Sustainable Approaches to the Synthesis of Metallophthalocyanines in Solution

This work aims to investigate more sustainable reaction conditions for the synthesis of metallophthalocyanines. Anisole, glycerol and their mixtures have been investigated as reaction media for the tetramerization of phthalonitriles. Acetates of three divalent first-transition metal cations, Co(II), Cu(II) and Zn(II), were used and several bases were tested, depending on the chosen substrates and reaction conditions, with a view to making the whole process more sustainable while ensuring its scalability. Unsubstituted phthalocyanines were synthesized to analyze the behavior of the different metal ions in terms of reactivity in the new reaction media, resulting in a general Cu > Co > Zn trend, while the nonpolar tetra-tert-butyl substitution was investigated to evaluate the synthesis of soluble derivatives in the new conditions. Furthermore, the potassium hydroxide (KOH)-aided statistical synthesis of the unsymmetrical 9(10), 16(17), 23(24)-tri-tert-butyl-2-iodophthalocyaninato zinc(II), starting from 4-tert-butylphthalonitrile and 4-iodophthalonitrile in a glycerol/anisole mixture, proceeded with a satisfactory 26% yield. Our results provide insights into the investigation of new reaction environments and the understanding of their strengths and weaknesses, with a view to further increasing the sustainability of the synthesis of metallomacrocycles with high added value while lowering their production cost.     

Total synthesis of 4-epi-atpenin A5 as a potent nematode complex II inhibitor

It is clear that atpenins and their analogs are useful chemical tools for elucidation of complex II functionality and that they could act as lead compounds for the development of novel helminth complex II-specific inhibitors. Recently, we discovered 4-epi-atpenin A5 as a potent nematode complex II inhibitor during our SAR studies of atpenin A5. This result led us to embark on a concise total synthesis of 4-epi-atpenin A5. In this study, we describe the total synthesis of 4-epi-atpenin A5. Importantly, this was more concise and practical synthesis than our previous total synthesis of atpenin A5.     

Palladium(II)-catalyzed tandem annulation reaction of o-alkynylbenzoates with methyl vinyl ketone for the synthesis of isocoumarins

A palladium(II)-catalyzed highly regioselective tandem reactions of o-alkynylbenzoates with methyl vinyl ketone for the synthesis of isocoumarins was developed. It is a convenient, mild and environmentally benign reaction with moderate to high yield. The reaction is initiated by the Pd(II) species and regenerate the Pd(II) species to complete the catalytic cycle without the necessity of a redox system.     

Imino-ene reaction of N-tosyl arylaldimines with α-methylstyrene: application in the synthesis of important amines

Copper(II) or tin(II) trifluoromethanesulfonate in combination with TMSCl effectively activates a C-H bond for the imino-ene reaction of N-tosylarylaldimines with α-methylstyrene. A wide variety of N-tosylarylaldimines were used to give homoallylamines in good to excellent yields under mild conditions. The imino-ene adduct was converted into a β-amino ketone. The synthesis of a 2,4-substituted pyrrolidine and a piperidine was also achieved from the imino-ene product via a Mitsunobu reaction and a Grubbs cyclization, respectively.     

Divergent synthesis of (+)-tanikolide and its analogues employing stereoselective rhodium(II)-catalyzed reaction

In this study, we described the divergent synthesis of (+)-tanikolide and its analogues, such as (4S)- and (4R)-hydroxytanikolides, and nortanikolide, employing a stereoselective dirhodium(II)-catalyzed reaction to construct the quaternary chiral center of tanokolides. The key steps involve (a) a dirhodium(II)-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement, (b) an N-heterocyclic carbene-catalyzed ring-expansion lactonization of tetrahydrofurfural, or (c) an oxidative cleavage of tetrahydrofuran-5-methanol to γ-lactone using a 2-iodobenzamide catalyst. This route would provide high flexibility for analogue synthesis because the long side chain can be introduced at a later stage in the synthesis.     

A new reagent for the synthesis of [26]hexaphyrin: N-sulfonyl aldimine

The selective synthesis of [26]hexaphyrin(1.1.1.1.1.1) has been achieved by the reaction of meso-substituted tripyrrane and N-sulfonyl aldimine. The protocol is simple and requires only a catalytic amount of copper(II) triflate under mild reaction conditions.     

