Five-membered Carbocyclic Ring Research Articles

Front Cover: Metallocene Anions: From Electrochemical Curiosities to Isolable Complexes (Eur. J. Inorg. Chem. 11/2022)

The Front Cover shows a depiction of a classical metallocene anion, with a red metal atom in a formal +I oxidation state sandwiched by two cyclopentadienyl rings. The central image is flanked by a range of d-transition metal(I) ions, together with a selection of derivatized five-membered carbocyclic rings, representing the d-block metallocene anions that have been structurally authenticated to date. The review covers the chemistry of metallocene anions and their derivatives, focusing on d-block examples, and provides a historical overview from their detection as intermediates in low-temperature electrochemical studies to the most recent examples of isolated complexes. The cover was designed by Corentin Magnoux. More information can be found in the Review by C. Magnoux and D. P. Mills.

Artapilosines A and B, Unusual Phenanthrene Derivatives Related to Aporphine Alkaloids from Artabotrys pilosus.

Two unusual phenanthrene derivatives related to aporphine alkaloids, artapilosines A (1) and B (2), as well as two biogenetically related known aporphine alkaloids, (-)-anonaine (3) and (-)-N-acetylanonaine (4), were separated and purified from Artabotrys pilosus. Artapilosine A (1) is the first compound representative of a new class of phenanthrene derivatives having an unprecedented carbon skeleton, in which the six-membered nitrogen-containing heterocyclic structure in a typical aporphine alkaloid was substituted with a unique five-membered carbocyclic ring. This is the first report of the formation of a carbon-carbon bond between C-5 and C-6a in 1 with the loss of the nitrogen atom N-6 in the classic aporphine alkaloid. Artapilosine B (2) is a novel phenanthrene derivative having a hydroxyethyl as a substituent on the phenanthrene ring. Their chemical structures as well as absolute configurations were determined based on analysis of spectroscopic data. Additionally, the potential anti-HIV activities of all isolates 1-4 were appraised. Artapilosines A (1) and B (2) showed notable anti-HIV reverse transcriptase affects, with EC50 values of 20.93 and 125.29 nM, respectively. These results suggested that the discovery of these novel phenanthrene derivatives from A. pilosus with remarkable anti-HIV effects could be essentially important for the researching and developing of new anti-HIV agents.

Synthesis of six-membered carbocyclic ring α,α-disubstituted amino acids and arginine-rich peptides to investigate the effect of ring size on the properties of the peptide

Cell-penetrating peptides (CPPs) have been attracting attention as tools for intracellular delivery of membrane-impermeant functional molecules. Among the variety of CPPs that have been developed, many are composed of both natural and unnatural amino acids. We previously synthesized α,α-disubstituted α-amino acids (dAAs) containing a five-membered carbocyclic ring in its side chain and revealed the utility of dAAs for the development of novel CPPs. In the present study, we designed a six-membered carbocyclic ring dAA with an amino group on the ring and introduced it into arginine (Arg)-rich peptides to further investigate the value of dAAs for developing CPPs. We also assessed the effects of the size of the dAA carbocyclic ring on cellular uptake of dAA-containing peptides. The stability of the peptide’s secondary structure and its membrane permeability were both greater in dAA-containing peptides than in an Arg nonapeptide. However, the number of carbon atoms in the dAA side chain ring had little effect. Nevertheless, these results show the utility of cyclic dAAs in the design of novel CPPs containing unnatural amino acids.

Density functional theory studies onthe generation of trimethylenemethanes from the ring opening of dialkoxymethylenecyclopropanes and methylenecyclopropanethioacetals and follow-up reactions.

