Selected examples for the synthesis of aziridines from alkenes r2 r1 r2 n x r1 r2 r1 xn singlet nitrene triplet nitrene xn h r2 r1 h x n h r2 r1 h x n h r2 r1 h x n j. Constricted heterocycles can behave as intermediates in a synthesis and are decidedly susceptible to ring expansion and opening processes figure 4. Synthesis and biological activity of novel epothilone aziridines. A pd and norbornenecatalyzed domino procedure has been developed to synthesize indoline compounds. Synthesis and biological activity of novel epothilone. Nonactivated aziridines as building blocks for the synthesis of aza. It is used industrially for the synthesis of aziridine itself. Butler september 16, 2004 introduction aziridines 1 have been synthetic targets as well as useful building blocks in synthesis since gabriels 1888 discovery of the smallest nitrogen containing heterocycle. Aziridines are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine nr and two methylene bridges cr 2.
Synthesis and ring openings of cinnamatederived nunfunctionalised aziridines alanarmstrong andalexandraferguson full research paper open access address. Pdf asymmetric synthesis of 22pyridylaziridines from. A mechanism to explain this novel reaction is proposed. Development of aziridines for biological purposes is merely one rationale bolstering enthusiasm for their capabilities, as delineated earlier. The first organocatalytic asymmetric nucleophilic addition of arylpyrazoles to 2hazirines and kinetic resolution of racemic 2hazirines have been realized. Furthermore, intramolecular reactions and addition reactions are subdivided with respect to the mechanism of these reactions. Aziridines, organic synthesis, green chemistry, olefins, chloraminet, imine. The transformation is scalable and tolerates a range of functional groups. Synthesis of aziridines aziridines and epoxides in. Department of chemistry, university of central florida abstract.
Chiral aziridines were obtained with up to 98% yields and up to 99. Synthesis and evaluation of biological activities of. Encouraged by this promising result, we next examined the scope of the reaction by using the same anion and ndpp imines derived from 4bromo and 4fluorobenzaldehyde, furfural and 2,2dimethylpropionaldehyde. The wenker synthesis is an organic reaction converting a beta amino alcohol to an aziridine with the help of sulfuric acid. To our knowledge, this was the first reported direct synthesis of a vinyl aziridine bearing a phosphorus group on nitrogen.
Readily accessed allylic hydroxylamine esters undergo copper hydridecatalyzed intramolecular hydroamination with a high degree of regio and enantiocontrol to. Organocatalyzed nucleophilic addition of pyrazoles to 2h. Pdf asymmetric synthesis of 22pyridylaziridines from 2. Bypassing the inertness of aziridineco2 systems to access 5aryl. Epoxycyclohexane was synthesized using a twostep approach. The catalytic system, which operates at room temperature under neutral and nonoxidative conditions, is applicable to both aromatic and electrondeficient olefins and enables the synthesis of ncarbonyl aziridines in high yields with excellent. The reaction of the budam imine 48 scheme 1 and ethyl diazoacetate 12 with. Synthesis of aziridines catalysed by pi263fa328vl437v 19 enzyme. A series of aziridines in reaction with isocyanates and isothiocyanates to obtain urea and thiourea derivatives were used. A reaction of a chiral aldimine derived from phenylalaninal proceeded with high diastereoselectivity. Aziridine is a saturated organic heteromonocyclic parent, a member of aziridines and an azacycloalkane.
To the best of our knowledge the mechanism of iron porphyrincatalysed aziridination. The azaaddition for vicinal diamines using a variety of alkyl, aryl and mesobicyclic aziridines with a tosylprotecting group and aromatic aminenucleophilic moieties bearing electronic substituents in the aryl ring were investigated scheme 27. Aziridination of alkenes promoted by iron or ruthenium. Synthesis of aziridines by reduction of n tert butanesulfinyl. Asymmetric synthesis of cf2functionalized aziridines by combined strong bronsted acid catalysis a diastereo and enantioselective approach to access chiral cf2functionalized aziridines from difluorodiazoethyl phenyl sulfone phso2cf2chn2 and in situformed aldimines is described. A onepot method for the synthesis of indolinefused pyrrolidines 325 scheme 107 by a domino ringopening cyclization of activated aziridines 324 with indoles 323 having substituents at c3. The final semisynthetic route involves a formal doubleinversion of stereochemistry at both the c12 and c positions. Two alternative and complementary onepot procedures for the direct transformation of 2amino alcohols to ntosyl aziridines are presented. This is illustrated in the enantio and diastereoselective synthesis of the cis and transisomers of the nboc aziridines 17a shown in scheme 4. Addition of nitrene equivalents to dienes the addition of a nitrene equivalent to a conjugated diene is a traditional method for direct synthesis of aziridines. Rethinking their application and manipulation in synthesis christopher r. Synthesis of 2carboxymethyl aziridines is effectuated via functional group transformations of compounds derived from the chiral pool or starting from 2formylaziridines. Filling a gap in the literature, this clearly structured book presents the much. Synthesis of 2carboxymethylaziridine derivatives in the following section, synthesis of 2carboxymethylaziridine derivatives will be dealt with.
