Ring expansion of 11H-benzo[b]fluorene-11-methanols and related compounds leading to 17,18-diphenyldibenzo[a,o]pentaphene and related polycyclic aromatic hydrocarbons with extended conjugation and novel architectures

Condensation between 7-(1,1-dimethylethyl)-13-phenyl-8H-indeno[2,1-b]phenanthrene and paraformaldehyde produced the corresponding 9-fluorenylmethanol derivative, which on treatment with P₂O₅ to promote a Wagner-Meerwein rearrangement for ring expansion furnished 14-phenyldibenzo[a,j]anthracene in 88% yield. Similarly, 17,18-diphenyldibenzo[a,o]pentaphene possessing a helical twist and bearing two phenyl substituents at the most sterically congested C17 and C18 positions and other related compounds were likewise synthesized. Subsequent intramolecular arylation reactions involving the phenyl substituents produced polycyclic aromatic hydrocarbons with novel architectures.     

Efficient strategy for convergent synthesis of trans-fused polycyclic ethers based on an intramolecular SmI2-promoted cyclization of iodo ester

An efficient convergent strategy for the construction of a trans-fused 6-6-6-6-membered tetracyclic ether ring system was developed. The key steps involve coupling of two cyclic ethers by esterification, SmI₂-promoted intramolecular reductive cyclization of iodo ester to hemiacetal, dehydration to dihydropyran, hydroboration, oxidation, intramolecular acetalization, and Lewis-acid catalyzed silane reduction.     

Access to the noryohimban [6,5,6,5,6] ring system via an intramolecular furan Diels-Alder reaction

Polycyclic indolic compounds containing the [6,5,6,5,6] ring system were prepared via an intramolecular furan Diels-Alder reaction of α,β-unsaturated amides generated by the N-acylation of 1-(2-furyl)-β-tetrahydrocarbolines. This chemistry can provide access to D(14)-noryohimban derivatives by exploiting the functionality on the C,D,E ring system of the corresponding cycloadducts.     

New data on the reaction of hexafluorothioacetone with styrenes

Hexafluorothioacetone, generated in situ from its cyclic dimer (1) in the presence of CsF catalyst was shown to react with styrene or 4-alkyl-styrenes (alkyl = c-hexyl, Me, t-Bu) forming the corresponding 2:1 Diels-Alder cycloadducts as major products. All cycloadducts were isolated, and the structure of two of them was established by single crystal X-ray diffraction. While 2-vinylnaphthalene, 4-CF₃- and 4-Cl-styrenes in the presence of CsF catalyst react with 1 producing the corresponding 1:1 Diels-Alder cycloadducts, 4-alkoxy styrenes were found to produce preferentially the corresponding thietanes. The reaction of styrenes with 1 was also found to be sensitive to the source of fluoride ion and the solvent.     

Titanium-catalyzed [6π+2π]-cycloaddition of Si-containing alkynes to bis(1,3,5-cycloheptatriene-7-yl)alkanes

The reaction between Si-containing alkynes and bis(1,3,5-cycloheptatriene-7-yl)alkanes in the presence of the two-component catalyst Ti(acac)₂Cl₂-Et₂AlCl, led to the selective formation of mono- and bis-adducts – {9-[4-(2,4,6-cycloheptatrienyl)alkyl]-8-alkyl(phenyl)bicyclo[4.2.1]nona-2,4,7-triene-7-yl}(trimethyl)silanes and bis(7-trimethylsilyl-8-alkyl(phenyl)bicyclo[4.2.1]nona-2,4,7-triene-7-yl)alkanes in 78–86% yield. The structures of the obtained cycloadducts were confirmed by ¹H and ¹³C NMR spectroscopy.     

Synthesis of N-substituted carbazolones from α-iodo enaminones via Pd(0)-catalyzed intramolecular coupling under microwave irradiation

A variety of N-aryl and N-alkyl carbazolones were conveniently achieved in good to high yields via Pd₂(dba)₃-mediated intramolecular coupling of N-substituted α-iodo enaminones under microwave irradiation. The Pd(0)-catalyzed cyclization was found to proceed favorably with the more electron-deficient phenyl ring during the reactions involving unsymmetrical N,N-diaryl α-iodo enaminones. This unique property enables the construction of carbazolone skeleton containing nitro substituted benzenoid ring.     

