Formation Of Seven-membered Ring Research Articles

Gold(I)-Catalyzed Intramolecular Enantioselective Hydroarylation of Allenes with Indoles

Treatment of 2-allenyl indole 4 with a catalytic 1:2 mixture of [(S)-2]Au2Cl2 [(S)-2 = (S)-3,5-tBu-4-MeO-MeOBIPHEP] and AgBF4 in toluene at -10 degrees C for 17 h led to isolation of tetrahydrocarbazole 5 in 88% yield with 92% ee. The protocol was effective for the cyclization of terminally disubstituted allenes and for the formation of seven-membered rings.

Salicylanilide esterification: unexpected formation of novel seven-membered rings

Novel benzoxazepines were prepared upon esterification of biologically active salicylanilides with some N-protected amino acids. While the desired conjugates of the salicylanilides with the amino acids were obtained when sterically more demanding amino acids were used, benzoxazepines were formed as a result of a seven- exo-trig cyclization in the case of N-protected glycine and alanine. The structures of the products were confirmed by 2D NMR methods, and further transformations of the acyclic conjugates provided additional support for the proposed mechanism of cyclization.

Conformational structure, dynamics, and solvation energies of small alanine peptides in water and carbon tetrachloride

The rate-limiting barrier for peptide transport across lipid bilayers is the nonpolar hydrocarbon interior. Permeating peptides may undergo conformational changes during their transfer from an aqueous solution into the barrier domain, thus facilitating peptide transport. To test this hypothesis, all-atom and explicit-solvent molecular dynamics (MD) simulations have been conducted on a series of small peptides, p-toluyl-Ala(n) (n = 0-3) used previously in transport experiments, to explore their conformational structures, dynamics and solvation free energies in water and carbon tetrachloride (CCl(4)). The conformations of the p-toluyl alanine di- and tri-peptides in water were found to be far from random coils, with P(II) and alpha(R) dominating but with smaller populations of seven-membered (c(7)) and five-membered rings (c(5)). In contrast, the seven-membered ring, c(7), along with c(5) dominated in CCl(4). These results indicate that the conformational preferences of the alanine peptides are highly sensitive to solvent. Dynamically, stable seven-membered ring formation occurred on a time scale of 10 ps while larger ring-sizes (e.g., 10-membered rings) were observed much less frequently. The values of adjacent torsional angles (phi(1), psi(1)) were dependent on neighboring torsional angles. Thermal motions of neighboring torsions leading to transitions between c(7), c(5), alpha(R), and P(II) conformers were highly cooperative while longer range correlations between transitions of adjacent sets of torsions (phi(1), psi(1)) and (phi(2), psi(2)) were less evident. Peptide folding in CCl(4) lowers the intramolecular electrostatic energies. This, along with hydrophobic interactions, favors partitioning into CCl(4). These effects only partially offset other types of intramolecular interactions and peptide-solvent polar interactions that are more favorable in water, leading to net transfer free energies (3-7 kcal/mol) that disfavor peptide transfer from water into carbon tetrachloride.

An MO study of regioselective amine addition to ortho-quinones relevant to melanogenesis

Energy profiles for alternative intramolecular cyclisations of 4-(aminoalkyl)- ortho-quinones have been calculated using the AM1 method and ab initio energies of the transition states are determined. In all the cases cyclisation at position 5 occurs via a significantly lower energy transition state than cyclisation at position 3. This is consistent with experimental observations. Optimal trajectories for attack have been determined from a study of the reactions of methylamine with 4-methyl- ortho-quinone. For cyclisation of aminoalkyl derivatives deviation from the optimal direction is less for reaction at position 5 but constraint on angle of attack only partially accounts for the regioselectivity. Intrinsic differences in the electronic energies of the alternative transition states are the main contributor to regioselectivity. The relative energies of transition states can be modified by variation of the substituent at position 4. The calculations suggest that seven-membered ring formation may occur via a boat transition state and steric hindrance in the seven-membered transition states may account for the experimentally observed influence of N-substituents on the mode of reaction.

Rearrangements Encountered in the Attempted Syntheses of Pyridoazepinone Carboxylic Acids

Attempts to synthesize pyridoazepinone carboxylic acids such as 33 by standard methodologies resulted exclusively in unusual and unexpected rearrangement products. Seven-membered ring formation was attempted by ring expansion of a six-membered ring and by aldol ring closure. In each case, the major product resulted from rearrangement of the starting material without detection of the desired product. Ultimately, an isomeric pyridoazepinone ethyl ester was prepared; however, attempted saponification resulted in another unusual rearrangement. [reaction: see text]

Synthesis of the JKLM-ring fragment of ciguatoxin

A stereoselective synthesis of the LM-ring fragment has been achieved starting from a sugar derivative. A stereoselective synthesis of the JKLM-ring fragment has been achieved through a coupling between two segments via heteroconjugate addition, seven-membered ether ring formation mediated by an acetylene cobalt complex, and spiroketalization reaction.