This work reports a detailed DFT study on the generation of trimethylenemethanes (TMMs) from the ring opening of dialkoxymethylenecyclopropane (DMCP), methylenecyclopropanethioacetal (MCPT), and substituted derivatives of DMCP and MCPT, as well as follow-up reactions of the TMMs. The singlet DMCP and MCPT were found to be 51.32 and 53.77kcal mol-1 more stable than the triplet DMCP and MCPT respectively, corresponding to triplet:singlet population ratios of 1:1038 and 1:1040, respectively, at 25°C using Boltzmann distribution, implying that the proportion of the triplet species is negligible at 25°C. The ring-opening reactions occur through singlet transition states with barriers of 40.68 and 42.27kcal mol-1 for DMCP and MCPT, respectively, and yield TMMs that are very unstable compared to the precursors, with the triplet TMM being far more stable than the singlet. Whereas the singlet TMMs readily undergo cycloaddition reactions with olefins to form five-membered carbocyclic rings, the triplet species do not. The selectivity of the reactions of the DMCP TMMs is very sensitive to temperature; at 25°C, cycloaddition with olefins and ring-closure to form ketenes have very comparable barriers while temperatures above 150°C favor the exclusive formation of a ketene followed by dimerization. In MCPT, ring closure toform ketenes is thefavored reactionat all temperatures studied. Pathways for the generation of trimethylenemethanes from their precursors and follow-up reactions.

Illisimonin A, a Caged Sesquiterpenoid with a Tricyclo[5.2.1.01,6]decane Skeleton from the Fruits of Illicium simonsii.

Illisimonin A, an unprecedented sesquiterpenoid with a tricyclo[5.2.1.01,6]decane skeleton, was isolated from the fruits of Illicium simonsii. The structure and absolute configuration of 1 were determined using extensive spectroscopic evidence and electronic circular dichroism (ECD) calculations. It was determined that 1 possesses a caged 2-oxatricyclo[3,3,0,14,7]nonane ring system fused to a five-membered carbocyclic ring and a five-membered lactone ring. A plausible biogenetic pathway for 1 was proposed, and 1 showed neuroprotective effects against oxygen-glucose deprivation (OGD)-induced cell injury in SH-SY5Y cells with an EC50 value of 27.72 μM.

Microwave-assisted organocatalysis: phosphine-mediated Tomita Zipper cyclization affording functionalized spirooxindole

A microwave-assisted and phosphine-mediated Tomita Zipper cyclization of dicyanomethylideneoxindoles and ynones has been developed. Various functionalized spirooxindoles with five-membered carbocyclic ring can be obtained in moderate to good yields with moderate to excellent diastereoselectivities through in situ generation of α-nucleophile (up to 87% yield, >20:1dr).

Synthesis of chiral five‐membered carbocyclic ring amino acids with an acetal moiety and helical conformations of its homo‐chiral homopeptides

Chiral five-membered carbocyclic ring amino acids bearing various diol acetal moieties were synthesized starting from l-malic acid, and homo-chiral homopeptides composed of cyclic amino acid (S)-Ac5 c(3EG) bearing an ethylene glycol acetal, up to an octapeptide, were prepared. A conformational analysis revealed that (S)-Ac5 c(3EG) homopeptides formed helical structures. (S)-Ac5 c(3EG) homopeptides, up to hexapeptides, formed helical structures without controlling the helical screw direction, while (S)-Ac5 c(3EG) hepta- and octapeptides formed helical structures with a preference for the left-handed (M) helical-screw direction. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 555-562, 2016.

Cyclization of 1,4-dihydroxyanthraquinone with α,β-unsaturated aldehyde: a new strategy for the synthesis of cyclopentanoids

A cascade cyclization strategy has been developed for the synthesis of cyclopentane-fused anthraquinones through the condensation of 1,4-dihydroxyanthraquinone with α,β-unsaturated aldehydes in the presence of common inorganic base NaOH. These fused-tetracyclic anthraquinone products are formed in a single step from readily accessible starting materials under very mild conditions without the use of any expensive or complex reagents. This method represents an unprecedented example of a base-promoted protocol to access five-membered carbocyclic rings in a single step. Moreover, this chemistry also provides useful guidance for the preparation of 6,5-fused ring systems.

Synthesis and Electrochemical Properties of Carbocyclic and Heterocyclic Diazulenylethenes

An efficient two-step method was developed for the synthesis of 1,2-di(azulen-1-yl)ethenes 15–17, having the double bond included in a five-membered carbocyclic or heterocyclic ring. The method involves preparation of the appropriate diketone precursors through Vilsmeier–Haack or Friedel–Crafts reactions, followed by their McMurry cyclization. Alkenes 16 and 17 were quantitatively converted into the corresponding dehydro derivatives 24 and 25, respectively, by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The electrochemical properties of compounds 15–17, 24 and 25 were examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), and the relationship between their structure and electrochemical behavior was established.

