Synthesis of enantiomerically pure 2-(N-aryl,N-alkyl-aminomethyl)aziridines: a new class of ligands for highly enantioselective asymmetric synthesis

A simple and effective synthesis of enantiomerically pure 2-(N-aryl-, N-alkyl-aminomethyl)aziridines from (2S)-N-tritylaziridine-2-carboxylic acid methyl ester has been developed. Treating of this key ester with several primary and secondary amines in the presence of AlMe₃ provided the corresponding chiral N-trityl-2-carboxamides, and their reduction performed with different reagents resulted in the formation of the expected 2-(aminomethyl)aziridines. The choice of reaction conditions allows to either keep or leave the trityl substituent in the product. Such 2-(aminoalkyl)aziridines have shown very high catalytic efficiency in the asymmetric arylation of aldehydes and in other testing asymmetric reactions. On the other hand, homochiral N-trityl-2-carboxamides are interesting building blocks for the synthesis of various biologically active compounds.     

Ultrafast organocatalytic ring-opening polymerization of N-sulfonyl aziridine in the melt

An ultrafast approach for controlled synthesis of well-defined polysulfonamides is established through organocatalytic anionic ring-opening polymerization (ROP) of N-sulfonyl aziridine in the melt. Several different organobases are investigated, and it is found that N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA) catalyzed ROP of 2-methyl-N-tosylaziridine (TsMAz) gives the desired polymer, while 1,4-diazabicyclo[2.2.2]octane (DABCO) and 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) initiate the polymerization along with initiator to produce uncontrolled polymers. Using PMDETA as the catalyst, poly(2-methyl-N-tosylaziridine) with molecular weight over 100 kg/mol can be synthesized in less than 90 s. Various initiators, including carboxylic acid, N-sulfonyl amide, unactivated amine, phenol, and thiol, are applicable for this protocol to give the molecular weight and end-group controlled polymers under the open-flask condition. Combining this ultrafast ROP with ring-opening metathesis polymerization (ROMP), a brush copolymer is facile synthesized. This approach allows the ultrafast metal-free synthesis of polysulfonamide and expands the scope of initiators for the ROP of N-sulfonyl aziridines.     

One-pot tandem ring-opening polymerization of N-sulfonyl aziridines and “click” chemistry to produce well-defined star-shaped polyaziridines

An effective approach for fast synthesis of well-defined star-shaped poly(2-methyl-N-tosylaziridine)s was developed by one-pot tandem ring-opening polymerization (ROP) of N-sulfonyl aziridines with trimethylsilyl azide (TMSN₃) and “click” reaction with alkynes. Azido terminated polyaziridines (α-N₃-PAzs) could be achieved via ROP of N-sulfonyl aziridines with TMSN₃ in the presence of organic superbases. The catalytic efficiency of organobases, including 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-diazabicyclo[5.4.0]-7-undecene (DBU), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), and N,N,N′,N″,N″-pentamethyldiethylenetriamine (PMDETA), was evaluated, and all of them except TBD afforded “living”/controlled ROP of 2-methyl-N-tosylaziridines (TsMAz). Star-shaped polyaziridines were then fastly synthesized by the one-pot tandem strategy. During the reaction process, PMDETA catalyzed ROP first, then was triggered to be a ligand by adding CuBr for “click” reaction. Well-defined 3- and 4-arm star P(TsMAz)s were successfully prepared, and subsequently desulfonylated to give star-shaped polypropylenimines (PPIs). PPI stars exhibited intrinsic photoluminescence properties from the polyamine arms.     

Ring Opening of N‐Sulfonyl Aziridines by Amines in Silica‐Water

Ring opening reactions of N‐sulfonyl aziridines by primary and secondary amines in silica gel (SG)‐water system were achieved, which provided a mild, practical and environmentally benign method to synthesize mono‐ and bis‐sulfonyl substituted amines. When primary and secondary amines were used in excess, they reacted with N‐sulfonyl aziridines smoothly at room temperature, mainly affording 1:1 ring opening products. Reactions of primary amines with 2 equiv. of aziridines produced 2:1 ring opening products. Some 1:1 products can be cyclized with CS₂ to synthesize N‐sulfonyl cyclothioureas also in water.     

