An experimental and computational study of the enantioselective lithiation of N-Boc-pyrrolidine using sparteine-like chiral diamines

The enantioselective lithiation of N-Boc-pyrrolidine using sec-butyllithium and isopropyllithium in the presence of sparteine-like diamines has been studied experimentally and computationally at various theoretical levels through to B3P86/6-31G*. Of the (-)-cytisine-derived diamines (N-Me, N-Et, N-(n)Bu, N-CH(2)(t)Bu, N-(i)Pr) studied experimentally, the highest enantioselectivity (er 95:5) was observed with the least sterically hindered N-Me-substituted diamine, leading to preferential removal of the pro-R proton i.e., opposite enantioselectivity to (-)-sparteine. The experimental result with the N-Me-substituted diamine correlated well with the computational results: at the B3P86/6-31G* level, the sense of induction was correctly predicted; the lowest energy complex of isopropyllithium/diamine/N-Boc-pyrrolidine also had the lowest activation energy (DeltaH++ = 11.1 kcal/mol, DeltaG++= 11.5 kcal/mol) for proton transfer. The computational results with the N-(i)Pr-substituted diamine identified a transition state for proton transfer with activation energies of DeltaH++= 11.7 kcal/mol and DeltaG++= 11.8 kcal/mol (at the B3P86/6-31G* level). Although comparable to (-)-sparteine and the N-Me-substituted diamine, these DeltaH++ and DeltaG++ values are at odds with the experimental observation that use of the N-(i)Pr-substituted diamine gave no product. It is suggested that steric crowding inhibits formation of the prelithiation complex rather than increasing the activation enthalpy for proton transfer in the transition state. Three other ligands (N-H and O-substituted as well as a five-membered ring analogue) were studied solely using computational methods, and the results predict that the observed enantioselectivity would be modest at best.     

Synthesis of sparteine-like chiral diamines and evaluation in the enantioselective lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine

Three chiral diamines were synthesised and evaluated as sparteine surrogates in the lithiation-substitution of N-(tert-butoxycarbonyl)pyrrolidine. The synthesis and attempted resolution of sparteine-like diamines [(1S*,2R*,8R*)-10-methyl-6,10-diazatricyclo[6.3.1.0(2,6)]dodecane and (1S*,2R*,9R*)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane] (via inclusion complex formation) are reported. Unfortunately, it was only possible to resolve the diazatricyclo[7.3.1.0(2,7)]tridecane compound. An alternative route to (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane starting from the natural product, (-)-cytisine, is described. This simple three-step route furnished gram-quantities of a (+)-sparteine surrogate. X-Ray crystallography of an intermediate in the route, (1R,5S,12S)-3-methoxycarbonyldecahydro-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one, enabled the stereochemistry of all of the tricyclic diamines described in this paper to be unequivocally established. Two other diamines, starting from (S)-proline and resolved 2-piperidine ethanol, were prepared using standard methods. These diamines lacked the bispidine framework of (-)-sparteine and were found to impart vastly inferior enantioselectivity. It was concluded that, for the asymmetric lithiation substitution of N-Boc pyrrolidine, a rigid bispidine framework and only three of the four rings of (-)-sparteine are needed for high enantioselectivity. Furthermore, it is shown that diamine (1R,2S,9S)-11-methyl-7,11-diazatricyclo[7.3.1.0(2,7)]tridecane is the first successful (+)-sparteine surrogate.     

Highly Enantioselective Direct Synthesis of Endocyclic Vicinal Diamines through Chiral Ru(diamine)‐Catalyzed Hydrogenation of 2,2′‐Bisquinoline Derivatives

An asymmetric hydrogenation of 2,2′‐bisquinoline and bisquinoxaline derivatives, catalyzed by chiral cationic ruthenium diamine complexes, was developed. A broad range of chiral endocyclic vicinal diamines were obtained in high yields with excellent diastereo‐ and enantioselectivity (up to 93:7 dl/meso and >99 % ee). These chiral diamines could be easily transformed into a new class of chiral N‐heterocyclic carbenes (NHCs), which are important but difficult to access.     

