Synthesis and properties of π-extended fluoranthene derivatives from 1,2-diarylacenaphthylene derivatives

Acenaphthylene units work as a useful platform for the synthesis of polycyclic aromatic hydrocarbons (PAH). Three 1,2-diarylacenaphthylene derivatives (9-phenanthryl, 7-t-butyl-2-pyrenyl and 2-naphthyl) were prepared by Suzuki-Miyaura coupling of 1,2-dibromoacenaphthylene with the corresponding boronic acids and ester. The Scholl reaction of the phenanthryl derivative affords a donor-acceptor type fluoranthene derivative possessing a hemi-coronene structure by forming two CC bonds between phenanthryl groups. The reaction of the pyrenyl derivative allows one CC bond formation to give a helicene-type fluoranthene derivative. The reaction of the naphthyl derivative provides an asymmetric fluroranthene derivative having an anthracene unit accompanied with one CC bonding reaction, while a photochemical cyclization followed by dehydroaromatization reaction of the compound gives a symmetric fluoranthene derivative with a [5]helicene structure.     

Advances in amide and thioamide assisted C(sp3)H functionalization

CH activation is gaining substantial attention from synthetic and process chemists in recent years. Regio- and stereo-selective CH functionalization particularly facilitated by carboxylic acids and derivatives as directing groups has been progressing to an extent that this transformation could be conceived as one of the steps to assemble molecules in modern retrosynthetic analysis. This digest paper covers the most recent developments in C(sp³)H functionalization using carboxylic acid derivatives such as amides or thioamides as a directing group and highlights new reaction discoveries and applications. The content of this review is organized based on the types of directing groups and the mechanism by which the C(sp³)H bond is believed to be activated.     

Rhodium-catalyzed CH activation/cyclization of enaminones with sulfoxonium ylides toward polysubstituted naphthalenes

A rhodium-catalyzed ortho-CH functionalization and annulation between enaminones and sulfoxonium ylides was developed, affording a series of multi-substituted naphthalenes in good to moderate yields with excellent functional group compatibility. The procedure featured with enaminone acting as both a directing and cyclization bifunctional group, and the application of sulfoxonium ylide in CH functionalization.     

Stereoselective synthesis of novel functionalized cyclohexanone derivatives via the condensation of aromatic aldehydes with acetoacetamide and the influence of the ortho-effect and autocondensation

A simple, inexpensive and stereoselective synthesis of novel functionalized cyclohexanone derivatives via the reaction of acetoacetamide with aromatic aldehydes in ethanol at room temperature is described. Additionally, the presence of substituents such as NO₂ and Cl in the ortho-position of the aldehyde aromatic ring resulted in the formation of novel piperidines. The use of Lewis acids such as iron(III) chloride and bismuth(III) nitrate as catalysts led to autocondensation of acetoacetamide and the formation of 2,4-dimethyl-6-oxo-1,6-dihydropyridine-3-carboxamide.     

Synthesis of 2,3,5,6-tetrasubstituted pyridines via selective three-component reactions of aldehyde and two different enaminones

The three-component synthesis of structurally unsymmetrical pyridines with polysubstituted structure has been realized via the catalytic system consisting of CuI and KHSO₄. The employment of two different enaminones is the main factor allowing the successful [3+2+1] construction of the pyridine ring based on the formation of two CC and one CN bonds.     

Silica supported potassium oxide catalyst for dehydration of 2-picolinamide to form 2-cyanopyridine

The dehydration of 2-picolinamide to produce 2-cyanopyridine was investigated thoroughly using silica supported potassium oxide as a heterogeneous catalyst. Both large specific surface area and pore size of SiO_2 (B) contributed to the favorable catalytic performance for the synthesis of 2-CP. In addition, the yield of 2-CP showed the linear relationship with the amounts of medium basicity of the catalysts,demonstrating that medium basic sites were the active sites of silica supported potassium oxide catalysts. The catalysts were further characterized by XRD and FT-IR to clarify the active species. The results indicated the Si—O—K group produced by the reaction of K_2CO_3 with Si—OH was the active species, which was further evidenced by the adjustment of the amount of Si—OH by silylation and hydroxylation procedure.     