Platinum(II)-bis-(N-heterocyclic carbene) complexes: synthesis, structure and catalytic activity in the hydrosilylation of alkenes

Chelating biscarbene ligands increase the stability of metal-organic catalyst systems. The catalytic activities of seven structurally different platinum(II)-bis-NHC-complexes in the hydrosilylation of alkenes have been investigated and compared with the catalytic activity of the Karstedt catalyst and of a highly active platinum(0)-NHC-complex. It is shown that a fine-tuning of the catalytic activity of the platinum(II)-bis-NHC-complexes is possible. The synthesis of a platinum(II)-bis-NHC-complex with similar activity, but additional advantages compared to the Karstedt catalyst, is reported. The solid state structure of 1,1-[Bis(3,3′-(4-methoxyphenyl)-1,1′-1H-imidazolium-2,2′-ylidene)methanediyl]platinum(II)-dichloride is presented.     

Reactions of acetylenes with transition metals : VII steric effects in the oligomerization of diarylacetylenes

The synthesis of ortho-substituted diphenylacetylenes and their behaviour toward dichlorobis(benzonitrile)palladium(II) are described. The influence of steric factors on the oligomerization is discussed.     

A higher yielding synthesis of the clinical prodrug ZD2767P using di-protected 4-[N,N-bis(2-hydroxyethyl)amino]phenyl chloroformate

A novel synthesis is described of the prodrug ZD2767P (in Phase I/II clinical trials) that improves the overall yield from 13% to 45%. The method involves the synthesis of 4-[N,N-bis(2-hydroxyethyl)amino]phenyl chloroformate protected as the bis-silyl ether, coupled with di-tert-butyl glutamate. There are clear advantages of this method compared to the literature procedure.     

Synthesis and absolute configuration of (−)-chettaphanin I and (−)-chettaphanin II

An efficient synthesis of chettaphanin I and II has been achieved from ent-halimic acid. The absolute configuration of the natural products was established by nOe experiment and by X-ray analysis of chettaphanin II.     

An efficient method for construction of tetrahydroisoquinoline skeleton via double cyclization process using ortho-vinylbenzaldehydes and amino alcohols: application to the synthesis of (S)-cryptostyline II

Thermal double cyclization reaction using ortho-vinylbenzaldehyde and 3-aminopropanols proceeded smoothly to give isoquinoline derivatives via 6π-azaelectrocyclization pathway. The method was applied to the efficient synthesis of (S)-cryptostyline II.     

Diastereoselective total synthesis of (+)-morusimic acid B, an amino acid from Morus alba

An efficient, flexible and diastereoselective synthesis of the naturally occurring pyrrolidine amino acid, (+)-morusimic acid B, has been accomplished. Starting from chiral, optically active (+)-(3S)-hydroxy butyric acid methyl ester the key steps of our synthesis are diastereoselective α-alkylation of its dianion to introduce the main part of the side chain, Curtius rearrangement of the hydrazide derivative to a 2-oxazolidinone followed by N→π-cyclization with mercury(II) acetate to generate the cis-2,5-disubstituted pyrrolidine ring. The remote C-3 stereocentre is established after chain elongation with the dianion of methyl acetoacetate and asymmetric hydrogenation of the resulting β-oxoester with Noyori's Ru(II)-(R)-BINAP catalyst.     

Conversion of Magnus salt into diamminedichloroplatinum(II) isomers in aqueous solution

The conditions inducing conversion of Magnus salt into diamminedichloroplatinum(II) isomers were studied. Syntheses of cis-diamminedichloroplatinum(II) and trans-diamminedichloroplatinum(II), which are used to prepare potassium or ammonium amminetrichloroplatinate(II), are described. The identity and structure of diamminedichloroplatinum(II) isomers were verified by elemental analysis, X-ray powder diffraction, and IR and UV spectroscopy. A workflow for preparing potassium or ammonium amminetrichloroplatinate(II) from diamminedichloroplatinum(II) isomers was developed. This workflow appreciably increases the product yield due to the return of unused Magnus salt to the main synthesis flow.     