Synthesis of organo soluble aromatic poly(amide-imide)s based on 2-(5-(3,5-dinitrophenyl)-1,3,4-oxadiazole-2-yl)pyridine in an ionic liquid

In this work,the syntheses of new thermally stable poly(amide-imide)s with pendant 2-pyridyl-1,3,4-oxadiazole units in n-butyl methyl imidazolium bromide as reaction media have been reported.A new dicarboxylic acid has been derived from the reaction of diamine,2-(5-(3,5-diaminophenyl)-1,3,4-oxadiazole-2-yl)pyridine(POBD),and trimellitic acid anhydride.Polymers were prepared from the reaction of the diimide-diacid(DIDA) and different aromatic diamines in butyl methyl imidazolium bromide,[bmim][Br],in the ...     

Synthesis and characterization of novel heat resistant poly(amide imide)s

A series of new poly(amide imide)s was prepared from new diacid containing sulfone, ether, amide and imide groups with various aromatic diamines. The diacid was synthesized via four steps, starting from reaction of 4-aminophenol with 4-nitrobenzoyl chloride in the presence of propylene oxide afforded N-(4-hydroxy phenyl)-4-nitrobenzamide. In the second step, reduction of nitro group resulted in preparation of 4-amino-N-(4-hydroxy phenyl) benzamide. In the next step for the preparation of diamine, the reaction of 4-amino-N-(4-hydroxy phenyl) benzamide with bis-(4-chlorophenyl) sulfone in the presence of K₂CO₃ was achieved. The prepared sulfone ether amide diamine was reacted with two moles of trimellitic anhydride to synthesize related sulfone ether amide imide diacid. The precursors and final monomer were characterized by FT-IR, H-NMR and elemental analysis. Direct polycondensation reaction of the sulfone ether amide imide diacid with different diamines in the presence of triphenyl phosphite afforded five different poly (sulfone ether amide imide amide)s. The obtained polymers were fully characterized and their physical properties including thermal behavior, thermal stability, solubility, and inherent viscosity were studied.     

13C-NMR Sequence Analysis. 23. Synthesis and NMR Spectroscopic Characterization of Polyoxamides with Alternating and Random Sequences of Aliphatic Diamines

Three classes of polyoxamides were prepared: homopolymers derived from α-, ω-diaminoalkanes, and 4,4′-diaminodiphenyl-methane, copolymers with an alternating sequence of two different aliphatic diamines and copolymers with a random sequence of two different diamines. For their syntheses a new class of monomers, the diamine bisoxamide diethyl esters, were prepared from α,ω-diamines and oxalic acid chloride ethyl ester. The 22.63 MHz ¹³C-NMR spectra of the polyoxamide solution in fluorosulfonic acid permitted sequence analysis because the carbonyl signals are sensitive to the nature of the neighboring diamine units. In contrast, 9.12 MHz ¹⁵N-NMR spectra did not give any sequence information. The thermal stability of the polyoxamides was investigated, but differential scanning calorimetry did not give useful information on the crystallinity of the polyoxamides because of their thermal degradation.     

Melt amination of polypropylenes

Amine (primary and secondary) functional polypropylenes were prepared by the melt blending of maleated polypropylenes with small diamines, including hexamethylenediamine (primary–primary diamine), p‐xylylenediamine (primary–primary diamine), and N‐hexylethylenediamine (primary–secondary diamine), at various diamine/anhydride molar ratios in a batch mixer and a twin‐screw extruder. The experimental conversion data by Fourier transform infrared nearly agreed with the assumption of a complete reaction between the primary amine and anhydride. Chain extensions of the maleated polypropylenes by the diamines were monitored by the torques during mixing and further evaluated by rheological (dynamic shear rheometry) and mechanical measurements. We show that these amino polypropylenes are very effective adhesion promoters and compatibilizers of thermoplastic polyurethanes with polypropylene. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4217–4232, 2005     

Diglycidylphenylphosphate based fire retardant liquid crystalline thermosets

Organophosphorus liquid crystalline thermosets (LCTs) were developed using diglycidylphenylphosphate (DGPP) and various aromatic diamines. DGPP was prepared by the esterification of phenylphosphorodichloridate with glycidol. 2,5-Bis(p-aminophenyl)-1,3,4-oxadiazole (BPOD) was synthesized and three different commercial diamines, 4,4′-diaminodiphenyl sulphone (DDS), 4,4′-diaminodiphenyl methane (DDM) and biphenyl diamine (BPD) were used as curing agents. The mesomorphic behaviour of DGPP/diamine mixtures and their curing kinetics were monitored by differential scanning calorimetry and hot stage optical polarized microscopy. The thermogravimetric analysis data showed that the LCTs are stable in the range 261-292 °C and afford 36-48% char yield. The limiting oxygen index values are between 35 and 47 proving fire retardance. The mechanical properties of the cured LCTs were characterized by dynamic mechanical analysis.     