An unusual diepoxyguaianolide from Stevia tomentosa

The aerial parts of Stevia tomentosa afforded a new guaianolide which was characterized by physical and spectroscopic data as (−)-1,5:3,4-diepoxyguaia-10(14)-en-12,8-olide (1). The absolute configuration of this unusual compound containing two β-oriented epoxide groups in the five-membered carbocyclic ring, one located at the C-1 and C-5 ring junction, was established as (1S,3S,4S,5R,7R,8R,11S)-1 by vibrational circular dichroism spectroscopy in combination with density functional theory calculations, and by evaluation of Flack and Hooft X-ray parameters.

7′-[4-(Trifluoromethyl)phenyl]-5′,6′,7′,7a'-tetrahydrodispiro[indan-2,5′-pyrrolo[1,2-c][1,3]thiazole-6′,2′′-indan]-1,3,1′′-trione

In the title compound, C29H20F3NO3S, the thia­zolidine ringadopts a half-chair conformation. The pyrrolidine and two five-membered carbocyclic rings are in envelope conformations with the spiro C atoms at the flaps. The trifluoro­methyl-substituted benzene ring forms dihedral angles of 62.37 (14) and 87.40 (14)° with the benzene rings of the dihydro-1H-indene units. The two benzene rings form a dihedral angle of 36.94 (15)°. The mol­ecular structure is stabilized by intra­molecular C—H⋯O hydrogen bonds, which generate S(6) ring motifs. In the crystal, mol­ecules are linked into inversion dimers by pairs of inter­molecular C—H⋯O hydrogen bonds, generating R 2 2(10) ring motifs.

7′-(4-Bromophenyl)-5′,6′,7′,7a'-tetrahydrodispiro[indan-2,5′-pyrrolo[1,2-c][1,3]thiazole-6′,2′′-indan]-1,3,1′′-trione

In the title compound, C28H20BrNO3S, the thia­zolidine, pyrrolidine and two five-membered carbocyclic rings are in envelope conformations. The bromo-bound phenyl ring forms dihedral angles of 61.97 (18) and 88.30 (17)° with the other two benzene rings. The two benzene rings form a dihedral angle of 30.3 (2)°. The mol­ecular structure features an intra­molecular C—H⋯O hydrogen bond, which generates an S(6) ring motif. In the crystal, mol­ecules are linked into inversion dimers by pairs of C—H⋯O hydrogen bonds.

7′-Phenyl-5′,6′,7′,7a′-tetrahydrodipiro[indan-2,5′-pyrrolo[1,2-c][1,3]thiazole-6′,2′′-indan]-1,3,1′′-trione

The asymmetric unit of the title compound, C28H21NO3S, contains two mol­ecules with similar geometries. The thia­zolidine rings adopt half-chair conformations while the pyrrolidine and the diketo-substituted five-membered carbocyclic rings are in envelope conformations with the spiro C atoms at the flaps. In one mol­ecule, the phenyl ring forms dihedral angles of 57.76 (12) and 71.79 (12)° with the fused benzene rings and the fused benzene rings form a dihedral angle of 57.75 (13)°. The corresponding dihedral angles in the other mol­ecule are 60.04 (12), 72.93 (12) and 54.51 (13)°. The mol­ecular structure is stabilized by intra­molecular C—H⋯O hydrogen bonds, which generate S(6) ring motifs. In the crystal, mol­ecules are linked via C—H⋯O and C—H⋯N hydrogen bonds into layers lying parallel to the ab plane.

Trimethyl-3-methoxy-4-oxo-5-triphenylphosphoranylidenecyclopent-1-ene-1,2,3-tricarboxylate

The title compound, C30H27O8P (2), was formed as one of two products {(1) [Krawczyk et al. (2010 ▶). Acta Cryst. E66 (cv2752)] and (2)} in the reaction of dimethyl acetyl­enedicarboxyl­ate with triphenyl­phosphine. The mol­ecule of (2) consists of a five-membered carbocyclic ring. The P atom is a part of a triphenylphosphoranylidene substituent. In contrast to (1), the five-membered ring of (2) is planar, the r.m.s. deviation being only 0.009 (2) Å.

ChemInform Abstract: The Use of Fischer Carbene Complexes for the Preparation of Five-Membered Carbocyclic Rings

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Synthesis of cyclopentenones from cyclopropanes and silyl ynol ethers.

