Catalyst-free aminobromination of alkenes with N-methyl-p-toluenesulfonamide as nitrogen resource

A catalyst-free electrophilic aminobromination system was described with N-methyl-p-toluenesulfonamide (p-TsNHCH₃) and N-bromosuccinimide (NBS) as nitrogen and bromine resources. The reaction can give vicinal haloamines in good yields, excellent regioselectivities, and stereoselectivities under convenient and mild condition. The existence of N-methyl group in the nitrogen resource was found to play an important role in the formation of vicinal haloamine product.     

C-Galactosylceramide diastereomers via Sharpless asymmetric epoxidation chemistry

C-Glycoside analogs of α-galactosylceramide (KRN7000) were synthesized in 19 linear steps with Sharpless asymmetric epoxidation as a key reaction. Opening of a hydroxy epoxide with sodium azide provided an anti vicinal azido diol with inversion of configuration at the azide-bearing carbon while opening with Ti(O-i-Pr)₂(N₃)₂ gave syn vicinal azido diol with retention. The latter, unusual outcome could be rationalized either by invoking Ti-catalyzed intramolecular double S_N2 inversion or by epoxide opening/intramolecular delivery of azide from the Ti complex.     

Selectivities in the reaction of vicinal diimines and acyl chlorides

The reaction of vicinal diimines and acyl chlorides in the presence of triethylamine produces 3-imino-β-lactams and/or bis-β-lactams chemo-, regio-, and stereoselectively, which are important intermediates in pharmaceutical and organic synthesis. The selectivities in the reaction have been investigated. The results indicate that all diimines react with various ketenes generated from acyl chlorides in the presence of triethylamine to give rise to cis-4-imino-β-lactams (mono-cis-β-lactams) diastereoselectively due to the electron-withdrawing property of the imino group in the vicinal diimines. Bis-β-lactams were obtained from diimines via the mono-cis-β-lactams as intermediates. Only ketenes with strong electron-donating substituents can react with the mono-cis-β-lactams to yield bis-β-lactams, affording a pair of C2-symmetric cis-bis-β-lactams with symmetric diimines, two or four pairs of diastereomeric bis-β-lactams with ketoaldehyde-derived unsymmetric diimines depending on the steric hindrance of their N-substituents. The current investigation provides very important information for the selective preparation of mono- and bis-β-lactams from vicinal diimines.     

Theoretical studies on selectivities in the Staudinger reaction of vicinal diimines and ketenes

The selectivities,including peri-,regio-,and diastereoselectivities,in the Staudinger reaction involving vicinal diimines and ketenes were investigated theoretically via the density functional theory(DFT) calculation.The results indicate that vicinal diimines prefer stepwise [2+2] cycloaddition rather than [2+4] cycloaddition to generate cis-4-imino-β-lactams.The diimines attack the less sterically hindered exo-side of ketenes to generate zwitterionic intermediates,which directly undergo a conrotatory ring closure to produce cis-4-imino-β-lactams whatever diimines with less or more bulky N-substituents.For unsymmetric vicinal ketoaldehyde-derived diimines,their ketimines attack the exo-side of ketenes and undergo a conrotatory ring closure to produce cis-4-aldimino-β-lactams due to less steric effect.The current theoretical studies provide very important information for in-depth understanding of the selective formation of mono-cis-β-lactams from vicinal diimines and ketenes.     

Synthesis of sulfur-containing vicinal aminoalcohols on the basis of N-(oxiran-2-ylmethyl)amines

The reaction of (methanediyldibenzene-4,1-diyl)dimethanethiol, (oxydibenzene-4,1-diyl)dimethanethiol, biphenyl-4,4′-diyldimethanethiol with 1-(oxiran-2-ylmethyl)piperidine and N-(oxiran-2-ylmethyl)-N-ethylaniline afforded the corresponding sulfur-containing vicinal aminoalcohols resulting from the opening of the oxirane ring in keeping with Krasusky rule.     

The combination of TsNBr2/TsNH2 as the nitrogen/halo source for the aminobromination of β-methyl-β-nitrostyrenes catalyzed by Mn(OAc)2

The combination of N,N-dibromo-p-tolunesulfonamide (4-TsNBr₂) and TsNH₂ was found to be an efficient halogen/nitrogen source for the aminohalogenation of β-methyl-β-nitrostyrenes with manganese (II) acetate as the catalyst in the presence of 4 Å molecular sieves. The reaction results in vicinal bromoamino nitroalkanes with the opposite regioselectivity comparing with those reported, which was also confirmed by X-ray structural analysis.     

Palladium-catalyzed construction of amino acid derivatives possessing vicinal chiral quaternary and tertiary carbon centers at the α and β positions

The palladium catalyzed regio- and diastereo-selective allylic alkylation of (R)-2-acetoxy-4-aryl-3-butene with N-(diphenylmethylidene)glycinate and N-(diphenylmethylidene)alaninate occurred. The stereochemistry was controlled by the use of o-(diphenylphosphino)carboxylic acid, and produced new amino acid derivatives possessing vicinal chiral quaternary and tertiary carbon centers at the α and β positions.     