Synthesis of JKLM Ring Fragment of Ciguatoxin via Acetylene-Cobalt Strategy

A stereoselective synthesis of the JKLM ring fragment has been achieved through a coupling between two segments via heteroconjugate addition, seven-membered ether ring formation mediated by an acetylene cobalt complex and spiroketalization reaction.

Studies Towards the Total Synthesis of Solanoeclepin A: Synthesis of the 7‐Oxabicyclo[2.2.1]heptane Moiety and Attempted Seven‐Membered Ring Formation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Studies towards the total synthesis of solanoeclepin A: synthesis of the 7-oxabicyclo[2.2.1]heptane moiety and attempted seven-membered ring formation

This paper details studies towards the total synthesis of solanoeclepin A (1), the most active natural hatching agent of potato cyst nematodes. The first goal was the preparation of the tetracyclic left-handed substructure 2 in enantiopure form. The 7-oxabicyclo[2.2.1]heptane moiety was obtained via a diastereoselective intramolecular Diels–Alder strategy by using (R)-phenylglycinol as a chiral auxiliary as pioneered by Mukaiyama. A chromium-mediated nickel-catalysed coupling of aldehyde 5 with vinyl triflate 6 gave α,β-unsaturated lactone 18 as a single stereoisomer. The seven-membered ring was expected to arise from a McMurry coupling of dialdehyde 4. Surprisingly, oxidation of diol 24 did not lead to the desired dialdehyde 4, but to the eight-membered ring lactone 25.

An allenic Pauson-Khand-type reaction: a reversal in pi-bond selectivity and the formation of seven-membered rings.

[reaction: see text] Treatment of alkynyl allenes with [Rh(CO)(2)Cl](2) results in a formal [2 + 2 + 1] cycloaddition reaction. This reaction occurs with complete regioselectivity for a variety of substrates affording only 4-alkylidene cyclopentenones in good yields. Moreover, seven-membered rings have been prepared in high yields.

Investigation of Methods for Seven-Membered Ring Synthesis: A Practical Synthesis of 4-Oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]furan-3-carboxylic Acid

Several synthetic routes to 4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]furan-3-carboxylic acid (1) are described, and the scale-up issues with each route are discussed. Seven-membered ring formation is a key issue with these syntheses, and several strategies are presented, including preparation from cycloheptane-1,3-dione, ring-expansion routes, Dieckmann cyclization, acetylene-furan [4 + 2] cycloaddition, and Friedel−Crafts cyclization. Two of the routes were scaled in the pilot plant to provide kilogram quantities of the title compound. The first scale-up route is outlined in Scheme 2 and utilizes a ring-expansion strategy to prepare cycloheptane-1,3-dione from cyclopentanone, via a [2 + 2] cycloaddition between dichloroketene and the silyl enol ether of cyclopentanone. The diketone is converted to the title compound by condensation with ethyl bromopyruvate and base, followed by acid hydrolysis. This route was efficient on laboratory scale but encountered problems upon scale-up due to a competing fragmentation pathway in the Zn/AcOH-mediated retro-aldol of cyclobutanone 11. The second, more successful scale-up route is described in Scheme 15, and involves Friedel−Crafts acylation of 3-carboethoxyfuran selectively at the 5-position. Reduction, lactonization, and hydrogenolysis provide acid 43, which is cyclized via a second Friedel−Crafts reaction to form the seven-membered ketone.

Seven-membered ring formation through Grewe-cyclization

The first example of seven-membered ring formation using Grewe-cyclization of cyclohexene derivatives ( 3b and c) yielding spiro-substituted benzo[ c]azepines ( 9b and c) is presented.

Palladium-Catalysed Synthesis of Enantiopure 1,2,4,5-Tetrahydro-1,4-benzodiazepin-3-(3H)-one Derivatives

A convenient procedure for the preparation of 1,2,4,5-tetrahydro-1,4-bezodiazepin-3-(3H)-one derivatives (S)-2 from chiral α-substituted N-n-butyl-N-(o-iodobenzyl)glycinamides (S)-1 has been developed. Seven-membered ring formation occurs through an intramolecular N-arylation catalysed by palladium and bis(phosphine) ligands. The use of chelating bis(phosphines) allows to minimize or entirely suppress carbon-2 racemisation which occurs when a mono(phosphine) ligand is used.

Complexation-Initiated Intramolecular Diels-Alder Reaction.

A complexation-initiated intramolecular Diels-Alder reaction was demonstrated for the first time. On adsorbing the alkyne-Co(2)(CO)(6) complexes having a diene and a dienophile on opposite ends of the alkyne on silica gel, the Diels-Alder reaction was accelerated and the equilibrium was shifted toward the adduct formation to a greater extent compared to that in solution. Seven-membered ring formation was apparently favorable in this system.