Synthesis and antiviral activities of N-mono- and/or N,N'-di-carbamoyl and acyl derivatives of symmetrical diamines

N-carbamoyl and N-acyl diamine derivatives were synthesized from symmetrical diamines by their addition to iso(thio)cyanates, cleavage reaction of acid anhydride, or N-acylation by acyl chloride. (1R,2R)-1,2-Diaminocyclohexane [(1R,2R)-1], meso-1,2-diaminocyclohexane (meso-1), (1R,2R)-1,2-diphenylethylenediamine [(1R,2R)-3], or meso-1,2-diphenylethylenediamine (meso-3) were used as the starting symmetrical diamines. The target compounds synthesized herein were evaluated for antiviral activity with herpes simplex virus type 1 (HSV-1). A few derivatives of 1,2-diaminocyclohexane [(1R,2R)-7aa and cis-7b] with adamantyl group(s) showed significant antiviral activity (EC(50)=16.0, 27.0 microg/ml).     

The effects of ligand variation on enantioselective hydrogenation catalysed by RuH2(diphosphine)(diamine) complexes

Density functional theory calculations have been used to investigate the hydrogenation of acetophenone (ACP) catalysed by the RuH(2)(diphosphine)(diamine) complexes with emphasis on the effect of the structure of the diphosphine and diamine ligands on the enantioselectivity. The computed reaction coordinate diagrams of RuH(2)(diphosphine)[(S,S)-DPEN] catalysed reactions with different (S)-diphosphine ligands (XylBINAP, TolBINAP, and BINAP) show that the presence of two methyl groups in the meta position is critical to obtaining a high difference in activation energy for the reaction pathways associated with the (R)- and (S)-alcohols, and consequently high enantioselectivity. The effect of the diamine structure while keeping the TolBINAP and XylBINAP fixed has also been analysed. To enhance the enantioselectivity of the TolBINAP system, the addition of two methyl groups and the removal of a phenyl group of the diamine (DMAPEN) offer the necessary steric interactions. We conclude by reporting a correlation between the enantiomeric excess and the difference in the computed activation energies of the two most favourable (S) and (R) reaction pathways, which shows that the computational procedure adopted could be used to predict the enantiomeric excess of ketone hydrogenation reactions catalysed by the Noyori-type catalysts, and assist in the choice of ligand when optimising the enantiomeric excess.     

Synthesis and application of a new pseudo C2-symmetric tertiary diamine for the enantioselective addition of MeLi to aromatic imines

A new tertiary pseudo C₂-symmetric diamine derived from (1S,2S)-(+)-pseudoephedrine was synthesized and tested in the enantioselective addition of methyllithium on different aromatic imines. A comparative study with a similar C₂-symmetric ligand derived from the cyclohexane diamine showed better reactivity and enantioselectivity up to 91%.     

Stereocontrolled synthesis of vicinal diamines by organocatalytic asymmetric Mannich reaction of N-protected aminoacetaldehydes: formal synthesis of (-)-agelastatin A

The 1,2-diamine (vicinal diamine) motif is present in a number of natural products with interesting biological activity and in many chiral molecular catalysts. The efficient and stereocontrolled synthesis of enantioenriched vicinal diamines is still a challenge to modern chemical methodology. We report here both syn- and anti-selective asymmetric direct Mannich reactions of N-protected aminoacetaldehydes with N-Boc-protected imines catalyzed by proline and the axially chiral amino sulfonamide (S)-3. This organocatalytic process represents the first example of a Mannich reaction using Z- or Boc-protected aminoacetaldehyde as a new entry of α-nitrogen functionalized aldehyde nucleophile in enamine catalysis. The obtained optically active vicinal diamines are useful chiral synthons as exemplified by the formal synthesis of (-)-agelastatin A.     

Crosslinking in Acetoacetoxy Functional Waterborne Crosslinkable Latexes

Chain crosslinking through the different stages of the production of acetoacetoxy ethyl methacrylate (AAEMA) containing acrylic latexes was studied; namely, during the synthesis step, after latex neutralization and after crosslinking with diamines. The gel content of the latex increased with increasing amounts of the functional AAEMA monomer likely due to dimethacrylate impurities contained in the monomer. Moreover, the neutralization of the latex with ammonia had important implications in the microstructure of the polymer. A base catalyzed Michael addition reaction between acetaocetoxy groups and terminal double bonds present in the polymer particles produced chain pre-crosslinking that affected the further crosslinking reaction with diamines. The compatibility of the diamines with the polymer matrix and the ratio diamine/acetoacetoxy used to crosslink the latex during film formation also played an important role in the crosslinking efficiency as evaluated by solvent resistance of crosslinked films.     