Catalytic asymmetric synthesis of trisubstituted aziridines. Synthesis of aziridines aziridines and epoxides in organic. Pdf aziridines are important precursors for the synthesis of various nitrogen containing bioactive molecules, such as heterocycles, alkaloids and. Consequently, other routes to these fundamentally interesting molecules must be devised. Nitrene 2 was generated by photolysis of the methoxycarbonyl azide 1, and the reaction of 2 with e or. Synthesis of 2aminomethyl aziridines and their microwaveassisted ring opening to 1,2,3triaminopropanes as novel antimalarial pharmacophores. Scheme 14 while a great deal of consideration has been given to the synthesis of cvinyl aziridines. Mar 29, 2021 a coiibased system has been developed for enantioselective radical aziridination of alkenes using the carbonyl azide trocn 3 as the nitrogen source. A general strategy for the synthesis of enantiomerically pure. The parent compound is aziridine or ethylene imine, with molecular formula c 2 h 4 nh. Dec 25, 2017 in the present paper, we report the synthesis and evaluation of in vitro antimicrobial activities of aziridinethiourea derivatives. The conventional wenker synthesis of aziridines from vicinal amino alcohols has been modified by employing mild. General procedures for the synthesis of ndiphenylphosphinyl vinyl aziridines method a.
A twostep synthesis for preparing epoxycyclohexane john l. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. Department of chemistry, imperial college london, south kensington, london, sw7 2az, u. Synthesis of indolines via a palladiumnorbornenecatalyzed. Pdf cobaltcatalyzed aziridination with diphenylphosphoryl. Beilstein archives asymmetric synthesis of cf2aziridines. Mar 27, 2015 in addition, we have expanded this concept to the synthesis of enantiomerically pure, terminal alkyl aziridines. Asymmetric synthesis of cf2functionalized aziridines by. Synthesis of aziridines from epoxides the simplest and oldest preparation of aziridines is the ring closure of a.
Synthesis of 2aminomethyl aziridines and their microwaveassisted ring opening to 1,2,3triaminopropanes as novel antimalarial pharmacophores matthias dhooghe ugent, sara kenis ugent, karel vervisch ugent, carmen lategan, peter smith, kelly chibale and. Application of aziridines for the synthesis of isoquinoline. Ringopening of cycloalkane epoxides and aziridines with. Aziridines and epoxides in organic synthesis wiley online books. This protocol offers a direct route for the synthesis of alkylsubstituted chiral aziridines from achiral starting materials. The new method allows direct conversion of alkenes into nphosphorylated aziridines. The reaction of ntosyl imines with in situ generated iodomethyllithium, with a simple and rapid experimental protocol, allows an efficient and general synthesis of aziridines. Synthetic applications of nh aziridine containing compounds. The synthesis and applications of nalkenyl aziridines.
The original wenker synthesis of aziridine itself takes place in two steps. The cytotoxicity of the aminoalkylated aziridines with heteroorganic. Multicomponent catalytic asymmetric synthesis of trans. All aziridine analogues were tested for effects on tubulin binding polymerization and cytotoxicity. School of chemistry, university of reading, reading rg6 6ad, uk. Studies have been made on the possible synthesis of 1arylethynyl aziridines by oxidative condensation of phenylacetylene with aziridine and by alkylation of aziridine with 1halo2arylacetylenes. Feb 20, 2006 aziridines and epoxides are among the most widely used intermediates in organic synthesis, acting as precursors to complex molecules due to the strains incorporated in their skeletons. The observed excellent yields, regioselectivities and enantioselectivities find no rivals in other organocatalytic aziridine synthesis. The intramolecular nucleophilic substitution reactions methods ia and ii involve attack of a nucleophilic amino. Al2o3 nanoparticles, opening of the epoxide by nan3, and cyclization of the azidoalcohol by ph3p followed by condensation of the resulting aziridines with formalin and secondary amines. Reaction of chiral alphachloro ntertbutanesulfinyl ketimines with grignard reagents afforded new chiral nsulfinyl 2,2disubstituted aziridines in good to excellent diastereomeric ratio dr up to 98. Jun 20, 2017 one of the aziridines is closely related to a compound used in the synthesis of an advanced intermediate en route to zanamivir, an antiviral agent. The stereoselectivity obtained in the grignard addition is.
