Vicinal Diamines Research Articles

Efficient Synthesis of a Peculiar Vicinal Diamine Semiochemical from Streptomyces natalensis

The pimaricin-inducing (PI) factor, produced by Streptomyces natalensis is a proposed pheromone with a peculiar vicinal diamine structure. The first synthesis of this molecule is reported. It features oxidative dimerization of an aci-nitro anion derived from tris(hydroxymethyl)nitromethane and disproportionation catalyst-facilitated hydrogenation of the resulting vicinal tertiary dinitro compound. As the synthesis requires only four steps with no chromatographic separations, it provides a convenient route to prepare PI factor for biological studies and industrial applications.

Water enables transimination between hindered ketimines and β-aminoalcohols and selective protection of a vicinal diamine backbone

Water mediates synthesis of novel hindered Schiff bases via transmination protocol. The feature of the procedure is that it allows both tuning of steric and electronic factors of the substituents and mono-imination of vicinal diamines, which potentially facilitates one-pot approach to unsymmetrical metal ligands.

Chiral Primary−Tertiary Diamine−Brønsted Acid Salt Catalyzed Syn-Selective Cross-Aldol Reaction of Aldehydes

Highly syn-selective cross-aldol reaction of aldehydes has remained a challenging subject in the field of aminocatalysis. To achieve this end, chiral primary amines have been explored and the primary-tertiary diamine-Brønsted acid salts are found to promote the cross-aldol reactions of aldehydes with high activity and syn selectivity. Among various vicinal diamines screened, l-phenylalanine derived 2a/TfOH conjugate is identified as the optimal catalyst, showing good catalytic activity (up to 97% yield) and high syn selectivities (syn/anti up to 24:1, 87% ee). The current catalysis works selectively with small aliphatic aldehydes donors such as propionaldehyde and isobutyraldehyde, but not with aliphatic aldehydes bearing larger beta-substitute (>Me). In addition, the use of 2a/TfOH conjugate has also enabled the first syn-selective cross-aldol reactions of glycoaldehyde donors.

Organocatalyzed regio- and stereoselective diamination of functionalized alkenes

The first organocatalyzed diamination reaction of alkenes with N, N-dichlorotoluenesulfonamide (TsNCl 2) 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 PPh 3-catalyzed diamination and the hydrolysis of resulting imidazoline products with SnCl 4 as promoter was also established.

N,N′-Dioxide−Cu(OTf)2 Complex Catalyzed Highly Enantioselective Amination Reaction of N-Acetyl Enamide

The N,N'-dioxide-Cu(OTf)(2) complexes were applied in the asymmetric amination reaction of N-acetyl enamides with dialkyl azodicarboxylate, giving the corresponding products in good yields with high enantioselectivities (up to 91% ee). Precursors of vicinal diamine were readily obtained with excellent diastereoselectivities (>95:5) by NaBH(4) reduction.

Reactivity of the Nickel(0)−CO2−Imine System: New Pathway to Vicinal Diamines

Nickela-2-oxazolidinones, formed by oxidative coupling of imines and CO2 with Ni0, react with LiCl under mild conditions (4 °C, 1 atm) to afford vicinal diamines in up to 89% yield. The reaction is the first organometallic example of reductive imine coupling requiring CO2. In this system, CO2 is participatory and is not incorporated in the reaction products. These results represent an important addition to our understanding of the reactivity of metallacycles derived from CO2 and unsaturated compounds.

I2-Catalyzed Oxidative Condensation of Aldoses with Diamines: Synthesis of Aldo-Naphthimidazoles for Carbohydrate Analysis

A novel method for the conversion of unprotected and unmodified aldoses to aldo-imidazoles has been developed. Using iodine as a catalyst in acetic acid solution, a series of mono- and oligosaccharides, including those containing carboxyl and acetamido groups, undergo an oxidative condensation reaction with aromatic vicinal diamines at room temperature to give the corresponding aldo-imidazole products in high yields. No cleavage of the glycosidic bond occurs under the mild reaction conditions. The compositional analysis of saccharides is commonly realized by capillary electropheresis of the corresponding aldo-imidazole derivatives, which are easily synthesized by the reported iodine-promoted oxidative condensation. In addition, a series of aldo-imidazoles were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI–TOF MS) to analyze molecular weight and ion intensity. The diamine-labeled saccharides showed enhanced signals in MALDI–TOF MS. The combined use of aldo-imidazole derivatization and mass spectrometric analysis thus provides a rapid method for identification of saccharides, even when less than 1 pmol of saccharide is present in the sample. These results can be further applied to facilitate the isolation and analysis of novel saccharides.