Synthesis of cyclopentenones from cyclopropanes and silyl ynol ethers.

5-(1H-Inden-2-yl)-1,3-benzodioxole

In the title compound, C16H12O2, the non-H atoms are coplanar with a mean r.m.s. deviation of 0.0260 (2) Å. The deviations of the bond angles from normal values at the indenyl junction C atom and the indenyl bridgehead C atom nearest the junction are imposed by the five-membered ring geometry. Due to conjugation, the single bond linking the two ring systems [1.455 (3) Å] is significantly shorter than the formal single bonds in the five-membered carbocyclic ring [1.500 (3) and 1.489 (3) Å].

Functionalized Alkali Metal Cyclopentadienides: Structural and Chemical Features

Synthetic routes to alkali metal cyclopentadienides that bear various organic functional groups on their five-membered carbocyclic ring systems are presented and discussed using selected examples. These include carbonyl addition reactions of cyclopentadienides to, for example, alkyl isocyanates to eventually yield carboxamide-substituted cyclopentadienide systems. These and related routes have been used to, for example, prepare peptide-substituted Cp anions. Fulvene routes are very useful for the synthesis of alkenylcyclopentadienides, of imino-Cp compounds, of aminomethyl- or phosphinomethyl-Cp derivatives, and even their respective dianionic analogues. Many of the new functionalized lithium cyclopentadienide examples were structurally characterized. Many of them form well-defined extended oligomeric structures that make specific use of the functional groups in the construction of the supramolecular complex framework. Eventually, first examples of specific carbon−carbon coupling reactions are presented a...

Porphyrins with exocyclic rings. Part 22: Synthesis of deoxophylloerythroetioporphyrin (DPEP), three ring homologues, and five related nonpolar bacteriopetroporphyrins using a western ring closure and an improved b-bilene methodology

Dipyrrolic intermediates incorporating five-membered carbocyclic rings are easily prepared from cyclopenta[ b]pyrroles, and this unit represents the southern half of the DPEP-type geoporphyrins found in organic-rich sediments such as oil shales and petroleum. Related dipyrroles with six-, seven- or eight-membered carbocyclic rings were shown to give b-bilenes when reacted with dipyrrylmethane carbaldehydes under mildly acidic conditions. Following deprotection of the terminal ester groups, cyclization with TFA–CH(OMe) 3 gave a series of ring homologues of deoxophylloerythroetioporphyrin (DPEP). The b-bilenes generated from the five-membered ring dipyrroles proved to be rather unstable and had to be used directly without purification. Cyclization gave DPEP contaminated with an etioporphyrin by-product, but these could be separated as the nickel(II) derivatives by flash chromatography. This approach gave superior yields of DPEP compared to previously reported methods. In addition, the methodology could be extended to the synthesis of related petroporphyrins, and a series of five molecular fossils derived from bacteriochlorophylls d were synthesized by this approach.

Preparation of Dinuclear Vinylidene Complexes and Their New Deprotonation Reactions

The dinuclear dicationic vinylidene complex {[Ru]CC(Ph)CH2C(CH2CN)C[Ru]}2+ (7a, [Ru] = Cp(PEt3)2Ru) is prepared from the reaction of ICH2CN with {[Ru]CC(Ph)CH2C⋮C[Ru]}+ (6a). Deprotonation of 7a by n-Bu4NOH is followed by a cyclization process yielding the stable complex 9a, containing a five-membered carbocyclic ring ligand, which is fully characterized by 2D-NMR analysis and a single-crystal X-ray diffraction analysis. Similarly deprotonation of {[Ru]CC(Ph)CH2C(CH2COOEt)C[Ru]}2+ (8a) gave the stable product 11a containing a bridging ligand also with a similar five-membered carbocyclic ring. The cyclization process is affected by an ancillary ligand on the Ru metal center. Thus the analogous dinuclear complex 9b, with a bistriphenylphosphine ligand on one metal, which is prepared in a similar manner from {[Ru]CC(Ph)CH2C(CH2CN)C[Ru‘]}2+ (7b, [Ru‘] = Cp(PPh3)2Ru), is unstable, undergoing isomerization to give the dinuclear complex 10b, containing a cyclopropenyl ligand.