An efficient chemoenzymatic method to prepare optically active primary-tertiary trans-cycloalkane-1,2-diamines

Optically active trans-N-Boc-cyclopentane- and cyclohexane-1,2-diamines (7) were prepared by a chemoenzymatic method from the corresponding (±)-trans-N,N-diallylcycloalkane-1,2-diamine. These mono-carbamates 7 (ee=99%) were used as the starting materials in the syntheses of different vicinal primary-tertiary diamines. Thus, by means of a simple three-step sequence involving a reductive-amination of an aromatic aldehyde with 7, N-methylation and finally, cleavage of the Boc group, several trans-N-(arylmethyl)-N-methylcyclopentane- and cyclohexane-1,2-diamines were obtained in high yields.     

Organocatalyzed regio- and stereoselective diamination of functionalized alkenes

The first organocatalyzed diamination reaction of alkenes with N,N-dichlorotoluenesulfonamide (TsNCl₂) and acetonitrile as nitrogen sources was reported. The catalytic diamination reaction was convenient to carry out, resulting in imidazoline products with good yields and excellent regio- and stereoselectivities. Several other organic molecules were also tried as catalyst for this reaction and good results were achieved. A new one-pot synthesis of vicinal diamines via the current PPh₃-catalyzed diamination and the hydrolysis of resulting imidazoline products with SnCl₄ as promoter was also established.     

Synthesis of chiral vicinal C2 symmetric and unsymmetric bis(sulfonamide) ligands based on trans-1,2-cyclohexanediamine by aminolysis of N-tosylaziridines

The ring opening of N-tosylaziridines with aliphatic amines can be efficiently catalyzed by lithium perchlorate to provide derivatives of the trans-1,2-diamine in high yields. The reaction was used in desymmetrization of several cyclic N-tosylaziridines using chiral amines. Using this strategy, an efficient synthesis of chiral vicinal C₂ symmetric bis(sulfonamide) and unsymmetrical bis(sulfonamide) ligands based on trans-1,2-cyclohexanediamine was developed.     

BiI3 mediated difunctionalization of α-methylstyrenes,including azidohydroxylation and azidoiodination

BiI₃ mediated vicinal azidohydroxylation of α-methylstyrenes 1 with NaN₃ in wet DMF affords β-azidoalcohols 4 in good yields. In dry DMF, β-azidoiodides 6 are also obtained by BiI₃ mediated vicinal azidoiodination of α-methylstyrenes 1 with NaN₃. This present protocol provides the bond formations of carbon-azido/carbon-hydroxy (N₃─CC─OH) bond and carbon-azido/carbon-iodo (N₃─CC─I) under water-controlled conditions.     

Tunable dendritic ligands of chiral 1,2-diamine and their application in asymmetric transfer hydrogenation

Tunable dendritic N-mono-sulfonyl ligands have been designed and synthesized via direct N-mono-sulfonylization of the chiral dendritic vicinal diamines and their ruthenium complexes demonstrated high catalytic and recyclable activities with comparable enantioselectivities to Noyori–Ikariya’s TsDPEN-Ru in the asymmetric transfer hydrogenation of an extended range of substrates, such as ketones, keto esters, and olefins.     

Synthesis of hindered chiral guanidine bases starting from (S)-(N,N-dialkyl-aminomethyl)pyrrolidines and BrCN

An efficient method for the preparation of hindered chiral guanidines using cyanogen bromide is described. The reaction between BrCN and vicinal diamines derived from (S)-2-(N,N-dialkyl-aminomethyl)-pyrrolidines provides chiral substituted cyanamides. The cyanamide derivatives reacted with secondary amines in hexafluoroisopropanol at reflux to form chiral hindered guanidines, which were isolated in good to excellent yields (70–96%). The chiral guanidines were prepared in an effort to design sophisticated chiral guanidine catalysts for asymmetric synthesis.     

Chemoenzymatic preparation of optically active trans- and cis-cyclohex-4-ene-1,2-diamine and trans-6-aminocyclohex-3-enol derivatives

Lipase from Burkholderia cepacia (PSL-C) effectively catalyzed the kinetic resolution of both racemic trans-N,N-diallylcyclohex-4-ene-1,2-diamine (±)-6 and its precursor trans-6-(diallylamino)cyclohex-3-enol (±)-5. The resulting optically active vicinal diamine and β-amino alcohol were converted into a precursor of oseltamivir and a cis-cyclohex-4-ene-1,2-diamine derivative, respectively.     