Conjugate addition of amines to chiral 3-aziridin-2-yl-acrylates

Conjugate addition of benzylamine to chiral methyl cis-3-aziridin-2-yl-acrylates was successfully proceeded to yield 3-aziridin-2-yl-3-benzylaminopropionates in high yield with high stereoselectivity. The addition products were used for the asymmetric synthesis of vicinal diamine derivatives including 4-amino-5-methylpyrrolidin-2-one, 3,4-diaminopentanoate, and 5-chloromethyl-4-alkoxycarbonylmethylimidazolidin-2-one.

Facile and practical synthesis of a cannabinoid-1 antagonist via regio- and stereoselective ring-opening of an aziridinium ion

A scalable synthetic strategy of a chiral, trisubstituted imidazolidinone ( 1), a novel cannabinoid-1 antagonist, starting from a commercially available mandelic acid ( 5) is described. The key step involves a regio- and stereoselective ring-opening of an aziridinium ion by an aniline nucleophile ( 3). A mechanistic study revealed the insight into rate amplification at a lower temperature for vicinal diamine 12 formation via a aziridinium ion 14. Although most intermediates are not isolable by crystallization due to their intrinsic physical properties (oil or foamy solid), the reported synthesis furnished pure 1 without any chromatography purification throughout the entire synthesis. Employing green chemistry principles, this novel synthesis appears to be highly efficient for the manufacturing of multi-kilogram quantities of an optically-pure active pharmaceutical ingredient.

A convenient synthesis of new diamine, amino alcohol and aminophosphines chiral auxiliaries based on limonene oxide

A strategy for the synthesis of new chiral auxiliaries based upon vicinal diamines, amino alcohols and aminophosphines, obtained from limonene oxide, has been developed. The methodology allows the preparation of (1 R,2 R,4 S)-1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diamine starting from a commercially available mixture of cis/trans (4 S)-(−)-limonene oxides, through a stereoconvergent synthetic sequence. The process starts from an inexpensive naturally occurring material, is amenable to scale-up and allows easy access to highly useful enantiopure building blocks and ligands, employed in asymmetric catalysis.

Synthesis, Electrochemistry, and Reactivity of Half-Sandwich Ruthenium Complexes Bearing Metallocene-Based Bisphosphines

The bimetallic complexes CpRu(P−P)X [Cp = η5-C5H5; X = Cl, H; P−P = dppf (1,1′-bis(diphenylphosphino)ferrocene), dppr (1,1′-bis(diphenylphosphino)ruthenocene), dppo (1,1′-bis(diphenylphosphino)-osmocene), dippf (1,1′-bis(diisopropylphosphino)ferrocene), dcpf (1,1′-bis(dicyclohexylphosphino)ferrocene)], Cp*Ru(P−P)X [Cp* = η5-C5Me5; X = Cl, H; P−P = dppf, dippf, dppomf (1,1′-bis(diphenylphosphino)octamethylferrocene), dppc (1,1′-bis(diphenylphosphino)cobaltocene)], [Cp*Ru(P−P)X]+ (X = H, CCPh; P−P = dppc+), and [Cp*Ru(P−P)L]2+ (L = CH3CN, t-BuCN; P−P = dppc+) have been synthesized. Most of the chloride and hydride complexes have been studied by cyclic voltammetry. The X-ray structures of [Cp*Ru(dppc)CH3CN][PF6]2 and [Cp*Ru(dppc)CCPh][PF6] have been determined. Protonation of [Cp*Ru(dppc)CCPh]+ gives the vinylidene complex [Cp*Ru(dppc)CCHPh]2+. The Co(III/II) potential of the dppc+ ligand undergoes a cathodic shift upon coordination in [Cp*Ru-(dppc)H]+ and an anodic shift upon coordination in [Cp*Ru(dppc)CH3CN]2+. The 1H NMR spectrum of Cp*Ru(dppc)H is consistent with its formulation as a Co(II)/Ru(II) complex. As gauged by their reactivity toward iminium cations, the hydride complexes are poor hydride donors; proton and electron transfer are dominant. CpRu(dippf)H and CpRu(dcpf)H deprotonate iminium cations with acidic α-hydrogens. Cp*Ru(dppc)H is oxidized by the N-(benzylidene)pyrrolidinium cation, giving [Cp*Ru-(dppc)H]+ and the vicinal diamine 1,2-bis(N-pyrrolidino)-1,2-diphenylethane. Most of the hydride complexes give trans-dihydride cations upon protonation; an exception is [Cp*Ru(dppc)H]+, which forms a dihydrogen complex [Cp*Ru(dppc)(H2)]2+ with surprising kinetic stability. This dihydrogen complex is more acidic and less thermodynamically stable than its dihydride isomer. The H2 ligand in [Cp*Ru(dppc)-(H2)]2+ is readily replaced by nitriles; the reaction with t-BuCN occurs by a dissociative mechanism.

