Halogenation of N-substituted p-quinone imines and p-quinone oxime esters: IV. Chlorination and bromination of N-arylsulfonyl-2(3)-methyl(2-chloro)-1,4-benzoquinone monoimines

The addition of halogens to N-arylsulfonyl-1,4-benzoquinone imines, which exist in a solution as Z and E isomers, is controlled by the steric factor. Z-E Isomerization strongly affects the stability of cyclohexene structures formed by halogenation of 1,4-benzoquinone imines. The halogenation of N-arylsulfonyl-1,4-benzoquinone imines was found to be accompanied by prototropic rearrangement.     

Water-soluble 2-aminomethylidene-1,3-dicarbonyl compounds as new chalcogenide colloidal stabilizers

Reactions of 2-ethoxymethylidene derivatives of 1,3-dicarbonyl compounds with N,N-dimethylethane-1,2-diamine gave a number of 2-[(2-dimethylaminoethyl)amino]methylidene-1,3-dicarbonyl compounds which were subjected to regioselective quaternization at the tertiary nitrogen atom with methyl iodide. The resulting quaternary ammonium salts inhibited aggregation of cadmium and zinc sulfide sols in aqueous medium.     

Halogenation of N-substituted p-quinone monoimines and p-quinone monooxime ethers: XIV. Halogenation of N-[arylsulfonylimino(phenyl)methyl]-2,5-dialkyl-1,4-benzoquinone monoimines and their reduction products

Despite steric hindrances created by the bulky substituent on the nitrogen atom, halogenation of 2,5-dialkyl-N-[arylsulfonylimino(phenyl)methyl]-1,4-benzoquinone monoimines fairly readily gives their derivatives having two halogen atoms in the quinoid ring.     

Halogenation of N-substituted p-quinone monoimines and p-quinone monooxime esrers: XI. Synthesis and halogenation of 4-[aryl(alkyl)aminocarbonyl-oxyimino]cyclohexa-2,5-dien-1-ones

4-[Aryl(alkyl)aminocarbonyloxyimino]cyclohexa-2,5-dien-1-ones were synthesized by treatment of various substituted p-quinone monooximes with aryl isocyanates. The selectivity in the halogenation of the obtained p-quinone monooxime esters depended on the substrate structure and was either completely (syn addition) or partly regioselective (syn or anti addition). In all cases, the effect of steric factor was crucial, and the reaction was accompanied by halogenation of the aryl fragment.     

Amino acids as selective sulfonamide acylating agents

Acylation of antimalarial and bacteriostatic sulfonamides with N-protected amino acids and peptides was carried out using standard peptide coupling methods. These acylation reactions are regioselective for the N⁴ nitrogen atom of diazine-containing sulfonamides. In contrast, only N¹ coupling was found for sulfisoxazole, an isoxazole-based sulfonamide. Computational studies suggest that a combination of geometrical, thermodynamic and electronic factors are responsible for the different reactivities reported.     

Halogenation of N-substituted para-quinone monoimine and para-quinone monooxime esters: VI. Regular trends in chlorination and bromination of N-arylsulfonyl-1,4-benzoquinone monoimines alkyl-substituted in the quinoid ring

Reactions of halogens with N-arylsulfonyl-1,4-benzoquinone monoimines occur with the formation of a halogenonium ion that either transforms into a carbocation where the first halogen atom adds to the carbon in the ortho-position relative to the carbonyl carbon, or the halogenonium ion adds directly the second halogen atom.     

Activated sterically strained C=N bond in N-substituted p-quinone mono- and diimines: XIII. Reactions of N-alkyl(aryl, trifluoromethyl)sulfonyl-, N-arylsulfinyl- and N-arylsulfanyl-1,4-benzoquinone monoimines with alcohols

Steric strains arising between the substituent atoms at nitrogen (S, SO, or SO₂) and the methyl group located in positions 3 or 5 of the quinoid ring of 3,5-dimethyl-substituted quinone monoimines lead to the increased angle C=N-S. As a result in these quinone monoimines the reactions of 1,2-addition become thermodynamically possible since the formation of quinolide structures with the sp³-hybridized carbon atom removes the steric strain.     

Asymmetric synthesis of α- and β-amino acids by diastereoselective addition of triorganozincates to N-(tert-butanesulfinyl)imines

The diastereoselective addition of triorganozincates to (R)-N-(tert-butanesulfinyl)imines has been used as a key step to achieve the synthesis of highly enantiomerically enriched N-protected α- and β-amino acids. Desulfinylation of the addition products followed by benzoylation of the nitrogen atom of the obtained primary amines and oxidation of one of the substituents on the carbon atom connected to the nitrogen complete the sequence. Using the same configuration in the sulfinyl chiral auxiliary, α-amino acids with the (R) or the (S) configuration can be prepared by choosing the proper combination of imine and organozincate. α,α-Disubstituted α-amino esters with high enantiomeric purity can also be prepared when α-imino esters are the starting substrates.     

