Conformations of 10-membered rings in bicyclogermacrene and isobicyclogermacrene

The configurations of the endocyclic double bonds and the conformations of 10-membered rings in bicyclogermacrene (1) and isobicyclogermacrene (3), sesquiterpenes containing a fused 1,1′- dimethylcyclopropane ring, have been elucidated in solution by the use of intramolecular nuclear Overhauser effects. Compounds 1 and 3 adopt conformations A and C, respectively; the double bonds of the former have trans,trans-orientation, and those of the latter trans,cis-orientation.     

Aromaticity and antiaromaticity in 4-, 6-, 8-, and 10-membered conjugated hydrocarbon rings

Recently, we presented a molecular orbital (MO) model of aromaticity that explains, in terms of simple orbital-overlap arguments, why benzene (C(6)H(6)) has a regular structure with delocalized double bonds whereas the geometry of 1,3-cyclobutadiene (C(4)H(4)) is distorted with localized double bonds. Here, we show that the same model and the same type of orbital-overlap arguments also account for the irregular and regular structures of 1,3,5,7-cyclooctatetraene (C(8)H(8)) and 1,3,5,7,9-cyclodecapentaene (C(10)H(10)), respectively. Our MO model is based on accurate Kohn-Sham DFT analyses of the bonding in C(4)H(4), C(6)H(6), C(8)H(8), and C(10)H(10) and how the bonding mechanism is affected if these molecules undergo geometrical deformations between regular, delocalized ring structures and distorted ones with localized double bonds. The propensity of the pi electrons is always to localize the double bonds, against the delocalizing force of the sigma electrons. Importantly, we show that the pi electrons nevertheless determine the localization (in C(4)H(4) and C(8)H(8)) or delocalization (in C(6)H(6) and C(10)H(10)) of the double bonds.     

5,10:13,14-Disecosteroids: novel modified steroids containing 10- and 9-membered rings

In this paper a synthetic pathway to the modified 5,10:13,14-bisfragmentation cholestane derivatives 8-14 is described. The synthesis involves introduction of the 5α- and 14α-hydroxyl groups in the cholestane molecule and subsequent cleavage of the C(5)-C(10) bond in 5α,14α-dihydroxycholestan-3β-yl acetate (4) with the HgO/I₂ reagent and the C(13)-C(14) bond in the stereoisomeric 14α-hydroxy-5,10-secosteroids 5 and 6 with the Pb(OAc)₄/I₂ reagent. Complete and unambiguous ¹H and ¹³C NMR resonance assignments of the obtained secosteroids, as well as the solution conformations of their 10- and 9-membered rings were determined by extensive analysis of 1D and 2D NMR spectral data. The structures and the solid-state conformations of 5,10-secosteroids 5-7 were confirmed by X-ray analysis. All diseco-compounds have a novel 5,10:13,14-disecocholestane skeleton.     

Applications of charge-directed conjugate addition reactions to the formation of 5- and 6-membered rings

Ring constructions through intramolecular trapping of anions generated in charge-directed addition reactions are reported. Intramolecular reactions of internal nucleophiles including Grignard reagents are also described.     

Synthesis of 10-membered and larger rings via free radical methods

The purpose of this review is to discuss 1) how free radical chemistry has contributed to development of new methodologies for the construction of 10-membered and larger macrocycles over the past 32 years; 2) the most well-developed free radical methods for constructing 10-membered and larger rings; and 3) how these methodologies have contributed to solving certain key steps in the synthesis of natural products.     

NMR study of complex formation between TiCl4 and N-Methylated lactams with 7- and 9-membered rings

By analysis of ¹H- and ¹³C-NMR spectra it has been found that in 1,1,2,2-tetrachloroethane-d₂ and CDCl₃ solutions, the lactams (L) 1-methyl-1-azacycloheptca-2-one and 1-methyl-1-azacyclonona-2-one form with TiCl₄ (M) at mole ratios [L]: [M] > 2 two types of complexes of composition ML₂, which differ in the geometrical arrangement of the ligands. The thermodynamic parameters of the exchange of lactams between the two complexes and the uncomplexed state were determined from the temperature dependence of ¹H-NMR line shapes and found to be independent of the lactam ring size.     

Study of the possibility of forming 7- and 9-membered rings in the D-mannitol tricyclic triethyl triphosphite molecule

Conclusions The transesterification reaction was used to synthesize some cyclic phosphites from the 1,34,6-di- and 2,5-O-methylene-D-mannitols and 1,6-dichloro-D-mannitol. 1,4-Butylene glycol and 2,3,4,5-di-O-methylene-D-mannitol do not form cyclic phosphites under the transesterification conditions.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1395–1399, June, 1972.     

7- and 8-membered ring sugars and related systems : 7-Membered rings from diolefins derived from dioxepans via double michael condensations

The possibilities of cyclisation to 7-membered ring sugars containing nitro- and cyano-functions via double Michael condensations of diolefins derived from sugar dioxepans was investigated. With nitromethane cyclised products were obtained while with the larger ethyl cyanoacetate and malononitrile only one double bond was attacked without cyclisation. Treatment of the diolefins with excess ammonia resulted in cyclisation to novel heterocyclic systems containing oxygen and nitrogen often of known stereochemistry; with butylamine no cyclisation occurred. Treatment with hydrogen sulphide also resulted in cyclisation to novel heterocyclic systems containing sulphur and oxygen often of known stereochemistry. In these systems cyclisation only occurs with the smaller reagents.     

