Asymmetric synthesis of terminal N-tert-butylsulfinyl aziridines from organoceriums and an alpha-chloroimine

Addition of N-(2-chloroethylidene)- tert-butylsulfinamide to organocerium reagents in DMPU/THF (1:10) at -78 degrees C followed by warming to 25 degrees C provides terminal N-tert-butylsulfinyl aziridines in good yields (63-92%, nine examples) and diastereomeric ratios (85:15- >99:1).     

Straightforward access to enantioenriched 2-allylpiperidine: application to the synthesis of alkaloids

An efficient stereocontrolled preparation of (2R,R(S))-2-allyl-(N-tert-butylsulfinyl)piperidine and its enantiomer is detailed. The sequence requires only two synthetic operations with one-column chromatography and is readily scaled up. The versatility of these chiral building blocks was exemplified by the total or formal synthesis of some natural and unnatural alkaloids.     

Kinetic Study of 1-Substituted Aziridines for Ring-Opening Polymerization Initiated with 3-Hydroxy-1-propane Sulfonic Acid Sultone

Abstract

Kinetics of the cationic polymerization of 1-substituted aziridines, such as 1-methoxycarbonylmethyl aziridine, 1-methoxycarbonylethyl aziridine, and 1-benzyl aziridine, initiated with 3-hydroxy-1-propane sulfonic acid sultone have been investigated, and the results are compared with the results of the polymerization of 1-β-cyanoethyl aziridine. The course of polymerization of 1-methoxycarbonylmethyl aziridine involved a termination reaction due to the reaction between the growing endgroup and the imino group in the polymer chain. On the other hand, the polymerizations of 1-methoxycarbonylethyl aziridine and 1-benzyl aziridine were terminated by a backbiting reaction with the formation of a piper-adinium ring on the polymer end. The propagation and termination constants were obtained at different temperatures, and the enthalpies of activation (ΔH*) and the entropies of activation (ΔS*) for this polymerization were calculated.     

Some reactions of diazomethane with polyfluoroazaolefins

The reactons of some polyfluoroazaolefins with diazomethane are described. Thus 5-H-decafluoro-2-aza-hex-2-(Z)-ene yields 1-trifluoro-methyl-2-fluoro-2-(1,1,2,3,3,3-hexafluoropropyl)-aziridine as the sole isolable product. However, undecafluoro-2-azahex-2(Z)-ene yields not only the corresponding aziridine, 1-trifluoromethyl-2-fluoro-2-(heptafluoropropyl) aziridine, but also 1-trifluoromethyl-5-(heptafluoropropyl)-1,2,3-triazole, and 1-trifluoromethyl-2-fluoromethyl-2-(heptafluoropropyl) aziridine. 5-H-octafluoro-2-azahexa-2(Z)4(Z)-diene yielded the expected aziridine and 1-trifluoromethyl-2-fluoromethyl-2-(1,1,3,3,-tetra-fluoroprop-2-enyl)aziridine. No products were observed as a result of reactions at the C = C bond and no triazole was isolated in this case. Nonafluoroazacyclohex-1-ene gave the corresponding aziridine and a small amount of a compound believed to be 2,2,3,3,4,4,5,5-octafluoro-1,8,9-triazabicyclo [4,3,0] nonadiene i.e. the triazole product.     

The conversion of an aziridine plus an iminium salt to a 1,2-diamine

The conversion of an aziridine to a 1,2-diamine using lithium iodide and an iminium salt is discussed. We have found that when the aziridine is substituted by only alkyl groups, it is the less substituted carbonnitrogen bond that is broken; whereas, when the aziridine is substituted by a phenyl group at either the nitrogen or the carbon, it is the more substituted carbonnitrogen bond that is broken. For a 2,3-disubstituted aziridine, the reaction sequence goes with net retention of stereochemistry.     

Solid‐Phase Parallel Synthesis of Functionalised Medium‐to‐Large Cyclic Peptidomimetics through Three‐Component Coupling Driven by Aziridine Aldehyde Dimers

The first solid‐phase parallel synthesis of macrocyclic peptides using three‐component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9‐ to 18‐membered aziridine‐containing macrocycles, which are then functionalized by nucleophilic opening of the aziridine ring. This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides.     

Heteroatomic derivatives of aziridine. 15. Reaction of 1-(triethylsilyl)- and 1-[2-(trialkylsilyl)ethyl]-aziridines with thiols

The reaction of 1-(triethylsilyl)aziridine with alkanethiols proceeds with splitting out of aziridine and the formation of (alkylthio)triethylsilanes. The reaction of 1-(triethylsilyl)aziridine with 2-mercaptoethanol leads to 2-(triethylsilyloxy)ethanethiol; the same reaction in a closed system leads to [2-(2-aminoethylthiol)ethoxy]triethylsilane. 1-[2-(Trialkylsilyl)ethyl]aziridines react with 2-mercaptoethanol and with mercapto carboyxlic acids with opening of the aziridine ring.See [1] for Communication 14.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 891–893, July, 1988.     