Synthesis of 4-aminopyrazolo[3,4-d]pyrimidine derivatives from 5-acetyl-6-amino-4-methylsulfanyl- or 5-acetyl-6-amino-4-methylsulfonylpyrimidines

Diacetyl ketene N,S-acetal was used for the synthesis of 5-acetyl-6-amino-4-methylsulfanylpyrimidines substituted at the exocyclic nitrogen atom, which were further oxidized with m-chloroperbenzoic acid to the corresponding methylsulfonylpyrimidines. Reactions of hydrazines with these pyrimidines containing vicinal Ac and MeS (or MeSO₂) groups were used for the preparation of new 4-aminopyrazolo[3,4-d]pyrimidine derivatives.     

Asymmetrical nonbridgehead nitrogen—30 geminal systems—21: The influence of vicinal n — σ* interaction on the pyramidal stability of tricoordinated nitrogen atom in the geminal system

The vicinal n - σ^* interaction stabilizes the pyramidal state of the nitrogen geminal system

where X and Y are electronegative substituents with high-lying levels of nonbonding n orbitals. A approximate value for the energy of n - σ^* stabilization of pyramidal state in $\text{N}$,$\text{N}$-dialkoxyamines, equal to ～5.7 kcal/mol, has been found by comparing the average experimental value of the inversion barrier for these compounds with the one calculated according to the additive scheme. The influence of the vicinal n - σ^* interaction on the structural peculiarities of $\text{N}$-alkoxyisoxazolidines manifests itself in the conformations with the greatest overlapping of n and σ^* orbitals being predominantly populated and in a change in NO bond lengths and valence angles. The combination of a ligand having the highest-lying level of n orbital with a ligand, which forms the σ bond with a N atom, having the lowest-lying antibonding level results in the dissociation of a nitrogen geminal system into an ionic planar form of the

type. From this is inferred the dual nature of the influence exerted by the vicinal n - σ^* interaction upon the inversion barrier of the

geminal system.     

Preparation of new gem-difluoro heterocyclic-fused 1,2,3-triazole derivatives

Starting from easily accessible gem-difluoropropargylic derivatives a cascade nucleophilic substitution by N₃^–, followed by an intramolecular 1,3 dipolar cycloaddition, afforded in fair to good yields new 1,2,3-triazoles fused to pyrrolidines or piperidines. These molecules, with a gem-difluoro group vicinal to the triazoles, are fluorinated analogues of bioactive heterocycles. In parallel, a few open chain analogues have been prepared in order to evaluate the possible role of the bicyclic core on the biological properties of such molecules.     

Stereoselective allylation of α-hydroxy aldimines and its application to the formal synthesis of (−)-β-conhydrine

Stereoselective allylation of N-p-methoxyphenyl (PMP)-substituted α-hydroxy aldimines is described. Several Lewis acids (BF₃·OEt₂, SnCl₄, TiCl₄, ZnCl₂, and MgBr₂·OEt₂) were employed to mediate the allylation reactions. The addition of the allyl group generates a new stereocenter and affords the syn vicinal amino alcohol. Formal synthesis of (?)-β-conhydrine (1) was accomplished via syn-selective allyl addition to N-PMP-substituted α-hydroxy aldimine.     

Facile synthesis of vicinal diamines via oxidation of N-phenyltetrahydroisoquinolines with DDQ

The oxidation of N-phenyltetrahydroisoquinolines occurs rapidly with DDQ. Under ambient conditions and in the presence of nitromethane, the corresponding β-nitroamine derivatives are isolated in good to excellent yields. Variation in the electronic nature of the isoquinoline and the N-phenyl substituent showed that a broad range of substituents are tolerated, with electronic communication between the isoquinoline aromatic ring and the C1 carbon being stronger than with the N-aryl ring. Reduction of the β-nitroamines to the corresponding novel chiral vicinal diamines are straightforward. Examination of the reaction by ¹H NMR spectroscopy suggested that the reaction proceeds via an iminium ion, which then reacts with nitromethane upon work-up. This information was used to shorten the required reaction time.     

Acceleration of bromide mediated benzoylperoxide oxidations of secondary alcohols in aqueous organic solvents

The efficiency of the bromide mediated benzoylperoxide oxidation of 2° alcohols to ketones was greatly improved by the addition of water. The aqueous oxidation protocol allows also the direct use of off-the-shelf benzoylperoxide reagent without an otherwise necessary and potentially dangerous drying procedure. The oxidation of cyclopentanol, cyclohexanol, 1-phenyl-ethanol and three menthol isomers occurred in good to excellent yields. The oxidation reaction tolerated N,N-dimethylacetamide (DMA) as the solvent, which resulted in a slightly lower oxidation rate than acetonitrile. Chemoselective oxidation of vicinal diols to α-hydroxy ketones did not succeed under the aqueous organic conditions employed as over-oxidation and bromination side-reactions were observed. The impact of water content, solvent, oxidant source and type of alcohol substrates employed was investigated.