Potentiometric and antimicrobial studies on the asymmetric Schiff bases and their binuclear Ni(II) and Fe(III) complexes; synthesis and characterization of the complexes

The protonation constants of two nitro-Schiff bases SB¹, SB² and three asymmetric tetradentate diimines H₂L¹, H₂L² and H₂L³ and the stability constants of their ML type binuclear Ni(II) and Fe(III) complexes have been determined potentiometrically. The asymmetric diimines are (2OH) RCHNC₆H₄CHNR′ (2OH) type compounds [where R = R′ = phenyl for H₂L¹; R = naphthyl, R′ = phenyl for H₂L² and R = R′ = naphthyl for H₂L³]. The effect of tautomeric forms on the acid-base properties of the diimines has been investigated and discussed. In addition, dimeric and binuclear Ni(II) and Fe(III) complexes of the diimines have been synthesized and characterized by physical and spectroscopic techniques. Also, in vitro antimicrobial activities of the diimines and the complexes have been evaluated against three bacteria: Micrococcus luteus (NRLL B-4375), Bacillus cereus (RSKK 863), Escherichia coli (ATCC 11230) and the fungus: Candida albicans (ATCC 10239).     

A synthesis of cephalostatin 1

A synthesis of cephalostatin 1 from hecogenin is described in detail. The gram-scale synthesis of south part features a Baeyer–Villiger oxidation of hecogenin to 16,20-diol, a selective oxidation of C16OH with Dess–Martin periodinane, a Rh(I)-catalyzed C15C16 double bond shift to C14C15 position, and a Hg(OAc)₂-mediated spiroketal formation from cyclic enol ethers with alkenyl side chain at 2-position. Key transformations in the synthesis of north part, also on gram scale, include an abnormal Baeyer–Villiger oxidation of hecogenin to the corresponding dinorcholanic lactone, where a catalytic amount of iodine acts as a traceless and catalytic switch, an umpolung of steroidal 22-aldehyde to forge C22C23 bond with good stereochemical control, a cascade spiroketal-forming process to establish DEF rings in one operation, and a selective oxidation of C3OH. There are also other noteworthy transformations that, although not used in our final route, are valuable and could be applied to other syntheses, including: intra- or intermolecular S_N2′ processes of C14-heteroatom-substituted C15C16 alkenes, an unprecedented rearrangement of β-adduct of D-ring dienes and singlet oxygen, a chelation-controlled methylallylation of C23 aldehyde, and so on.     

Cobalt-catalyzed electrochemical CH/NH functionalization of N-(quinolin-8-yl)benzamide with isocyanides

An efficient synthesis of functionalized iminoisoindolinone derivatives has been achieved via a mild electrochemical oxidative CH/NH functionalization/intramolecular annulations with isocyanides in undivided cell equipped with a nickel cathode. In the presence of earth abundant cobalt catalyst, versatile iminoisoindolinone derivatives obtained in good yields and in a sustainable manner by using electricity as an oxidant in place of stoichiometric amount of silver and copper salts.     

Facile one-pot synthesis of novel highly functionalized dihydro-1H-pyrrole derivatives catalyzed by molecular iodine

An efficient, environmentally benign and molecular iodine promoted protocol was described for cascade synthesis of two kinds of novel dihydro-1H-pyrrole derivatives, 5 and 7. Compounds 5 were prepared via four-component reaction between diethyl acetylenedicarboxylate (DEAD), aromatic amines and phenylglyoxal monohydrate catalyzed by 10 mol% of iodine in ethanol at room temperature. In addition, using same reaction conditions, a three-component reaction between (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), aromatic amines and arylglyoxal monohydrate was performed to access product 7. These transformations apparently proceed through an imine intermediate followed by iodine induced Mannich reaction and subsequent intra-molecular cyclization sequences. The protocol involves the formation of CN, CC and OH bonds leading to the preparation of a hexa substituted five membered ring with two stereo centres. The syntheses avoid the use of traditional column chromatography and recrystallization purification methods and, hence, follow the group-assisted purification (GAP) chemistry process.     

Crystal structure,conformation and vibrational characteristics of diethyl 4,4′-disulfanediylbis(6-methyl-2-phenylpyrimidine-5-carboxylate) – A new pharmaceutical cure

The crystal and molecular structures of diethyl 4,4′-disulfanediylbis(6-methyl-2-phenylpyrimidine-5-carboxylate) have been determined by X-ray diffraction and quantum chemical DFT analysis. The title compound crystallizes in orthorhombic Pbca (D_2h¹⁵) space group, with one molecule in the asymmetric unit. The molecular structure of the studied compound has been determined using the DFT B3LYP/6-311G(2d,2p) approach and compared to that derived from X-ray studies. The IR and Raman spectra have been measured and their wavenumbers have been compared to those calculated for the optimized geometry of the studied compound. The characteristic vibrations of the 4,4′-dithiobispyrimidine N₂C₄SSC₄N₂ skeleton have been identified and on this basis the correlation between the disulfide bridge conformation and vibrational data have been discussed.     