Silylmethyl-substituted aziridine and azetidine as masked 1,3- and 1,4-dipoles for formal [3 + 2] and [4 + 2] cycloaddition reactions

2-tert-Butyldiphenylsilylmethyl-substituted aziridine and the corresponding azetidine reacted efficiently with nitriles and carbonyl substrates to generate imidazoline, oxazolidine, and tetrahydropyrimidine products. The azetidine rearranged efficiently to the pyrrolidine skeleton involving migration of silicon under BF3.Et2O conditions. The tert-butyldiphenylsilylmethyl function, latent to CH2OH group, controlled not only the regioselectivity of aziridine and azetidine cleavage but also the relative stereochemistry of the substituents in the products derived from substituted aziridine.     

Cyclization of monoethanolamine to aziridine over Cs2O–P2O5/SiO2

Several commercially available supports were examined for cyclization of monoethanolamine to aziridine, and SiO₂ was found to yield the best results. The obtained results indicated that selectivity of aziridine was mainly influenced by support. The catalysts were characterized by NH₃-TPD and XRD. It was found that SiO₂ with lower acidity could inhibit the intermolecular condensations, and thus favored the formation of aziridine. The Cs₄P₂O₇ phase was confirmed as the active site in the supported cesium phosphate catalyst. The reaction parameters were also optimized and a yield of 52% aziridine was obtained over 200?h. Thus, a continuous process for the cyclization of monoethanolamine to aziridine has been established.     

1-(Phenylethynyl)aziridine in reactions with amines

The reaction of 1-(phenylethynyl)aziridine with a primary or secondary amine gave 2-benzylimidazoline-2 or N-aminoethyl substituted phenylacetamidine via nucleophilic attack on the aziridine ring. The mechanism of aziridine ring opening by an amine was studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 600–603, May, 1989.     

Synthesis,Physical Properties,and Cytotoxicity of Nitroxyl–Aziridine Hybrid

Nitroxyl–aziridine hybrid, a candidate for a magnetic resonance imaging (MRI) probe and an anticancer drug, was synthesized by aziridine formation reaction of nitroxyl‐introduced aldehyde and guanidinium ylide in good diastereoselectivity. The relative configuration at aziridine C(2) C(3) bond of the major diastereoisomer was determined to be cis by X‐ray crystallographic analysis. Application of chiral guanidinium ylide resulted in the formation of the corresponding optically active aziridine in 84% ee. Reversible one‐electron redox potential and quantitative spin yield of the hybrid were observed in cyclic voltammogram and electron spin resonance, respectively. However, cytotoxicity of the hybrid against cancer cell lines used was not observed.     

Synthesis of optically active 2-alkyl-3,4-iminobutanoic acids. Beta-amino acids containing an aziridine heterocycle

All four stereoisomers of 2-alkyl-3,4-iminobutanoic acid, a novel class of beta-amino acids bearing a chemically versatile aziridine ring, were synthesized starting with aspartic acid. The synthetic strategy involves the introduction of an alkyl group at the beta-position of fully protected optically active aspartic acid followed by the construction of an aziridine ring making use of the alpha-carboxylate and alpha-amino groups. The alpha-carboxylate was reduced to the corresponding alcohol, which was then subjected to cyclization to form an aziridine ring with the N-protected amino group. Removal of the protection groups yielded the target compounds.     

Mechanistic approaches to asymmetric synthesis of aziridines from guanidinium ylides and aryl aldehydes

To approach more realistic mechanisms for asymmetric aziridine synthesis from guanidinium ylides and aryl aldehydes, reactions were systematically carried out by using a variety of p-substituted benzaldehydes under modified conditions. Two kinds of reaction mechanisms controlled by the nature of the p-substituents of aryl aldehydes is proposed for the two-steps aziridine synthesis composed of a C-C bond formation by nucleophilic addition of guanidinium ylides to aryl aldehydes (step 1) and the fragmentation of intermediate adducts to aziridine products by intramolecular nucleophilic substitution (step 2). A S_Ni-like mechanism via cationic-like transition state is proposed for step 2 in the asymmetric synthesis using EDG-substituted benzaldehydes, whereas with EWG-substituted benzaldehydes, a S_N2-like mechanism is proposed. Hammett analysis, based on the diastereomeric ratio in the aziridine products, is consistent with the proposed rate-determining steps in these two mechanisms. A second Hammett analysis, based on the enantiomeric ratio of the aziridine products, clearly reveals the difference in the susceptibilities to the electronic substituents effect between step 1 and step 2.     