Highly regioselective synthesis of chiral diamines via a Buchwald–Hartwig amination from camphoric acid and their application in the Henry reaction

In this work the synthesis of new asymmetric diamine ligands from camphoric acid is described. The new diamines can be directly prepared in a regioselective arylation of the less hindered primary amine group of (+)‐cis‐1,2,2‐trimethylcyclopentane‐1,3‐diamine via a Buchwald–Hartwig amination in high yields. The resulting diamines incorporate a secondary and primary amine group and were successfully applied as ligands in a copper‐catalyzed Henry reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

Complexation of rhodium(II) tetracarboxylates with aliphatic diamines in solution: 1H and 13C NMR and DFT investigations

The complexation of rhodium(II) tetraacetate, tetrakistrifluoroaceate and tetrakisoctanoate with a set of diamines (ethane‐1,diamine, propane‐1,3‐diamine and nonane‐1,9‐diamine) and their N,N′‐dimethyl and N,N,N′,N′‐tetramethyl derivatives in chloroform solution has been investigated by ¹H and ¹³C NMR spectroscopy and density functional theory (DFT) modelling. A combination of two bifunctional reagents, diamines and rhodium(II) tetracarboxylates, yielded insoluble coordination polymers as main products of complexation and various adducts in the solution, being in equilibrium with insoluble material. All diamines initially formed the 2 : 1 (blue), (1 : 1)_n oligomeric (red) and 1 : 2 (red) axial adducts in solution, depending on the reagents' molar ratio. Adducts of primary and secondary diamines decomposed in the presence of ligand excess, the former via unstable equatorial complexes. The complexation of secondary diamines slowed down the inversion at nitrogen atoms in NH(CH₃) functional groups and resulted in the formation of nitrogenous stereogenic centres, detectable by NMR. Axial adducts of tertiary diamines appeared to be relatively stable. The presence of long aliphatic chains in molecules (adducts of nonane‐1,9‐diamines or rhodium(II) tetrakisoctanoate) increased adduct solubility. Hypothetical structures of the equatorial adduct of rhodium(II) tetraacetate with ethane‐1,2‐diamine and their NMR parameters were explored by means of DFT calculations. Copyright © 2013 John Wiley & Sons, Ltd.     

A Rapid HPLC Determination of C2–C7 Aliphatic Diamines by Precolumn Derivatization with Acetylacetone in Methanol-Water

A rapid reversed-phase high performance liquid chromatographic analysis for the determination of seven aliphatic diamines in water is described. Precolumn derivatization with acetylacetone is used for traces of aliphatic diamines in water-methanol (10:1 v/v) medium. The acetylacetone derivatives obtained after 15 min were extracted with an octadecylsilane functionalized silica cartridge, and then injected into the HPLC system. The HPLC system consisted of a reversed-phase column, and a spectrophotometric detector adjusted to 310 nm as elution solvent a methanol-tetrahydrofuran-water (55:3:42 v/v) mixture was used. The acetylacetone derivatives of the C2-C7 diamines were separated with a good resolution in 23 min. The detection limits achieved for each diamine were between 0.18-0.72 ng/ml for a 100 ml water sample. The recovery of diamine derivatives from river and seawater was 88-101%, with relative standard deviations of 2.2-4.0%, and 82-93%, with relative standard deviations of 2.8-4.6%, respectively. Aliphatic diamines are widely used as chemical reagents, occur as metabolic in biomedical studies and are used as chelating agents in analytical chemistry. As they are soluble in water, their use results in their ultimate release to the environment. The need for a sensitive, selective and rapid determination of aliphatic diamines in environmental samples thus has become important. Dobberpuhl et al. [1] have described a highly sensitive pulsed electrochemical detection for aliphatic monoamines and diamines following their chromatographic separation. Although, it is a sensitive method the determination has to be carried out in alkaline conditions. The most common method for the determination of aliphatic amines is high performance liquid chromatography (HPLC), using different derivatives with either fluorescence [2-5] or UV-visible detection [6-11]. The fluorescence detection method most often relies on post-column derivatization, which requires a second pump to deliver the reagent. Acetylacetone is soluble to some degree in water, and has been used as a pre-column derivatization reagent [12]. The reaction only is effective with diamines, and results in UV-active acetylacetone derivatives known as Schiff bases. But acetylacetone requires a long reaction time in water, which makes it rather unsuitable for routine analysis. In this paper an optimized reversed-phase HPLC determination procedure for C2-C7 aliphatic diamines at low ng/ml levels in water is described.     