Photoreaction of anthracenyl phosphine oxides: Usual reversible photo- and heat-induced emission switching,and unusual oxidative PC bond cleavage

Anthracenyl(diphenyl)phosphine oxide and dianthracenylphenylphosphine oxide as photoactive compounds have been synthesized. Anthracenyl group of these compounds indicate the multi-functional roles such as an emission component, a photodimerization component, and a leaving group. When the light irradiation was performed under an oxygen atmosphere, photo-oxidative PC bond cleavage to leave the antharacenyl group was observed. Moreover, phosphonyl radical was produced and then PP bond formation to form diphosphane was observed.     

Cobalt(II)–catalyzed C8H alkoxylation of 1-naphthylamine derivatives with alcohols

An efficient protocol for cobalt (II)-catalyzed regioselective aryl C8H bond alkoxylation of 1-naphthylamine derivatives with readily available alcohols has been developed, demonstrating an efficient approach to 8-alkoxy-1-naphthylamine derivatives with good functional group tolerance. Note that the picolinamide moiety as a bidentate directing group may play a key role in this regioselective transformation.     

Transition metal-catalyzed CH functionalization of arylacetic acids for the synthesis of benzothiadiazine 1,1-dioxides

Copper-catalyzed practical route for the synthesis of benzothiadiazine 1,1-dioxides has been developed. The method involves CH functionalization of arylacetic acids to form aromatic aldehydes and their subsequent condensation with 2-aminobenzenesulfonamide. This functional group tolerant approach furnished benzothiadiazine 1,1-dioxide derivatives in good to excellent yields. Broad substrate scope, inexpensive catalyst and high product yields are notable features of this protocol.     

UV-induced catalyst-free intramolecular formal Heck reaction

A catalyst-free intramolecular formal Heck reaction has been developed, affording 9-benzylidene-9H-fluorene derivatives under UV irradiation. This reaction probably proceeds via UV-induced homolytic cleavage of CI bond, addition of the aryl radical to the alkene moiety, single electron oxidation of alkyl radical intermediate into carbocation species, and deprotonation.     

DDQ-promoted C(sp3)H phosphorylation of cycloheptatriene

An efficient and convenient C(sp³)H phosphorylation has been achieved via the DDQ-promoted cross-dehydrogenative coupling between cycloheptatriene and P(O)H compounds at room temperature. This transformation provides a direct synthetic route to the construction of C(sp³)P bonds with good functional group compatibility, leading to the formation of cyclohepta-2,4,6-trien-1-ylphosphonates in up to 99% yield.     

Palladium-catalyzed direct ortho CX bond construction via CH activation of azobenzenes: Synthesis of (E)-1,2-b(2,6-dibromo(chloro)-phenyl)diazene

A palladium-catalyzed direct CX bond formation of azobenzenes with 1,3-dibromo-5,5-dimethylhydantoin or trichloro isocyanuric acid via CH activation has been developed. The reaction could proceed smoothly under an air atmosphere at 110 °C in the presence of Pd(Ph₃P)₄ in DCE and 13 examples of products were obtained.     

An ab initio study of the valence tautomerism of type B mesoionic rings

The MP2 calculated Gibbs free energies of a series of type B mesoionic rings and their acyclic valence tautomers suggest that in the gas phase the relative stability of the mesoionic ring increases with single bond strength (SS > RNNR > OO). Inclusion of aqueous solvation in the calculations further favours the stability of the mesoionic ring by ～10–15 kcal mol^?1. Replacement of CR groups at ring positions by nitrogen atoms results in a significant increase in the relative stability of the mesoionic ring. Calculations of aromatic stabilization energy (ASE), together with the Bird aromaticity index (I₅), suggest that aromaticity decreases with aza substitution and the increase in relative stability is attributable to charge stabilisation by the electronegative nitrogen atoms, which more than compensates for any loss of aromaticity.     

Geometry,stability and aromaticity of β-diketiminate-coordinated alkaline-earth compounds

Alkaline-earth (Ae) metals have attracted a wealth of interdependent research from synthetic chemists. In Ae-catalyzed organometallic reactions, β-diketiminate is a typical ligand used to stabilize Ae catalysts by forming six-membered rings comprising Ae metals. Herein, studies focusing on the configuration of β-diketiminate-coordinated Ae compounds observed that the CC and CN bonds are homogeneous and unchanged. Furthermore, energetic studies observed that the formation of the Ae-incorporated six-membered rings results in enhanced stability of >20 kcal/mol. The nucleus-independent chemical shifts, anisotropy of the induced current density, and molecular orbital analyses demonstrated the non-aromaticity of the β-diketiminate-coordinated Ae compounds. The improved stability of these compounds can be explained by the delocalization of the π electrons derived from the β-diketiminate moiety.