides were shown to react with diethyl malonate, di-tert-butyl malonate, diethyl fluoromalonate, ethyl cyanoacetate, and ethyl phenylcyanoacetate. Although alkyl malonates and ethyl alkylcyanoacetates did not react with aryl halides using these catalysts, the same products were formed conveniently in one pot from diethylmalonate by cross-coupling of an aryl halide in the presence of excess base and subsequent alkylation.     

Non-template synthesis of ‘N4’ di- and tetra-amide macrocylic ligands with variable ring sizes

Nine new macrocyclic ligands containing two- or four-amide groups have been prepared by the cyclization reaction of three different diamines with acid chlorides (oxalyl dichloride or malonyl dichloride), diesters (diethyl oxalate or diethyl malonate) or 1,2-dichloroethane. The macrocycles prepared are four tetraaza-14-crown-4, four tetraaza-15-crown-4 and one tetraaza-16-crown-4. All the macrocyclic ligands were characterized by elemental analysis and, IR, UV, NMR and mass spectral investigations.     

Liquid crystalline compounds having a tribranched structure: substituted malonic esters consisting of two Schiff's base units and a cholesteryloxyalkyl substituent

New tribranched thermotropic liquid crystal compounds were synthesized and their liquid crystalline properties studied by differential scanning calorimetry, X-ray diffraction and polarizing optical microscopy. The compounds are the bis-{10-[4-(4-alkylphenyliminomethynyl)phenoxy]decyl} 2-[6-(cholesteryloxy)hexyl]malonates and the corresponding alkoxy derivatives. These compounds contain three mesogenic units, two identical Schiff's base type mesogens and one cholesteryl either moiety, interconnected in a tribranched structure via spacers. The cholesterly moiety is attached to the malonic acid core through an oxyhexamethylene spacer while the two Schiff's-base moieties are attached through oxydecamethylene spacers. The terminal alkyl group of the Schiff's base unit is either a butyl or decyl group, and the alkoxy terminal group is either a butoxy or decyloxy chain. All the compounds form only an enantiotropic smectic phase, most probably of the smectic C type. The larger spacings determined by small angle X-ray diffraction range from 3.3 to 4.1 nm, which are much shorter than the end-to-end distance (5.9-7.4 nm) of the molecules estimated using molecular models assuming an all trans extended conformation for all the alkyl spacers.     

New 2+2, 3+3 and 4+4 macrocycles derived from 1,2-diaminocyclohexane and 2,6-diformylpyridine

Two new Schiff base macrocycles - a 4+4 condensation product and a meso-type 2+2 condensation product - were obtained in a reaction of trans-1,2-diaminocyclohexane and 2,6-diformylpyridine. Reduction of these compounds led to the corresponding 4+4 and 2+2 macrocyclic amines. The macrocycles were characterised by NMR spectroscopy and electrospray mass spectrometry. The symmetry and stereochemistry of these macrocycles, as well as of new 3+3 and 4+4 diastereomers identified in solution, has been established. X-Ray structures of the 2+2 and 4+4 Schiff base macrocycles confirm the configurations determined on the basis of spectroscopic investigations. The crystal structures reveal that the centres of the square-shaped 4+4 macrocycles form channels as a result of columnar stacking.     

Reactions of Zinc Enolates Formed from 1-Aryl-2-bromo-2-phenylethanone or 2-Bromoindanone and Zinc,with Dimethyl 2-(1-Arylmethylene)malonates

Zinc enolates formed from 1-aryl-2-bromo-2-phenylethanones and zinc react with dimethyl 2-(1-arylmethylene)malonates to afford dimethyl 2-(1,3-diaryl-3-oxo-2-phenylpropyl)malonates. The latter react with cyclohexylamine, piperidine, or morpholine to give the corresponding monosubstituted amides. The zinc enolate derived from 2-bromoindanone and zinc reacts with dimethyl 2-(4-bromobenzylidene)malonate, yielding dimethyl 2-[(4-bromophenyl)(1-oxoindan-2-yl)methyl]malonate. The final products largely form as a single diastereomer.     

Topologically novel multiple rotaxanes and catenanes based on tetraurea calix[4]arenes

Calix[4]arenes bearing at their wide rim four urea residues easily form hydrogen bonded dimeric capsules. This has been used to preorganise alkenyl functions attached to these urea groups for their controlled connection via metathesis reaction. Multimacrocyclic tetraurea derivatives are thus obtained in excellent yields via heterodimers which are formed exclusively with tetratosylurea derivatives. Heterodimerisation of such bis- and tetraloop tetraureas leads analogously to multicatenanes, or to rotaxanes by stoppering. Huge macrocycles are detached from tetraloop derivatives by cleavage of the urea function.     