Synthesis of pyrrolo[3,4-b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4-b]pyrrole and its N-1-C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.     

Cinnamoyl shikonin

The title compound, 1-(5,8-di­hydro-1,4-di­hydroxy-5,8-dioxo-2-naphthyl)-4-methyl­pent-3-en-1-yl cinnamate, C₂₅H₂₂O₆, crystallizes in space group P2₁. The phenyl ring of the cinnamate is anti to the carbonyl group of the same moiety [C—C—C—C = −175.6 (2)°] and is nearly parallel to the naphthyl ring system. Two six-membered rings formed by intramolecular hydrogen bonds, with O—H⃛O distances of 2.587 (2) and 2.589 (2) Å, occur on either side of the fused ring system, creating a tetracyclic pyrene-shaped system. The phenyl ring forms an intermolecular stack with the benzo­quinone ring, as a result of aromatic π–π interactions.     

Conformational Analysis of N-Alkyl-N-[2-(diphenylphosphoryl)ethyl]amides of Diphenylphosphorylacetic Acid: Dipole Moments,IR Spectroscopy,DFT Study

Experimental and theoretical conformational analysis of N-methyl-N-[2-(diphenylphosphoryl)ethyl]diphenylphosphorylacetamide, N-butyl-N-[2-(diphenylphosphoryl)ethyl]diphenylphosphorylacetamide, and N-octyl-N-[2-(diphenylphosphoryl)ethyl]diphenylphosphorylacetamide was carried out by the methods of dipole moments, IR spectroscopy, and Density Functional Theory (DFT) B3PW91/6-311++G(df,p) calculations. In solution, these N,N-dialkyl substituted bisphosphorylated acetamides exist as a conformational equilibrium of several forms divided into two groups—with Z- or E-configuration of the carbonyl group and alkyl substituent, and syn or anti arrangement of the phosphoryl-containing fragments relative to the amide plane. The substituents at the phosphorus atoms have eclipsed cis- or staggered gauche-orientation relative to the P=O groups, and cis orientation of the substituents is due to the presence of intramolecular H-contacts P=O...H−C_phenyl or p,π conjugation between the phosphoryl group and the phenyl ring. Preferred conformers of acetamides molecules are additionally stabilized by various intramolecular hydrogen contacts with the participation of oxygen atoms of the P=O or C=O groups and hydrogen atoms of the methylene and ethylene bridges, alkyl substituents, and phenyl rings. However, steric factors, such as a flat amide fragment, the bulky phenyl groups, and the configuration of alkyl bridges, make a significant contribution to the realization of preferred conformers.     

The fragmentations of substituted cinnamic acids after electron impact

The fragmentations of a number of cinnamic acids substituted at the phenyl ring have been studied with the aid of 70 eV mass spectra and mass analysed ion kinetic energy spectra. Evidence is presented that the formation of [C₉H₇O₂]⁺ ions occurs by intramolecular aromatic substitution reactions. A mechanism is proposed for the energetically favourable loss of the substituents from meta and para positions of the phenyl ring. The analytical use of intramolecular aromatic substitution reactions is briefly discussed.     

Cyclization versus oligomerization of SP- and RP-5′-OH-N-benzoyl-2′-deoxycytidine-3′-O-(2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane)s

The S_P-isomer of 5′-OH-N⁴-benzoyl-2′-deoxycytidine-3′-O-(2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane) undergoes DBU-promoted intramolecular cyclization providing as a sole product S_P-deoxycytidine cyclic 3′,5′-O,O-phosphorothioate. Unexpectedly, the R_P-counterpart yields a mixture of products consisting of R_P-deoxycytidine cyclic 3′,5′-O,O-phosphorothioate and macrocyclic oligo(deoxycytidine phosphorothioate)s. The results of molecular modeling indicate that the dychotomy observed for the R_P substrate may result from remarkably higher energy of the corresponding transition states, caused by the presence of bulky ‘spiro’ pentamethylene substituent at the position C4 in the oxathiaphospholane ring.     