New Pd-NHC-complexes for the Mizoroki-Heck reaction

The synthesis and structural characterization of novel chelating N-aryl substituted palladium(II)-biscarbene-complexes is reported: 1,1′-bis(4-bromophenyl)-3,3′-methylene-diimidazoline-2,2′-diylidene-palladium(II)-dibromide, 1,1′-bis(4-methoxyphenyl)-3,3′-methylene-diimidazoline-2,2′-diylidene-palladium(II)-dibromide and 1,1′-bis(4-n-butoxyphenyl)-3,3′-methylenediimidazoline-2,2′-diylidene-palladium(II)-dibromide have been synthesized in good yields. The catalytic activity of these 1,1′-aryl-3,3′-methylenediimidazoline-2,2′-diylidene-palladium(II)-dihalogenide complexes was tested for the Mizoroki-Heck reaction in comparison to 1,1′-(bis)methyl-3,3′-methylenediimidazoline-2,2′-diylidene-palladium(II)-dihalogenide complexes and to 1,1′-bis(phenyl)-3,3′-methylene-diimidazoline-2,2′-diylidene-palladium(II)-dibromide. The activity of the aryl substituted catalysts is significantly higher compared to the methyl substituted NHC complexes. They also allow the coupling of arylchlorides with olefins.     

Insect pheromones and their analogs. VII. Synthesis of the sex pheromone of the fruit flyCeratitis capitata

A new and simple route to the synthesis of non-6E-en-l-ol (I) — the pheromone of the fruit flyCeratitis capitata Wiedemann — has been proposed on the basis of the readily available co-oligomer of butadiene and phenol, 1-phenoxyocta-2E, 7-diene (II).     

N-Acetyl-5-arylidenetetramic acids: synthesis,X-ray structure elucidation and application to the preparation of zinc(II) and copper(II) complexes

A new route to N-acetyl-3-acyl-5-arylidenetetramic acids was developed and applied to the synthesis of a small library of compounds with diversity at carbon 3 of the heterocyclic ring. The 3-acetyl derivative was used as ligand for complexation with zinc(II) and copper(II) acetates. Both the ligand and the zinc complex were studied by X-ray single crystal structure analysis, the zinc complex forms ribbons by H-bonding from the ethanol to a neighbouring molecule.     

PdCl2/CuCl2-catalysed chlorocyclisation of sugar-derived aminoalkenitols in the synthesis of new iminohexitols

The total synthesis of two novel l-ido and l-altro configured 6-chloro-1,5,6-trideoxyiminohexitols featuring a highly diastereoselective Pd(II)/CuCl₂-catalysed chlorocyclisation of sugar-derived aminoalkenitols has been accomplished. The requisite substrates were, in turn, prepared from chiral pool materials starting from the cheap and commercially available methyl-α-d-gluco- and methyl-α-d-galactopyranoside.     

Synthese eines 3-phenylisochromans

We describe an independent synthesis of the 3-phenylisochromane II via the desoxybenzoin XIV. In connection with this synthesis we publish simple methods for preparing highly substituted desoxybenzoins and 3-phenyl-α-naphthols.     

N-Hydroxyphthalimide in combination with Cu(II), Co(II) or Mn(II) salts as catalytic systems for the oxidation of isopropyl-aromatic hydrocarbons with oxygen

Catalytic systems consisting of N-hydroxyphthalimide in combination with copper(II), cobalt(II) and manganese(II) acetylacetonate, acetate or chloride were applied to the oxidation of cumene with oxygen. The use of these catalytic systems decreases cumyl hydroperoxide selectivity as a result of the decomposition reaction of hydroperoxide to 2-phenyl-2-propanol and acetophenone. It has been demonstrated that the use of N-hydroxyphthalimide in combination with copper salts at 60 °C results in high alcohol content whereas ketone is the major product at 90 °C. The results can be used to develop a method for alcohol or ketone synthesis from other isopropyl-aromatic hydrocarbons.     

Copper catalyzed arylation with boronic acids for the synthesis of N-aryl purine nucleosides

The synthesis of a series of N¹-aryl inosine and guanosine derivatives is described. The procedure for chemoselective N¹-arylation involves the mild oxidative copper(II) mediated coupling with boronic acids. This approach provides access to substituted N¹-aryl purines with interesting structural characteristics and novel scaffolds for drug discovery.