水相不对称转移氢化*

手性醇和胺是重要的精细化学品,不对称转移氢化是获得这类手性化合物有效、实用的途径之一。在众多的催化剂中,Noyori等发展的手性二胺与过渡金属钌TsDPEN-Ru（TsDPEN = 1,2-二苯基乙二胺）络合物是最有效的催化剂。近年来,随着化学家对绿色化学的日益重视,水作为绿色溶剂被广泛地用作为不对称催化转移氢化的反应介质,具有很高的反应活性、对映选择性和化学选择性。本文综述近年来应用未经修饰和修饰的手性二胺配体与过渡金属钌[(cymene)RuCl₂]₂、铑[(Cp*)RhCl₂]₂和铱[(Cp*)IrCl_2]2的络合物催化的水相中酮、亚胺和活化烯烃的不对称转移氢化的研究进展。     

A practical and efficient synthesis of chiral N,N-disubstituted C2 symmetric diamines derived from (R,R)-1,2-diaminocyclohexane

An improved synthesis of chiral diamine ligands derived from (R,R)-1,2-diaminocyclohexane is described, providing N-substituted diamines. The synthesis of other new ligands based on this methodology is also reported.     

Use of copper(II)/diamine catalysts in the desymmetrisation of meso-diols and asymmetric Henry reactions: comparison of (−)-sparteine and (+)-sparteine surrogates

Four new copper(II)/diamine complexes comprising some (+)-sparteine surrogates and a cyclohexane-derived diamine were prepared and evaluated as chiral catalysts in desymmetrisation of meso-diols and asymmetric Henry reactions. Mono-benzoylation reactions generated two products with high enantioselectivity (90:10 to 97:3 er). Asymmetric Henry reactions gave nitro alcohols in 90:10 to 98:2 er. Notably, the sense of induction with the (+)-sparteine surrogates was opposite to that obtained using the copper(II)/(−)-sparteine complex. One of the nitro alcohol products was utilised in a concise synthesis of a chiral morpholine.     

Synthesis and structural chemistry of alkali metal tris(HMDS) magnesiates containing chiral diamine donor ligands

Six alkali metal tris(HMDS) magnesiate complexes (HMDS, 1,1,1,3,3,3,-hexamethyldisilazide) containing chiral diamine ligands have been prepared and characterised in both the solid- and solution-state. Four of the complexes have a solvent-separated ion pair composition of the form [{M·(chiral diamine)(2)}(+){Mg(HMDS)(3)}(-)] [M = Li for 1 and 3, Na for 2 and 4; chiral diamine = (-)-sparteine for 1 and 2, (R,R)-TMCDA for 3 and 4, (where (R,R)-TMCDA is N,N,N',N'-(1R,2R)-tetramethylcyclohexane-1,2-diamine)] and two have a contacted ion pair composition of the form [{K·chiral diamine}(+){Mg(HMDS)(3)}(-)](n) [chiral diamine = (-)-sparteine for 5 and (R,R)-TMCDA for 6]. In the solid-state, complexes 1-4 are essentially isostructural, with the lithium or sodium cation sequestered by the respective chiral diamine and the previously reported anion consisting of three HMDS ligands coordinated to a magnesium centre. As such, complexes 1-4 are the first structurally characterised complexes in which the alkali metal is sequestered by two molecules of either of the chiral diamines (-)-sparteine (1 and 2) or (R,R)-TMCDA (3 and 4). In addition, complex 4 is a rare (R,R)-TMCDA adduct of sodium. In the solid state, complexes 5 and 6 exist as polymeric arrays of dimeric [{K·chiral diamine}(+){Mg(HMDS)(3)}(-)](2) subunits, with 5 adopting a two-dimensional net arrangement and 6 a linear arrangement. As such, complexes 5 and 6 appear to be the only structurally characterised complexes in which the chiral diamines (-)-sparteine (5) or (R,R)-TMCDA (6) have been incorporated within a polymeric framework. In addition, prior to this work, no (-)-sparteine or (R,R)-TMCDA adducts of potassium had been reported.