ChemInform Abstract: Facile Synthesis of Vicinal Diamines via Oxidation of N‐Phenyltetrahydroisoquinolines with DDQ.

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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.

An Efficient Synthesis of 1-Acyl-3-arylimidazolidines Catalyzed by Montmorillonite K-10 Clay under Microwave Irradiation

The synthesis of 1-acyl-3-arylimidazolidines were performed by reaction of N-acyl-N -arylethylenediamines with formaldehyde and Montmorillonite clay K-10 as a catalyst under microwave irradiation. INTRODUCTION Tetrahydroimidazoles (imidazolidines) are cyclic aminals of pharmacological interest due to the bioactivity shown by some members which is closely related to the substitution type. The most studied compounds are those N,N -disubstituted ones with alkyl or aryl groups, functionalized sometimes. Accordingly, a large number of these compounds with diverse properties such as strogenic activity and mammary tumor inhibition, anti inflammatory and analgesic activity have been described in the literature. Fungicide, bactericide and antiviral activities had also been reported. On the other hand, due to the hydrophobic nature of imidazolidines they can be used to increase the bioavailability of biologically active precursors in the form of a pro-drug and they had been employed as carriers of pharmacologically active ethylenediamines or carbonyl compounds. They are also closely related to the coenzyme N,N-methylenetetrahydrofolic acid, which participate in single carbon transfer at the oxidation level of formaldehyde. Synthesis and study of this type of compounds present interest from a chemical point of view, as synthetic intermediates of cyclic and acyclic compounds with the ethylenediamine structural unit. Thus, dehydrogenation of imidazolidines leads to 4,5-dihydro-1H-imidazolium salts and their selective reduction to N,N,N -trisubstituted ethylenediamines. The imidazolidine system has been widely employed as protecting group of vicinal diamines in peptide synthesis, due to its easy cleavage in mild acid medium. Besides, imidazolidines were also employed as heterocyclic chiral auxiliaries in asymmetric synthesis. Opposite to compounds HETEROCYCLES, Vol. 78, No. 3, 2009 771

1,2-Di-tert-butylethane-1,2-diyl bis(tert-butanesulfinamide)

In the title compound, C18H40N2O2S2, a vicinal diamine derivative, the crystal structure is stabilized by two intra­molecular N—H⋯O hydrogen bonds. The distance between the two kernel chiral C atoms is 1.580 (2) Å.

The Direct Synthesis of Unsymmetrical Vicinal Diamines from Terminal Alkynes: A Tandem Sequential Approach for the Synthesis of Imidazolidinones

The combination of titanium-catalyzed anti-Markovni­kov hydroamination of terminal alkynes with the Strecker reaction is used in the synthesis of unsymmetrical vicinal diamines via the one-pot synthesis of α-cyanoamines. This methodology is further applied to the efficient synthesis of imidazolidinones. An easy-to-use bis(amidate)titanium precatalyst permits efficient approaches to heterocyclic chemistry from terminal alkynes.

Stereospecific Synthesis of Alkyl-Substituted Vicinal Diamines from the Mother Diamine: Overcoming the “Intrinsic Barrier” to the Diaza-Cope Rearrangement Reaction

Addition of isobutyraldehyde to 1,2-bis(2-hydroxyphenyl)-1,2-diaminoethane (mother diamine) cleanly gives a stable, fused imidazolidine-dihydro-1,3-oxazine ring complex. However, vigorous heating of the fused ring complex gives the diaza-Cope rearrangement product with excellent yield and stereoselectivity. A variety of alkyl aldehydes have been used to make corresponding alkyl diamines with excellent yield and stereospecificity. DFT computation shows that the intrinsic barrier for the rearrangement involving alkyl imines is about 7.9 kcal/mol greater than that involving aryl imines.