Application of the addition of triorganozincates to N-(tert-butanesulfinyl)imines to the enantioselective synthesis of α-amino acids

Highly enantiomerically enriched N-protected α-amino acids can be easily prepared from optically pure N-(tert-butanesulfinyl)imines by a four-step sequence involving: diastereoselective addition of a triorganozincate to the imine, removal of the sulfinyl group, benzoylation of the nitrogen atom of the obtained primary amine and oxidation of one of the substituents on the carbon atom α to the nitrogen. Using the same configuration in the sulfinyl chiral auxiliary, amino acids with the (R) or the (S) configuration can be prepared by choosing the proper combination of imine and organozincate. α,α-Disubstituted α-amino esters with high optical purity can also be prepared by the diastereoselective addition of trialkylzincates to α-imino esters.     

Diastereoselective 1,3-dipolar cycloaddition of C,N-diaryl- and C-amido-N-arylnitrones to arylpropenones

C,N-diarylnitrones and C-amido-N-arylnitrones add diastereoselectively to the substituted arylpropenones to give the substituted isoxazolidine possessing 3RS,4SR,5SR configuration. Replacement of the aryl groups either in the position 3 of chalcone or at the nitrogen atom of nitrone by the methyl group decreased the rate of cycloaddition.     

Development of two diastereoselective routes towards trans-4-aminomethyl-piperidin-3-ol building blocks

Two diastereoselective, scaleable routes towards trans-3,4-disubstituted piperidines with a 4-hydroxymethyl-3-hydroxy or 4-aminomethyl-3-hydroxy substitution pattern are being described. In the first route, the 3,4-trans configuration was introduced regio- and diastereoselectively via a hydroboration/oxidation sequence starting from 4-hydroxymethylpyridine. In the second route, regioselective epoxide ring opening of N-benzyl-3,4-epoxy-piperidine was achieved with LiCN, in situ generated from acetocyanohydrin and LiNH₂. The regioselectivity of both the hydroboration and the epoxide ring opening was positively influenced by the presence of the basic piperidine nitrogen. Both routes have been optimized to be performed at large scale.     

Obtention de complexes du platine(II) du type [PtCl2(amine)L] par rupture des dimeres pontes [Pt2Cl4(amine)2]

Opening of chlorine-bridged amine dimers of platinum(II) by various ligands L yields quantitatively complexes of general formula [PtCl₂(amine)L] with a cis configuration in most cases. Cis olefinic complexes may be easily obtained by this method, together with compounds having L as a weak ligand. For the reactions of two-sites ligandsd (nitrogen—olefin), the determining factor seems to be correlated to the nucleophilicity of the binding site; platinum always coordinates at the nitrogen atom of the nitrogen unsaturated ligands which have been studied.     

Diphenyltin(IV) complexes of the 2-quinolinecarboxaldehyde Schiff bases of S-methyl- and S-benzyldithiocarbazate (Hqaldsme and Hqaldsbz): X-ray crystal structures of Hqaldsme and two conformers of its diphenyltin(IV) complex

New organometallic tin(IV) complexes of the empirical formula Sn(NNS)Ph₂Cl (NNS = anionic forms of the 2-quinolinecarboxaldehyde Schiff bases of S-methyl- and S-benzyldithiocarbazate) have been prepared and characterized by IR, electronic, ¹H NMR and ES mass spectroscopic techniques. The molecular structures of the 2-quinolinecarboxaldehyde Schiff base of S-methyldithiocarbazate (Hqaldsme) and its diphenyltin(IV) complex, Sn(qaldsme)Ph₂Cl, have been determined by X-ray diffraction. In the solid state, the ligand remains as the thione tautomer in which the dithiocarbazate chain adopts an E,E configuration and is almost coplanar with the quinoline ring. The Sn(qaldsme)Ph₂Cl complex crystallizes in two distinctly different conformationally isomeric forms, each having the same space group but different lattice parameters. X-ray analysis shows that in each polymorph, the tin atom adopts a distorted octahedral geometry with the Schiff base coordinated to it as a uninegatively charged tridentate chelating agent via the quinoline nitrogen atom, the azomethine nitrogen atom and the thiolate sulfur atom. The two phenyl groups occupy axial positions and the chloride ligand occupies the sixth coordination position of the tin atom. The deprotonated ligand adopts an E,E,Z configuration in the complex.     