Synthése,stéréochimie,et réactivité thermique de (N-méthylidenealkylamino)-2 aziridines

1-Alkyl-2-(N-methylidenealkylamino)aziridines are obtained by the reaction of primary amines with either α-chloroacraldehyde or α-chlorocrotonaldehyde. Structural assignments are made by nmr spectroscopy. The thermal rearrangement of 1-alkyl-2-(N-methylidenealkylamino)-3-methylaziridines to pyrroles is described.     

1,5-Polymerization of 1-thioacylaziridines

Four thioacylaziridines, 1-thioaroyl-, 1-(N-phenylthiocarbamyl)-, 1-(aryloxythiocarbonyl)-, and 1-(aryldithiooxycarbonyl)aziridines, were found to undergo 1,5-polymerization to giving polymers of polyiminothioether, polyisothiourea, polyiminothiocarbonate, and polyiminodithiocarbonate structure, respectively. The 1,5 polymerization may be explained by the kinetic factors rather than the thermodynamic ones.     

Comparing Cyclophellitol N‐Alkyl and N‐Acyl Cyclophellitol Aziridines as Activity‐Based Glycosidase Probes

The synthesis and evaluation as activity‐based probes (ABPs) of three configurationally distinct, fluorescent N‐alkyl cyclophellitol aziridine isosteres for profiling GH1 β‐glucosidase (GBA), GH27 α‐galactosidase (GLA) and GH29 α‐fucosidase (FUCA) is described. In comparison with the corresponding acyl aziridine ABPs reported previously, the alkyl aziridine ABPs are synthesized easily and are more stable in mild acidic and basic media, and are thus easier to handle. The β‐glucose‐configured alkyl aziridine ABP proves equally effective in labeling GBA as its N‐acyl counterpart, whereas the N‐acyl aziridines targeting GLA and FUCA outperform their N‐alkyl counterparts. Alkyl aziridines can therefore be an attractive alternative in retaining glycosidase ABP design, but in targeting a new retaining glycosidase both N‐alkyl and N‐acyl aziridines are best considered at the onset of a new study.     

Anionic polymerization of N-ethyl-2-vinylcarbazole and N-ethyl-3-vinylcarbazole

The polymerization of N-ethyl-2-vinylcarbazole and N-ethyl-3-vinylcarbazole by an anionic mechanism has been demonstrated. Polymerization reactions were monitored by ultraviolet/visible spectroscopy and λ_max and ε values for the propagating carbanions determined. The 2-vinyl monomer exhibits all the features of a standard “living” polymer; the carbanion is stable at ambient temperatures and high molecular weight, M?_n ? 10⁶, narrow distribution polymers and block copolymers with styrene have been prepared. The carbanion from the 3-vinyl monomer is much less stable and a clean polymerization can only be conducted at temperatures below -60°C. A comparison of the anionic polymerization characteristics of the N-, 2-, and 3-vinyl carbazole monomer series is presented.     

Hydrophilic magnetic polymer latexes. 2. Encapsulation of adsorbed iron oxide nanoparticles

The encapsulation of seed polymer particles coated by anionic iron oxide nanoparticles has been investigated using N-isopropylacrylamide as a main monomer, N,N-methylene bisacrylamide as a crosslinking agent, itaconic acid as a functional monomer and potassium persulfate as an anionic initiator. The magnetic latexes obtained have been characterized with regard to particle size, iron oxide content and electrophoretic mobility. All these properties have been examined by varying several polymerization parameters: reaction medium, monomer(s) and crosslinking agent concentrations, nature of seed latexes and type of polymerization (batch versus shot process). The magnetic content in the polymer microspheres strongly depends on the polymerization procedure (i.e., encapsulation process) and varies between 6 and 23 wt%, and monodisperse magnetic polymer particles were obtained. Received: 28 December 1999 Accepted in revised form: 15 June 1999     

Stereoselective Lewis Acid Mediated (3+2) Cycloadditions of N‐H‐ and N‐Sulfonylaziridines with Heterocumulenes

Alkyl and aryl isothiocyanates and carbodiimides are effective substrates in (3+2) cycloadditions with N‐sulfonyl‐2‐substituted aziridines and 2‐phenylaziridine for the synthesis of iminothiazolidines and iminoimidazolidines. Additionally, the stereoselective (3+2) cycloaddition of N‐H‐ and N‐sulfonylaziridines with isothiocyanates can be accomplished, allowing for the synthesis of highly enantioenriched iminothiazolidines. Evidence for an intimate ion‐pair mechanism is presented herein in the context of these chemo‐, regio‐, and diastereoselective transformations. The demonstrated ability to remove the sulfonyl group from the heterocyclic products displays the utility of these compounds for further derivatization and application.     