An Advance on Exploring N-tert-Butanesulfinyl Imines in Asymmetric Synthesis of Chiral Amines

Although catalytic asymmetric synthesis has undergone tremendous growth in the last 30 years, chiral auxiliary-aided asymmetric synthesis continues to attract considerable attention. Chiral N- tert-butanesulfinamide, as pioneered by Ellman and co-workers, is undoubtedly one of the most efficient auxiliaries developed to date; it allows the preparation, through simple conversion, of a diverse range of enantiopure amines, which are ubiquitous in natural products and biologically active molecules. Following on from our studies of the SmI(2)-mediated asymmetric syntheses of alpha,gamma-substituted gamma-butyrolactones, we found that simple homocoupling of chiral N- tert-butanesulfinyl imines in the presence of SmI(2) produced enantiopure vicinal C2-symmetric diamines in high yield. In addition, C2-unsymmetric chiral diamines are readily prepared through SmI(2)-mediated cross-couplings of N- tert-butanesulfinyl imines and nitrones; these transformations represented the first successful examples of asymmetric cross-coupling between two different imine species. Subsequently, we discovered another useful reaction induced by SmI(2), the efficient cross-coupling of N- tert-butanesulfinyl imines and aldehydes, which provides ready access to enantiopure anti-1,2-amino alcohols. The synthetic applicability of this reaction was demonstrated through its use in the facile total syntheses of (3R,4S)-statine, d- erythro-sphinganine, (+)-CP-99,994, and (+)-L-733,060. The Zn/In-mediated allylation of chiral N- tert-butanesulfinyl imines yields homoallylic amines. After pondering the reaction mechanism, we developed optimal reaction conditions for reversing the stereogenic outcome, thereby allowing the preparation of enantiopure homoallylic amines of either handedness from single enantiomers of the (R)- or (S)-sulfinyl imine. When a benzoyl-substituted allyl bromide is used for allylation, the reaction proceeds smoothly to give 2-vinyl-substituted anti-1,2-amino alcohols in high yields and diastereoselectivities, another simple method for preparing enantiopure amino alcohols. We employed these reactions in the syntheses of enantiopure allylglycine, 3-allyl-isoindolinones, and (-)-cytoxazone. Further studies led to the discovery that the allylations of N- tert-butanesulfinyl aldimines can be performed in water. The reactions described in this Account are among the simplest and most efficient synthetic methods available for preparing enantio-enriched diamines, amino alcohols, homoallylic amines, and other amine derivatives. These reactions are additionally attractive because of the ready availability of the starting materials, the simplicity of the reaction conditions, and the high degree of stereochemical control. Their applications in the total syntheses of several biologically interesting molecules illustrate the versatility of these transformations; we hope that they will stimulate the development of new synthetic methods.

A New Sulfa-Heterocyclic Compounds Containing Aziridine Moiety, 3-Benzyl-2-thia-1,3-diazabicyclo[3.1.0]hexane 2,2-Dioxide and Its Reaction with Nucleophiles

New sulfa-heterocyclic containing aziridine moiety derivatives such as 3-benzyl-2-thia-1,3-diazabicyclo[3.1.0]hexane 2,2-dioxide has been obtained starting from 2-benzyl-4-chloromethyl-1,2,5-thiadiazolidine 1,1-dioxide in alkaline conditions. The aziridine moiety was opened by various nucleophiles to give vicinal diamines which used as an intermediate in the preparation of other bicyclic compounds with orthogonal protections such as 2,5-dibenzyl-l,2,5-thiadiazolo[2,3-a]pyrazine 1,1-dioxide in good yield.

Self-Assembly of Noncyclic Bis-d- and l-tripeptides into Higher Order Tubular Constructs: Design, Synthesis, and X-ray Crystal Superstructure

Trans (1R,2R)-diaminocyclohexane was used as a semirigid vicinal diamine to anchor two N-protected tripeptides consisting of L-D-L amino acids as carboxy terminal amides. The bis-tripeptide consisting of L-Ser (OBn)-D-Ser (OBn)-L-Ser (O-p-bromobenzyl) Boc afforded X-ray quality crystals containing benzene and chloroform solvent molecules. Analysis of the solid-state structure revealed a highly H-bonded helical open-ended tubular superstructure. The tripeptide strands intertwine like a pair of self-embracing arms, held together by a gamma-turn and a 14-membered antiparallel H-bonded macroring spanning the first and third amino acid residues within each strand. Whereas the tripeptide from the R,R anchor gave beautiful crystals from benzene and chloroform, the analogous construct from the S,S-anchored diamine gave a gel. Related bis-tripeptides with different amino acids showed extensive intramolecular H-bonding based on NMR titration and dilution experiments.