Synthesis of nitrogen and sulfur macrocycles with cis exogenous oxygen and sulfur donor atoms

A series of new N4 and N8 macrocycles has been prepared, that includes cis-exogenous O2, S2 and S/O atoms to allow chelation to a metal external to the macrocyclic ring. We found that thioamide units within the macrocycles were unstable to attack by secondary amines and thus alkylated precursors containing only tertiary amines could lead to exogenous-S2 macrocycles. Cyclisation of alkylated tetraamine precursors with dimethyloxalate or dithiooxamide led to both N4 and N8 macrocycles via 1 + 1 and 2 + 2 cyclisation reactions with exogenous-O2 or S2 respectively. Alkylation of preformed exogenous-O2 macrocycles was explored and led to alkyl substitution at the secondary amine nitrogens in the ring, however synthesis of these species was overall lower yielding than cyclisation using alkylated tetraamine precursors. Thionation of an exo-O2 macrocycle using an analogue of Lawesson's Reagent led to formation of the analogous exogenous-S2 and exogenous-O,S macrocycles. Related S2N2 macrocycles with exogenous-O2 were prepared by a cyclisation route but could not be isolated free of larger ring analogues.     

Enantioselective palladium-catalyzed addition of malonates to 3,3-difluoropropenes

Monofluoroalkenes bearing a malonate unit at the β position can be synthesized by the enantioselective addition of diesters to 3,3-difluoropropenes. The difference in reactivity regarding the geometry and the substituents of the alkene of the 3,3-difluoropropenes, as well as the alkyl groups of the malonates, was studied and limitations were identified. The reaction was also performed with different 3,3-difluoropropenes. Further synthetic transformations of a newly functionalized monofluoroalkene were also accomplished.     

Polybromoaromatic Compounds: IX. Reactions of Polybromobenzyl Bromides with Enolates Derived from Some Dicarbonyl Compounds

The reaction of polybromobenzyl bromides RC₆Br₄CH₂Br (R = Br, OCH₃) with diethyl malonate sodium salt in ethanol and dimethylformamide leads to formation of diethyl 2-(polybromobenzyl)malonates, whereas in aqueous ethanol ethyl polybromobenzyl malonates are formed. The same polybromobenzyl bromides react with an equimolar amount of ethyl acetoacetate sodium salt or acetylacetone sodium salt to give C-alkylation products; with excess sodium enolates ethyl 3-(polybromophenyl)propionates and 4-(polybromophenyl)-2-butanones are formed, respectively.     

Synthesis and thermal behaviour of liquid crystalline pyridinium bromides containing a biphenyl core

A range of new pyridinium bromides was synthesized by the quaternization of different substituted pyridines with a group containing a biphenyl core and alkyl chains of differing lengths. The phase behaviour of the pyridinium bromides was studied by differential scanning calorimetry, polarizing optical microscopy and powder X-ray diffraction. It is shown that pyridinium moieties, linked to a rod-like biphenyl core via an alkyl spacer, can form ionic liquid crystals. Unsubstituted pyridinium groups promote mesomorphism. Liquid crystalline phases are formed only from 2- and 4-ethyl substituted pyridinium groups with sufficiently long alkyl terminal chains and spacers; i.e. decyl chains on both sides of the biphenyl core. Both the substitution pattern at the pyridinium group and the alkyl chain length have an influence on the polymorphism of the smectic phases. 3,5-Dimethyl substitution hinders mesophase formation.     

Synthesis and thermal behaviour of liquid crystalline pyridinium bromides containing a biphenyl core

A range of new pyridinium bromides was synthesized by the quaternization of different substituted pyridines with a group containing a biphenyl core and alkyl chains of differing lengths. The phase behaviour of the pyridinium bromides was studied by differential scanning calorimetry, polarizing optical microscopy and powder X-ray diffraction. It is shown that pyridinium moieties, linked to a rod-like biphenyl core via an alkyl spacer, can form ionic liquid crystals. Unsubstituted pyridinium groups promote mesomorphism. Liquid crystalline phases are formed only from 2- and 4-ethyl substituted pyridinium groups with sufficiently long alkyl terminal chains and spacers; i.e. decyl chains on both sides of the biphenyl core. Both the substitution pattern at the pyridinium group and the alkyl chain length have an influence on the polymorphism of the smectic phases. 3,5-Dimethyl substitution hinders mesophase formation.     