Synthesis of biliverdins with stable extended conformations. Part I

Biliverdins with extended conformations stabilized by intramolecular ethyl bridges were obtained by base treatment of helical biliverdins with 2-chloroethyl side chains. Thus, neobiliverdin IXβ ( 6) was obtained by reaction of 13,18-di-(2-chloroethyl)-biliverdin 5 with DBU. During the reaction the 2-chloroethyl-C(13) residue underwent an intramolecular substitution reaction with N-24 while the 2-chloroethyl-C(18) residue underwent an elimination reaction to form a vinyl residue. This reaction scheme was unambiguously demonstrated by performing the synthesis of [ 15N-24]-dihydro-neobiliverdin IXβ ( 19) and of [ 15N-23]-dihydrophorcabilin ( 31). The method was then applied to the synthesis of neobiliverdin IXδ, a natural product isolated from the ovaries of the sea snake Turbo cornutus. It was concluded that when the 2-chloroethyl side chains are at C(3) (or the equivalent C(17)) and C(2) (or the equivalent C(18)) positions of the biliverdin, elimination reactions lead to vinyl residues in basic media; at any other of the β-pyrrole sites, treatment with base leads to the formation of seven-membered rings by intramolecular substitution reactions.

From sugars to carbocycles. 4. Exclusive seven-membered ring formation from D-glucose

An example of the 1,3-dithiane methodology of carbocyclization of sugars leading selectively to a seven-membered ring 16 is presented. The selectivity is discussed in terms of steric hindrance of the respective six-memberd transition states.

Pd-Catalyzed Cycloaddition of Vinylcyclopentenes with Trimethylenemethane. Substituent Effect on [4+3] vs [3+2] Selectivity

Abstract The Pd-catalyzed reaction of 2-vinylcyclopentenes 2 and 3 with trimethylenemethane gave [4+3] and [3+2] cycloadducts. Derivatization of 2-vinylcyclopentenones with bulky ketal substituents served to enhance seven-membered ring formation.

Intramolecular addition of vinyl and aryl radicals to oxime ethers in the synthesis of five-, six- and seven-membered ring systems

The oxime ethers 2a–e have been cyclised with Bu3SnH to the alkoxyamino-3-methylidenechromanes 3a–e. Seven-membered ring formation was observed when the oxime ethers 7a, b were converted into the dibenzo[b,e]oxepines 8a, b under similar conditions. 1-Methoxyaminoindanes 12a, b were produced from the cyclisation of the substrates 11a, b and the cis-fused cyclic products 15a, b and 18 were obtained from compounds 14a, b and 17, respectively.

An IETS study of the adsorption of 1,2-, 1,3- and 1,4-benzenedimethanol, 2-, 3- and 4-hydroxyphenethyl alcohol, and 2-, 3- and 4-hydroxybenzyl alcohol, on thin-film plasma-grown aluminium and magnesium oxides

Abstract The IET spectra of 1,2-benzenedimethanol and 2-hydroxyphenethyl alcohol adsorbed on thin-film aluminium and magnesium oxide suggest that seven-membered chelate ring formation is probable at both oxide surfaces. In like manner, 2-hydroxybenzyl alcohol adsorption may involve six-membered chelate ring formation at both the aluminium and magnesium oxide surfaces. For the analogous meta -substituted systems, i.e. 1,3-benzenedimethanol, 3-hydroxyphenethyl alcohol and 3-hydroxybenzyl alcohol, the IET spectra suggest that the surface adsorption—chemisorption process follows a similar pattern to that of the 1,2-systems, though now the 1,3-disposition of the functional groups precludes chelated geometries at the oxide surface under examination. Of the corresponding 1,4-molecules only 1,4-benzenedimethanol was found to bind to either oxide. The IET spectra for this adsorbate do not indicate clearly the mode of adsorption at the oxide surfaces other than to suggest that either only one end of the molecule is chemisorbed leaving the “free” hydroxyl group to contribute to the background ν(OH) signal of each oxide or both methanolic hydroxyl groups are interacting with the oxide surfaces. These alternatives separately or in combination cannot be distinguished further.

Preparation of heterocyclic dications from substituted phthalazinones

Using perchloric acid 2-(ω-hydroxyalkyl)-4-(ω)'-hydroxyalkyl~ amino)phthalazinones and their 6,7-dimethoxy derivatives were converted into tetracyclic dications containing both iminoether and amidine moieties The 2-(4~hydroxyt)utyl) chain avoided the formation of seven-membered ring with either isomerisation or degradation involving cleavage of C-N bond assisted by neighbouring group participation of the hydroxyl group. The sequence of ring closures depends on the ring substituents and the lengths of side chains. The reaction mechanism is also influenced by the site of the protonation. The structures of the new tetracycles were proved by 1H- and 13C-nmr spectroscopy.