Reversible Deactivation Radical Polymerization of Monomers Containing Activated Aziridine Groups

Polymers bearing activated aziridine groups are attractive precursors to α‐substituted‐β‐amino‐functionalized materials due to the enhanced reactivity of the pendant aziridine functionalities toward ring‐opening by nucleophiles. Two aziridine‐containing styrenic monomers, 2‐(4‐vinylphenyl)aziridine (VPA) and N‐mesyl‐2‐(4‐vinylphenyl)aziridine (NMVPA), were polymerized under a variety of reversible deactivation radical polymerization conditions. Low‐catalyst‐concentration atom transfer radical polymerization (LCC‐ATRP) and reversible addition‐fragmentation chain‐transfer (RAFT) polymerization were ineffective at producing well‐defined polymers from VPA due to side reactions between the aziridine functionalities and the agents controlling the polymerizations (catalysts or chain transfer agents). PolyVPA produced under nitroxide‐mediated polymerization (NMP) conditions had narrow molecular weight distribution at low to moderate conversions of monomer, but branched and eventually cross‐linked polymers were formed at higher conversions due to ring‐opening reactions of the aziridine groups. Most of these undesirable side reactions were eliminated by attaching a methanesulfonyl (mesyl) group to the aziridine nitrogen atom, and well‐defined linear homopolymers with targeted molecular weights were realized from NMVPA under RAFT and NMP conditions; however, side reactions between the aziridine groups and the catalyst in LCC‐ATRP still occured and the polymerization was uncontrolled using this technique.

     

Highly enantioselective asymmetric reactions involving zinc ions promoted by chiral aziridine alcohols

Enantiomerically pure, chiral secondary and tertiary aziridine alcohols (including the aziridine analogue of ProPhenol—AziPhenol) have proven to be highly effective catalysts for enantioselective asymmetric reactions in the presence of zinc ions, including arylation of aromatic aldehydes, epoxidation of chalcone and addition of diethylzinc to aldehydes, leading to the desired chiral products in high chemical yields (up to 90%) and with ee’s up to 90%. A higher catalytic activity of Prophenol-type bis(aziridine alcohol) in the aforementioned asymmetric transformations has been demonstrated.     

Effects of the covalent linker groups on the spin transport properties of single nickelocene molecules attached to single-walled carbon nanotubes

The understanding of how the spin moment of a magnetic molecule transfers to a carbon nanotube, when the molecule is attached to it, is crucial for designing novel supramolecular spin devices. Here we explore such an issue by modeling the spin transport of a single-walled carbon nanotube grafted with one nickelocene molecule. In particular we investigate how the electron transport becomes spin-polarized depending on the specific linking group bonding nickelocene to the nanotube. We consider as linkers both aziridine and pyrrolidine rings and the amide group. Our calculations show that, at variance with aziridine, both pyrrolidine and amide, do alter the sp(2) character of the binding site of the nanotube and thus affect the transmission around the Fermi level. However, only aziridine allows transferring the spin polarization of the nickelocene to the nanotube, whose conductance at the Fermi level becomes spin-polarized. This suggests the superiority of aziridine as a linker for grafting magnetic molecules onto carbon nanotubes with efficient spin filtering functionality.     

Induction asymétrique et réaction des α-hydroxy-oximes avec le bromure de phenylmagnésium. Synthéses stéreoselectives d'alcools aziridiniques et d'aza-bicyclo[3.1.0]oxo-2 oxaisothiazolidines-1,2,3

A facile synthesis of aziridine is describe. It is the reaction between Grignard regents and α-hydroxoximes in toluene. The aziridine alchohols are cyclised into 2-oxo-oxathiazolidines. The use of the nuclear Overhauser effect allows the assignment of the relative configurations of these latter compounds and also the configuration of the aziridine alcohols. A proof of the Grignard reagent complex with the alcoolate id given by action of methylmagensium bromide with 2-phenyl 3-methanol azirine. The asymetrie insuction observed is discussed with a transition state involving this complex.     

Aziridines as a protecting and directing group. Stereoselective synthesis of (+)-bromoxone

[reaction: see text] The directing ability of an aziridine group for the epoxidation of adjacent double bonds is demonstrated. The aziridine group is also used to effectively protect a double bond in a cycloenone system for a short synthesis of the title compound.     

Synthesis of silyl aziridines and alpha-amino acylsilanes with silyldibromomethyllithium

The reaction of silyldibromomethyllithium with aromatic imines provides alpha-amino acylsilanes via a bromo aziridine intermediate upon quenching the reaction with water. Alternatively, treatment of the bromo aziridine intermediate with various Grignard reagents or lithium aluminum hydride permits the nucleophilic displacement of the halogen to furnish substituted silyl aziridines.     

Protonation en milieu anhydre d'aziridines,ylures d'azomethine potentiels : Nature des entites formees et etude des divers equilibres

Protonation of aziridines, which are potential azomethine ylides when the equilibrium aziridine?azomethine ylide is established, generally leads to functional iminium salts. A competition between N-protonation of the aziridine and C-protonation of the azomethine ylide may be observed. Factors governing the different acido-basic equilibriums are discussed.