Self-assembly of novel macrocyclic aminomethylphosphines with hydrophobic intramolecular cavities

Novel macroheterocyclic tetraphosphines, namely, 1,1',5,5'-bis(arylene)-bis(1,5-diaza-3,7-diphosphacyclooctanes) 2-6, were obtained without the use of high-dilution techniques or any matrix by the reaction of bis(hydroxymethyl)organylphosphines with primary aromatic diamines containing two p-phenylene fragments linked by various one-atom bridges in a molecular self-assembly process. The structures of 4, 5 and 6 were investigated by X-ray crystal structure analyses. The macrocyclic cavities can be described as a truncated rhombohedral prism with side faces formed by phenylene rings and 1,5-diaza-3,7-diphosphacyclooctanes in the truncated acute angles. In the crystals of these macrocycles, solvating DMF molecules are present, and a methyl group from each of two DMF molecules penetrates the macrocyclic cavities of 4 and 5 from either side, whereas only one disordered molecule of DMF penetrates the cavity of macrocycle 6. Different types of crystal packing are observed for the P-benzyl-substituted compounds 4 and 5 and for the P-mesityl-substituted compound 6: for 4 and 5 the formation of alternating layers containing the macrocycles and the DMF molecules is observed, in which the cavities of the macrocyclic molecules form channels and the DMF molecules are located in the centers of the channels; in the crystal of 6, six molecules are arranged around the 3 axis in the fashion of a six-bladed propeller.     

A general organocatalytic enantioselective malonate addition to alpha,beta-unsaturated enones

A general enantioselective organocatalytic conjugate addition procedure of a variety of malonates to alpha,beta-unsaturated enone systems is presented. The reaction is efficiently catalysed by the pyrrolidinyl tetrazole catalyst 1. Cyclic, acyclic and aromatic enones can be used and the reaction with ethyl malonates 3 b provides the Michael addition products in high yields with good to excellent enantioselectivities. Since only 1.5 equivalents of malonate are used as a reagent, the reaction is readily scaled and practical to operate. Furthermore, the malonate addition products can be easily mono decarboxylated without loss in enantiomeric excess by enzymatic or sodium hydroxide mediated methods.     

The lowest-energy ligand to metal charge-transfer absorption band of trans-[OsO2(malonate)2]2-

The resolved structure of the lowest-energy oxo to osmium charge-transfer absorption band of trans-[OsO2(malonate)2]2- is analyzed on the basis of the exact molecular Ci symmetry determined from the structure of a crystal used for spectroscopy. The multiple progressions observed in the polarized spectra are rationalized in terms of the deviations from idealized D4h point group symmetry and compared to the spectra observed for complexes with D2h symmetry such as trans-[OsO2(oxalate)2]2- that show only a single dominant progression for this transition.     

Gels of hydrophobically modified ethyl(hydroxyethyl) cellulose cross-linked by amylose: effects of hydrophobe architecture

Previous work has shown that amylose (AM) can cross-link hydrophobically modified polymers by inclusion complexation, whereby thermoreversible cold-setting gels are formed. Here we investigate the complexation of AM with different samples of hydrophobically modified ethyl(hydroxyethyl) cellulose (HMEHEC), distinguished by differences in the architecture of the hydrophobes (the hydrophobic side chains). All hydrophobes, except one, were based on linear alkyl chains, but with varying chain lengths (C12-C14). In addition, some samples contained short hydrophilic "spacers", consisting of 2-5 ethylene oxide units, between the alkyl chains and the EHEC backbone. Gels of varying strength were obtained for the different AM/HMEHEC samples. The alkyl chain length seemed to be the major factor affecting the gel strength, with longer alkyl chains giving stronger gels. For similar alkyl chain lengths, stronger gels were obtained when a spacer was present. Addition of AM caused a small increase of the cloud points of HMEHECs with C14 hydrophobes in water. Time-dependent effects and effects of the sample preparation procedure were also investigated. The reversibility of the gelation with respect to shear was confirmed. A gel destroyed by added surfactant was shown to reform on removal of the surfactant by dialysis.     

Engineering solid-state morphologies in carbazole-ethynylene macrocycles

We present a crystallographic study that systematically investigates the effects of the n-alkyl side-chain length on the crystal packing in shape-persistent macrocycles. The solid-state packing of carbazole-ethynylene-containing macrocycles is sensitive to the alkyl-chain length. In macrocycles containing n-alkyl side chains up to nine carbons in length, face-on aromatic π interactions predominate, while the addition of one carbon leads to a completely different packing arrangement. Macrocycles with C(10) or C(11) chains exhibit a novel packing motif wherein the alkyl chains intercalate between macrocycles, leading in one case to continuous solvent-filled channels. When crystals of the C(10) macrocycle are bathed in solvent, the included molecules exchange with the external solvent, and the alkyl chain disorder changes in response to changes in the guest volume in order to retain crystallinity. Powder X-ray diffraction data indicate that alkyl-macrocycle interactions in the longer chains "emulate" the distances typical of face-to-face π interactions, leading to deceptive indicators of π stacking.