Thermal and radiation-induced polymerizations of N-tert-butylacrylamide and (N-tert-butylacrylamide)2–ZnCl2 complex

The thermal and radiation-induced in-source and postirradiation polymerizations of N-tert-butylacrylamide and (N-tert-butylacrylamide)₂–ZnCl₂ complex of this monomer were studied at various temperatures. In in-source, solid-state polymerizations of monomer and complex the conversion was about 95% at 21°C in about eight days. Their postirradiation polymerizations were also studied in solid state. The conversion-time curves of these two systems show an autoacceleration as in-source polymerization. In both types of polymerization the overall rate of polymerization of complex was higher than that of pure monomer at the same polymerization temperature. In investigations of the thermal polymerization of N-tert-butylacrylamide and ZnCl₂-complex it was observed that the ZnCl₂-complex system can be polymerized in air in the molten and solid state. The conversion of monomer to polymer reaches limiting values in solid state in about 1 hr. The thermal polymerization of ZnCl₂-complex in the molten state was also studied and 100% conversion was obtained in 30 min. The thermal polymerization of pure monomer was studied in vacuum and an appreciable amount of polymer was obtained in the molten state; however, the thermal polymerization of this monomer is negligible in solid state. In this work rates of polymerization for N-tert-butylacrylamide and (N-tert-butylacrylamide)₂–ZnCl₂ are compared under various experimental conditions and overall activation energies are calculated.     

Novel synthesis of 2-aminopentanedinitriles from 2-(bromomethyl)aziridines and their transformation into 2-imino-5-methoxypyrrolidines and 5-methoxypyrrolidin-2-ones

1-Arylmethyl-2-(bromomethyl)aziridines were transformed into 2-[N-(arylmethyl)amino]pentanedinitriles upon treatment with an excess of potassium cyanide in DMSO through an unprecedented and peculiar reaction mechanism, involving base-induced ring opening of intermediate 2-(cyanomethyl)aziridines into allylamines, followed by migration of the double bond out of the conjugation towards aldimines via enamine intermediates. The resulting aminopentanedinitriles served as substrates for the synthesis of novel 2-imino-5-methoxypyrrolidines upon treatment with sodium methoxide in methanol, which were either acetylated at the free imino group to afford the more stable N-acetylimino derivatives or hydrolyzed towards the corresponding synthetically relevant 5-methoxypyrrolidin-2-ones.     

Regioselective Ring‐Opening of Amino Acid‐Derived Chiral Aziridines: an Easy Access to cis‐2,5‐Disubstituted Chiral Piperazines

An efficient four‐step synthetic strategy for cis‐2,5‐disubstituted chiral piperazines derived from amino‐acid‐based aziridines is described. The key steps in this strategy are the highly regioselective boron trifluoride diethyl etherate (BF₃ ⋅ OEt₂)‐mediated ring‐opening of less‐reactive N‐Ts chiral aziridines by α‐amino acid methyl ester hydrochloride followed by Mitsunobu cyclization. This protocol has been used in an attempt to construct the piperazine core framework of natural product (+)‐piperazinomycin.     

Oligomers Derived from 2-Oxazolines

This paper describes the synthesis and properties of oligomer chains derived from 2-oxazolines. First, poly(styrene-g-N-acetyl-ethylenimine) was prepared, and its hydrolysis gave poly(styrene-g-ethylenimine) which showed good chelating properties. Secondly, ABA type triblock copolymers were prepared in which an N-acylethylenimine chain is used as A block and ethylene oxide chain is employed as B block. These triblock copolymers showed good compatibility with Nylon 6, which were shown to posecess effective anti-electrostatic properties for Nylon 6. Thirdly, AB type block copolymers from 2-oxazolines have been prepared by using living polymerization technique. These block copolymers are soluble in water and showed good surfactant nature as reflected by surface tension (γ), when A block is consisted from N-acetyl- or N-propionylethylenimine chain (hydro-philic) and B block is made of N-tridecanoyl or N-aroylethylenimine chain (lipophilic). Finally, graft copolymers of cellulose diacetate having N-acetylethylenimine chain were prepared. It has been found by using a rheovibron that these graft copolymers are compatible with poly(vinyl chloride).     