Asymmetric synthesis of 1-azaspiro[4.5]decanes via intramolecular dipolar cycloaddition of nitrones containing the bornane-10,2-sultam chiral auxiliary

The intramolecular 1,3-dipolar cycloaddition of a cyclic nitrone, prepared by an asymmetric electrophilic enolate hydroxyamination using the (2R)-bornane-10,2-sultam chiral auxiliary, proceeds to give bridged and fused cycloadducts with total diastereocontrol. Reduction of the fused isoxazolidine provides a 1-azaspiro[4.5]decane as a potential intermediate in the asymmetric synthesis of the cylindricine alkaloids.     

X=y-zh systems as potential 1,3-dipoles—5 : Intramolecular cycloadditions of imines of α-amino acid esters

Azomethine ylides are readily generated from imines of α-amino acid esters by a formal 1,2-H shift. A suitably positioned unactivated double or triple bond in either of the two precursors of the imines (aldehyde or α-amino ester) leads to an intramolecular cycloaddition generating fused ring systems in good yield. Cis stereochemistry is assigned to the newly created ring junction of the cycloadducts based on NOE difference spectroscopy and, in the case of 8a, by a single crystal X-ray structure. Equilibration of the kinetically formed dipole leads to mixtures of epimeric cycloadducts for imines of phenylglycine methyl ester but equilibration is not observed for other imines. Reasons for this are discussed. The intramolecular cycloaddition is sensitive to ring size with 6/5 and 5/5 cis-fused systems being most easily formed depending in which moiety (aldehyde or amino acid) the dipolarophile is located. Intramolecular trapping of the azomethine ylide by an alkyne is accompanied by variable amounts of aromatized pyrrolic products.     

Rotational isomerism—22: An nmr study of oh..π bonding and the conformations of benzyl alcohol and derivatives

The conformations of benzyl alcohol, the ortho and para nitro and methoxy derivatives and benzyl methyl ether have been investigated by NMR in CCL₄ and DMSO solutions. The ³J(CH.OH) and ²J(H.C.H) couplings (the latter via the ²J(H.C.D)coupling)and the OH chemical shift (in DMSO and ∞ dil^XXX as conformational probes. The δ_∞ (OH) for ROH (R = Me, Et, iPr) is also given.The results provide no support for the existence of an intramolecular H-bond in benzyl akohol The endo conformation of the OH proton (anti to a CH proton) is favoured by ca. 1 kcal mole^?1 over the exo conformation (H anti to phenyl) and these conformers are responsible for the separate OH frequencies observed in the IR spectrum. The results do not support an extreme conformation of the phenyl ring (C.C.C.O dihedrals of 0 or 90°) but are consistent with either an 6?0° conformation of the phenyl ring or a freely rotating model. In ortho nitrobenzyl alcohol intramolecular H-bonding is present, but in ortho methoxy benzyl alcohol little or no bonding to the substituent occurs.     

Synthesis of D2 receptor ligand analogs incorporating one dicarba-closo-dodecaborane unit

Boron clusters, and especially dicarba-closo-dodecaboranes, can be used as hydrophobic pharmacophores in the design of new drugs and radiotracers. In the current Letter, analogs of enantiomeric substituted benzamides (Raclopride and FLB-457) in which the phenyl ring has been substituted by a carborane cage (either orto- or meta-carborane) have been developed as potential D₂ receptor antagonists. The formation of intramolecular hydrogen bonds (in solution) and the stability of the new chemical entities have been evaluated by means of ¹H NMR and HPLC-MS, respectively.     

X=Y-ZH compounds as potential 1,3-dipoles. Part 64: Synthesis of highly substituted conformationally restricted and spiro nitropyrrolidines via Ag(I) catalysed azomethine ylide cycloadditions

1,3-Dipolar reactions of imines of both acyclic and cyclic α-amino esters with a range of nitroolefins using a combination of AgOAc or Ag₂O with NEt₃ are described. In most cases the reactions were highly regio- and stereospecific and endo-cycloadducts were obtained in good yield. However, in a few cases the initially formed cycloadducts underwent base catalysed epimerisation. The stereochemistry of the cycloadducts was assigned from NOE data and established unequivocally in several cases by X-ray crystallography.     