Directed diversity-oriented synthesis. Ring-fused 5- to 10-membered rings from a common peptidomimetic 2-pyridone precursor

A variety of ring-fused 2-pyridone-based central fragments were prepared using a strategy inspired by diversity-oriented synthesis. The produced compounds are diverse, yet focused, analogs of biologically active peptidomimetic 2-pyridones.     

Ab inttio structural analysis of some saturated 3- and 4-membered rings

Complete geometry optimizations of the ground states of ten 3- and 4-membered ring compounds have been carried out by ab initio SCF calculations using the gradient method at the 4–21 level. For sulfur, an optimized 3-3-21 basis has been constructed, and the importance of including d-functions is demonstrated. The main purpose of the study was to determine local orientations and geometries of the molecular CH₂-groups, information that is very difficult to obtain from experiment. A simple interaction model seems to account for the CH₂-group distortions in the 3-membered rings considered here, and also for similar structural deformations previously reported in a series of cyclopropyl derivatives.     

Synthesis of cyclic proline-containing peptides via ring-closing metathesis

[reaction: see text] Several dienes embedded in di- and tripeptides which incorporate proline have been prepared and subjected to ring-closing metathesis. Bicyclic peptides of well-defined amide geometry and of varying ring sizes were prepared. Several limitations of the cyclization step were revealed.     

The intramolecular beta-fluorine...ammonium interaction in 4- and 8-membered rings

The structures of 3-fluoroazetidinium hydrochloride and 3-fluoro-1,5-diazacyclooctane hydrobromide are explored both by X-ray diffraction analysis and DFT calculations, and the conformations of these molecules are shown to be significantly influenced by the through space C-F...N+ interaction.     

Supramolecular formation of large hydrogen-bonded rings in the structures of two amino acid derivatives

Two new amino acid derivatives N-(2-oxopyrrolidin-1-ylmethyl)-l-valine (PMV) and N,N-bis(2-oxopyrrolidin-1-ylmethyl)-β-alanine (PMA) were synthesized and their structures were determined by single crystal X-ray crystallography. The geometry and conformation of both molecular aggregates and their hydrogen bond networks are not similar. In the PMV crystal structure, PMV and the solvent water molecule are linked by O–H⋯O intermolecular hydrogen bonds resulting in two ring motifs R₁₂¹²(48) and R₄⁴(22). A three-dimensional supramolecular structure is formed by hydrogen bonds N–H⋯O between the layers. In the PMA crystal structure, each water molecule connects three PMA molecules through O–H⋯O intermolecular hydrogen bonds, and a ring motif R₄⁴(24) is formed in the structure. But there is no hydrogen bond interaction between the layers, in which van der Waals' interaction is involved only.     

An expeditious construction of 9-membered rings

9-Membered rings are readily constructed through a radical addition-cyclisation sequence on a 1,6-dien-3-ol system followed by a Grob-type fragmentation.     

Resonance energies of fullerenes with 4-membered rings

We report the resonance energies (REs ) of several fullerenes with 4-membered rings and their isomers with only 5- and 6-membered rings computed using the conjugated-circuit model [RE (CC )] and the topological resonance energy (TRE ) model. Both aromaticity indices were normalized by dividing by the size of the considered fullerene [RE (CC )/e and TRE /e]. The results parallel the predictions by Gao and Herndon using the much more advanced SCF –UHF π-electron approach. A good linear correlation is found between the topologically defined indices [RE (CC )/e and TRE /e] and normalized SCF –UHF π-electron energy. © 1995 John Wiley & Sons, Inc.     

Direct N-arylation of 5-membered heterocyclic nitrogen rings

Ring-substituted bromoaryl derivatives are used to arylate imidazole at the NH group.For Part IV see [2].     

Synthesis of 6-, 7- and 8-membered cyclosiloxanes having multifunctional groups

Cyclosiloxanes having intramolecular donor atoms, a Si-Si bond, and vinyl groups were synthesized as useful precursors for ring-opening polymerization. 1,1,3,3-Tetrakis(dimethylaminomethylphenyl)-5,5-dimethylcyclotrisiloxane was also synthesized and characterized by single crystal X-ray structural analysis, which shows strong coordination from N to Si in the solid state.     

Fragmentation of nitrone triflates to 9-membered rings

A new fragmentative rearrangement of nitrone derivatives to form 9-membered rings is reported. The fragmentations are triggered when nitrones are treated with triflic anhydride; a C-C bond antiperiplanar to the cleaving N-O bond is activated either by an oxygen lone pair or by an electron-rich aromatic ring. In the former case, further cyclization of the 9-membered intermediate leads to a rearranged condensed ring system, but when triggered by arenes, 9-membered ring amides are isolated.     

Facile synthesis of 7-10 membered rings by intramolecular condensation using dialkylcarbonate as solvent

A convenient large-scalable synthesis of 1-benzazepines 19 as an important intermediate of CCR5 antagonist, oral HIV-1 therapy, was established. The anilination of o-halogenobenzaldehyde 9 with alkylamino-acid 16 gave o-formylaniline-acid 17. Compound 17 was esterified followed by the improved reaction using the combination of alcoholate and dialkyl carbonate in one-pot, to easily produce 19. Namely, these new processes afforded the desired product 19 in only two steps from the starting materials, as compared with the previous 10 steps. Moreover, these convenient methodologies were applied to other heterocycles to give 8-10 membered rings, such as 1-benzazocine, 1-benzazonine, and 1-benzazecine.