Polymerization of N-(fluoro phenyl) maleimides

Poly(N-aryl maleimide)s of characteristic structures have been synthesized and some of their physical properties studied. These include N-(2-fluoro phenyl), N-(3-fluoro phenyl), N-(4-fluoro phenyl), N-(2,4-difluoro phenyl), N-(2,5-difluoro phenyl), N-(2,3,5,6-tetrafluoro phenyl), and N-(pentafluoro phenyl). The polymerization of N-(fluoro phenyl) maleimides by free-radical initiation in bulk or in solution and by anionic catalyst have been studied to compare the characteristics of polymerization by γ-ray irradiation with that by free-radical initiation. The polymers were characterized by elemental analysis, intrinsic viscosity, spectroscopy (IR and NMR), programmed thermogravimetric analysis, and x-ray diffraction. Spectra of polymers prepared by radiation and anionic polymerization were nearly identical with those of polymers prepared by free-radical polymerization initiated by AIBN in bulk or in solution and by the self-initiated thermal polymerization. A variety of reaction conditions were tried, but all attempts to change the molecular structure of the polymers were unsuccessful. Rates of thermal degradation for poly[N-(fluoro phenyl) maleimide]s have been analyzed by using a multiple-heating-rate procedure. Overall activation energy, order of reaction, and frequency factor have been evaluated. On the basis of the comparison between the overall activation energy of the thermal degradation of poly[N-(fluoro phenyl) maleimide]s and NMR spectra of their corresponding monomers, it can be concluded that the ¹H shifts due to ethylenic protons are so characteristic in sign and magnitude as to be useful in thermal stability elucidation. Some qualitative explanations were given on the stability of these polymers as affected by the type and size of the substituent. The x-ray diffractograms of all samples show two rather broad peaks indicative of noncrystalline structures. The location of the peaks does not depend upon preparation conditions and temperature. Poly(N-maleimide)s of fluoroanilines have not been hitherto described.     

Propene polymerization with rac-Me2Si(2-Me-Benz[e]Ind)2ZrX2 [X = Cl,Me] using different cation-generating reagents

Propene was polymerized with methylaluminoxane (MAO) and cationic activated rac-dimethylsilylene-2-methylbenz[e]indenylzirconocene [ MBI-Cl ₂] and [ MBI-Me ₂]. For cationic activation of the MBI-Me ₂ system tris(pentafluorophenyl)borane [I], N,N-dimethylanilinium tetra(pentafluorophenyl)borate [III] were used. The MAO-activated dimethyl complex showed higher activity with respect to the dichloride system using high catalyst concentrations and [Al]/[Zr] ratios. Most effective cationic activator for MBI-Me ₂ was N,N-dimethylanilinium tetra(pentafluorophenyl)borate [II] in combination with Al(i-Bu₃). Using tris(pentafluorophenyl)borane [I] at different polymerization conditions or N,N-dimethylanilinium tetra(pentafluorophenyl)borate [II] in combination with Al(Et)₃ no propene polymerization was observed due to the occurrence of reduction of the catalytically active site.     

Solvent- and temperature-dependent functionalisation of enantioenriched aziridines

A highly stereo‐ and regioselective functionalisation of chiral non‐racemic aziridines is reported. By starting from a parent enantioenriched aziridine and finely tuning the reaction conditions, it is possible to address the regio‐ and stereoselectivity of the lithiation/electrophile trapping sequence, thereby allowing the preparation of highly enantioenriched functionalised aziridines. From chiral N‐alkyl trans‐2,3‐diphenylaziridines (S,S)‐ 1 a , b , two differently configured chiral aziridinyllithiums could be generated (trans‐ 1 a , b‐Li in toluene and cis‐ 1 a , b‐Li in THF), thus disclosing a solvent‐dependent reactivity that is useful for the synthesis of chiral tri‐substituted aziridines with different stereochemistry. In contrast, chiral aziridine (S,S)‐ 1 c showed a temperature‐dependent reactivity to give chiral ortho‐lithiated aziridine 1 c‐ ortho ‐Li at ?78 °C and α‐lithiated aziridine 1 c‐α‐Li at 0 °C. Both lithiated intermediates react with electrophiles to give enantioenriched ortho‐ and α‐functionalised aziridines. The reaction of all the lithiated aziridines with carbonyl compounds furnished useful chiral hydroxyalkylated derivatives, the stereochemistry of which was ascertained by X‐ray and NMR spectroscopic analysis. The usefulness of chiral non‐racemic functionalised aziridines has been demonstrated by reductive ring‐opening reactions furnishing chiral amines that bear quaternary stereogenic centres and chiral 1,2‐, 1,3‐ and 1,5‐aminoalcohols. It is remarkable that the solvent‐dependent reactivity observed with (S,S)‐ 1 a , b permits the preparation of both the enantiomers of amines ( 11 and ent‐ 11 ) and 1,2‐aminoalcohols ( 13 and ent‐ 13 ) starting from the same parent aziridine. Interestingly, for the first time, a configurationally stable chiral α‐lithiated aziridine ( 1 c‐α‐Li ) has been generated at 0 °C. In addition, ortho‐hydroxyalkylated aziridines have been easily converted into chiral aminoalkyl phthalans, which are useful building blocks in medicinal chemistry.     