A mild, convenient protocol for the synthesis of cis aziridines employs a catalytic amount of bronsted acid. Widening the usefulness of epoxides and aziridines in synthesis. A convenient and versatile synthesis is desirable in order to permit studies of this important biologically active heterocyclic system. In spite of the fact that a number of methods are available for the preparation of aziridines, general synthetic routes leading to 1,2disubstituted aziridines remained laborious in most cases 26. Aziridines, besides the synthesis of pyrroles, have been employed in the synthesis of imidazolines, thiazolines, oxazolines, and 2,3dihydrobenzofurans. Aziridines are organic compounds containing the aziridine functional group, a threemembered. Abstract synthesis of imidazolines from aziridines by michael robert kuszpit the majority of the work in this thesis presents a new method to syntheisize imidazolines. Several drugs feature aziridine rings, including mitomycin c, porfiromycin, and azinomycin b carzinophilin. Introduction we have recently reported the development of the. Jan 26, 2009 selected examples for the synthesis of aziridines from alkenes r2 r1 r2 n x r1 r2 r1 xn singlet nitrene triplet nitrene xn h r2 r1 h x n h r2 r1 h x n h r2 r1 h x n j.
This reaction provides efficient access to indolines by employing aryl iodides with aziridines as new electrophiles. Disappointingly, the yields of aziridines 25 obtained from. However, an extra synthetic step may be required to remove the nfunctionality, which is often difficult and low yielding 1115. An updated library on the synthesis of aziridines bentham science. Less hindered aziridines can be obtained in high yields by tosylation and in situ cyclization effected by potassium hydroxide in waterdichloromethane. Catalytic preparation of aziridines with an iron lewis acid the. Furthermore, one of the aziridines was converted into a piperidineazepine fused derivative.
The results indicate that the aziridine moiety is a viable. Cuhcatalyzed regioselective intramolecular hydroamination. A general strategy for the synthesis of enantiomerically. This salt is then reacted with sodium hydroxide in the second step forming aziridine. Direct 52 100 synthesis of nphosphorussubstituted aziridines from alkenes. Aziridines and epoxides are among the most widely used intermediates in organic synthesis, acting as precursors to complex molecules due to the strains incorporated in their skeletons. Several synthetic approaches toward 2carboxymethyl aziridines based on the di. Azaheterocyclic compounds are wellknown to have diverse types of biological activity. Bjoc asymmetric synthesis of cf2functionalized aziridines. Cyclohexene was used as a starting reagent and treated with nbromosuccinamide nbs in an aqueous solution and liquidliquid extraction was performed at this stage.
Advances in synthesis and chemistry of aziridines sciencedirect. Amino alcohols were converted into their hydrogen sulfates with chlorosulfonic acid. Ring strain and its exploitation in organic synthesis. Article views are the countercompliant sum of full text article downloads since november 2008 both pdf and html across all institutions. Download free pdf asymmetric synthesis of 22pyridyl aziridines from 2pyridineimines bearing stereogenic nalkyl substituents and regioselective opening the aziridine ring cheminform, 2007.
The base abstracts an amine proton enabling it to displace the sulfate group. Bypassing the inertness of aziridineco2 systems to access 5aryl2 oxazolidinones. Among them, azacyclopropanes, commonly referred as aziridines, occupy a prominent place in synthetic organic and medicinal chemistry due to its occurrence in natural resources, complexity involved in synthesis due. Synthesis and reactivity of 2 carboxymethylaziridine. Synthesis of 2aminomethylaziridines and their microwave. Feb 17, 2020 open access preprint on asymmetric synthesis of cf2 aziridines enabled by combined strong bronsted acid catalysis a diastereo and enantioselective approach to access chiral cf2functionalized aziridines from phenylsulfone difluorodiazoethane phso2cf2chn2 and insitu formed aldimines is described.
A second subsection dedicated to the synthesis of optically pure c2,3disubstituted naryl and nh cis aziridines was achieved by means of a chiral binolderived ntriflylphosphoramide bronsted acid catalyst. A nucleophileinduced ring opening of aziridines under catalystfree and solventless conditions was reported by huang et al. Meanwhile, simply changing the ratio of reactants, optically active 2hazirine. This report details a general and enantioselective means for the synthesis of alkylsubstituted aziridines. Applications of vinyl aziridines in synthesis 14 1. Multicomponent catalytic asymmetric synthesis of transaziridines. Jan 01, 2019 aziridines, besides the synthesis of pyrroles, have been employed in the synthesis of imidazolines, thiazolines, oxazolines, and 2,3dihydrobenzofurans. Pdf synthesis of pentaaminechlorocobalt iii chloride. However, an efficient and stereoselective approach has been developed by an extension of.
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