Experimental and theoretical investigations for the regio and stereoselective transformation of trans 1,2,3-trisubstituted aziridines into trans oxazolidin-2-ones

The regio and stereoselective transformation of trans 1,2,3-trisubstituted aziridines into trans oxazolidin-2-ones takes place in good yield. However, the cis configuration at C2 and C3 in monocyclic aziridines is a limiting factor for this transformation. Ab initio calculations show that while the ring-opening process assisted by iodide is regioselective, the subsequent ring-closure is responsible for the retention of the configuration at the trans oxazolidin-2-one. The larger energy found for the ring-closure process for the cis aziridines accounts for the non-formation of the cis oxazolidin-2-ones.     

Solid state conformations of α,β-unsaturated hydroxamates derived from the ‘chiral Weinreb amide’ auxiliary (S)-N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine

α,β-Unsaturated hydroxamates derived from the ‘chiral Weinreb amide’ auxiliary (S)-N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxylamine consistently adopt a defined conformation and undergo highly diastereoselective conjugate addition reactions with lithium amide reagents. The configuration of the N-1-(1′-naphthyl)ethyl group dictates the position of the O-tert-butyl group and also the configuration adopted by the pyramidal nitrogen atom via a ‘chiral relay’ effect. Conjugate addition of lithium amide reagents to these substrates proceeds on the face opposite to both the O-tert-butyl group and nitrogen lone-pair with high levels of diastereoselectivity.     

Sodium halides as the source of electrophilic halogens in green synthesis of 3-halo- and 3,n-dihalobenzo[b]thiophenes

A convenient methodology for the synthesis of mono- and di-halogenated benzo[b]thiophenes is described herein, which utilizes copper(II) sulfate pentahydrate and various sodium halides in the presence of substituted 2-alkynylthioanisoles. The proposed method is facile, uses ethanol as a green solvent, and results in uniquely substituted benzo[b]thiophene structures with isolated yields up to 96%. The most useful component of this methodology is the selective introduction of bromine atoms at every available position (2–7) around the benzo[b]thiophene ring, while keeping position 3 occupied by a specific halogen atom such as Cl, Br or I. Aromatic halogens are useful reactive handles; therefore, the selective introduction of halogens at specific positions would be valuable in the targeted synthesis of bioactive molecules and complex organic materials via metal-catalyzed cross coupling reactions. This work is a novel approach towards the synthesis of dihalo substituted benzo[b]thiophene core structures, which provides a superior alternative to the current methods discussed herein.     

Double reductive cyclization: a facile synthesis of the indoloquinoline alkaloid cryptotackieine

A new synthesis of the indoloquinoline alkaloid cryptotackieine, isolated from Cryptolepis sanguinolenta, is described which involves a Perkin reaction, a tandem double reduction-double cyclization reaction followed by regioselective methylation at the quinoline nitrogen.     

Stereocontrolled synthesis of 3-amino-2-hydroxyalkyl diphenylphosphine oxides mediated by chiral azetidinium salts and epoxyamines

The stereocontrolled synthesis of amino hydroxyalkyl diphenylphosphine oxides has been achieved starting from (2S,3S)-N,N-dibenzyl-3-hydroxy-2-methylazetidinium bromide or (1R),[1′(S)-(dibenzylamino)ethyl]oxirane. The regioselective ring opening of both heterocyclic systems at the less substituted carbon atom with phosphorus nucleophiles proceeded with full stereochemical integrity.     

Experimental and computational study of intermolecular migration of N,N-dimethylcarbamoyl group from N(7) to N(1) on a 7-azaindoline derivative

N,N-Dimethylcarbamoylation of the anilinic nitrogen atom N(1) on the spiro 7-azaindoline consists of two steps. The first step is N,N-dimethylcarbamoylation of the pyridyl nitrogen atom N(7), leading to the formation of an isolable intermediate. The second step is intermolecular migration of the N,N-dimethylcarbamoyl group from the pyridyl nitrogen atom N(7) to the anilinic nitrogen atom N(1). We accomplished optimization of the reaction conditions based on the revealed reaction mechanism and a large scale synthesis of compound 3 in quantitative yield.     

Exploratory studies towards a total synthesis of the unusual bridged tetracyclic Lycopodium alkaloid lycopladine H

A strategy for a total synthesis of the structurally novel Lycopodium alkaloid lycopladine H has been investigated. Key steps that have been tested include: 1. a regioselective Diels-Alder cycloaddition of nitroethylene with an o-quinone ketal to produce the bicyclo[2.2.2]octane moiety of the alkaloid; 2. a stereoselective Henry reaction to generate the requisite functionality and configuration at C-5; 3. a stereoselective catalytic hydrogenation of a trisubstituted alkene to set the C-15 methyl configuration.