Ring‐Opening Reactions of 3‐Aryl‐1‐benzylaziridine‐2‐carboxylates and Application to the Asymmetric Synthesis of an Amphetamine‐Type Compound

Nucleophilic ring‐opening reactions of 3‐aryl‐1‐benzylaziridine‐2‐carboxylates were examined by using O‐nucleophiles and aromatic C‐nucleophiles. The stereospecificity was found to depend on substrates and conditions used. Configuration inversion at C(3) was observed with O‐nucleophiles as a major reaction path in the ring‐opening reactions of aziridines carrying an electron‐poor aromatic moiety, whereas mixtures containing preferentially the syn‐diastereoisomer were generally obtained when electron‐rich aziridines were used (Tables 1–3). In the reactions of electron‐rich aziridines with C‐nucleophiles, S_N2 reactions yielding anti‐type products were observed (Table 4). Reductive ring‐opening reaction by catalytic hydrogenation of (+)‐trans‐(2S,3R)‐3‐(1,3‐benzodioxol‐5‐yl)aziridine‐2‐carboxylate (+)‐trans‐ 3c afforded the corresponding α‐amino acid derivative, which was smoothly transformed into (+)‐tert‐butyl [(1R)‐2‐(1,3‐benzodioxol‐5‐yl)‐1‐methylethyl]carbamate((+)‐ 14 ) with high retention of optical purity (Scheme 6).     

Stereochemistry and bonding in N-substituted-2-phenyl-3-cyanoaziridines

A series of ten N-alkyl(aralkyl)-2-phenyl-3-cyanoaziridines has been synthesized to continue investigations of the molecular stereochemistry and bonding of functionalized aziridines. Substantial spectroscopic evidence is presented which indicates the presence of stereoselective hyperconjugation between the phenyl and nitrile groups and the aziridine ring. The ¹H and ¹³C nmr chemical shifts are rationalized in terms of the interactions of the substituents on the aziridine ring, and how these interactions vary with the steric bulk of the nitrogen substituents. Various stereoselective coupling constants (¹H-¹H and ¹³C-¹H) are also reported.     

Novel dialkylaminoalkyl- and dialkylaminoalcoxi-benzophenones as photoinitiators of polymerization. I. Photochemical characteristics and radical efficiencies

The behavior of the nonconjugated aminated benzophenones—4-[2′-N,N-(diethylamino)ethoxy]benzophenone (E4), 2-[2′-N,N-(diethylamino)ethoxy]-4-methoxybenzophenone (E2), and 4-N,N-dimethylaminomethylbenzophenone (DM)—as photoinitiators of MMA polymerization has been studied and the results compared with those obtained with the conjugated aminobenzophenone 4-N,N-dimethylamino-4′-isopropyl-benzophenone (CU—MI). Photoreduction behavior of these compounds in various solvents in the presence and absence of MMA has been also examined. The order of the polymerization reaction with respect to monomer and initiator concentrations has been investigated; values of initiation quantum yield (Φ_i), K_p/K^1/2_t and efficiencies of the different radicals have also been determined. Similar polymerization rates (R_p) of methyl methacrylate (MMA) were found when E4 and CU-MI were used as photoinitiators under the same range of absorbed irradiation intensity. This fact results from a compensation between the higher rate of E4 radical production (n-π* transition type) and the greater reactivity of the radicals generated from CU-MI.