A hydrogen pump: Transfer of four hydrogens from a cyclohexane ring to a triple bond during a menthofuran/bromoacetylene adduct rearrangement

The cycloadducts of menthofuran with acylbromoacetylenes, (3-bromo-1,6-dimethyl-5,6,7,8-tetrahydro-2H-2,4a-epoxynaphthalen-4-yl)(aryl)methanones, rearrange (CHCl₃, reflux, 1 h) to 2-(2-acylethyl)benzofurans (along with the expected 2-bromo-3-hydroxy-4,7-dimethyl-5,6,7,8-tetrahydronaphthalene-1-yl)(aryl)methanones) via 2-acylethynylmenthofurans, thus indicating the exceptionally mild and rapid transfer of four hydrogens from a cyclohexane ring to a triple bond through the furan moiety in the key intermediate 2-acylethynylmenthofuran.     

Addition reactions of heterocycles. VI. Reactions of 1,2-dimethylpyrrole and 1-methyl-2-carbomethoxypyrrole with nitrilimines

Addition reactions of 1,2-dimethylpyrrole and 1-methyl-2-carbomethoxypyrrole with C-acetyl-N-phenylnitrilimine, have been investigated. 1,2-Dimethylpyrrole gives three different types of adducts: i.e. bis-cycloadducts (Vc) and (VIc), spirocycloadduct (IX), and non cyclic bis-adduct (XII). On the other hand, 1-methyl-2-carbomethoxypyrrole gives the bis-cycloadduct (VIb) only. Compound XII arises probably through a double 1,3-addition reaction, whereas the formation of cycloadducts Vc, VIc, and IX depends on the substituents present at C₂ of the pyrrole ring and consequentially on the intermediary occurence of mono-cycloadduct (IIIc), its methylenic tautomer VII, VIc, and XL The behaviour of the cycloadducts towards heating or acidic treatment showed a termal cleavage of the pyrazoline ring and acidic cleavage of the pyrrolidine ring.     

Peracid-induced ring opening of some hexahydro-2H-isoxazolo[2,3-a]pyridines to second-generation cyclic aldonitrones

A study of the stereo- and face selectivity of the cycloaddition reactions of several mono- and disubstituted alkenes with 4-hydroxymethyl-3,4,5,6-tetrahydropyridine 1-oxide has been carried out. The addition reactions have displayed a very high degree of face selectivity in the range 13-48:1. Use of dimethyl methylenemalonate as a protective group in nitrone cycloaddition reactions has been demonstrated. The invertomeric analysis revealed that the bicyclic cycloadducts remain predominantly as the cis-fused isomer, which leads to the formation of synthetically important second-generation cyclic aldonitrones via peracid oxidation. One interesting finding was that treatment of the cycloadducts with two equivalents of peracid afforded the cyclic N-hydroxy lactams, presumably via further oxidation of the aldonitrones. The piperidine ring has been elaborated by cycloaddition reaction of the second-generation nitrones with several alkenes, which in most cases gave the cycloadducts in a stereoselective manner.     

Liquid-liquid extraction of copper(I) by cyclic tetrathio ethers

The liquid-liquid extraction of copper(I) with 12-, 13-, 15- and 16-membered cyclic tetrathio ethers ([n]aneS₄, where n represents the total number of carbon and sulphur atoms in the cyclic ligand ring) was examined stoichiometrically using picrate ion (Pic^?) for the formation of the ion pair. Copper(I) was extracted with four ligands (L) into 1,2-dichloroethane as the ion-pair compound, [Cu(I)L]⁺Pic^?. The extraction constant, K_ex, with each ligand was determined. As the ring size of cyclic tetrathio ethers increases, the log K_ex values, including that previously reported for [14]aneS₄, increase from 7.7 to 9.4. The value of Δ log K_ex, which represents the increase in log K_ex due to the addition of one carbon atom to the macrocyclic ring, was large between [13]aneS₄ and [14]aneS₄ (Δ log K_ex=1.0) and small between [14]aneS₄ and [15]aneS₄ (Δ log K_ex=0.1).