A novel strategy involving visiblelightinduced functionalization of alkenes for the synthesis of substituted aziridines was developed. Application of aziridines for the synthesis of isoquinoline. Wulffs group has developed a robust catalytic asymmetric aziridination reaction providing. Darzens reaction of cyclic imines with halogenated ketones catalyzed by bifunctional phosphonium salt. Enantioselective synthesis of diaryl aziridines using. Ozdemir do gan september 2010, 74 pages a systematic study was carried out for the synthesis of aziridine 2phosphonates by using two methods. We have previously reported on our studies on the use of activity. Chapter 1 gives a brief introduction to the synthesis and ring opening reactions of aziridines. Although ring closure itself is quite facile, the synthesis of the required precursors can be problematic. A reaction of a chiral aldimine derived from phenylalaninal proceeded with high diastereoselectivity. S1 supporting information asymmetric synthesis of trisubstituted aziridines via azadarzens reaction of chiral sulfinimines toni moragas, ian churcher.
This mild and modular method proceeds in the absence of stoichiometric heterogeneous reductants and uses an inexpensive organic photocatalyst to access medicinally valuable. The reaction proceeds in onepot via a highly diastereoselective cyclisation of an amino gemdiiodide intermediate. Jessing 1 n r activated aziridines r co2r, so2r and cor nonactivated aziridines r h, alkyl and aryl ho nh2 o so nh 2 o o n h aziridines can be synthesized in numerous ways including sn2 displacement, 14 addition, addition of carbenes, electrophiles, nitrenes and reduction h. Synthesis of novel ironcomplexes and study of their catalytic activity in aziridination, cyclopropanation and amination. Pharmaceutically active 2 and 2,3disubstituted morpholines. General procedures for the synthesis of ndiphenylphosphinyl vinyl aziridines. Nitrogen heterocycles aziridines cycloaddition carbon dioxide fixation zwitterions 1,3dipoles chemistry based on ring opening of aziridines has been widely studied in organic synthesis. A straightforward synthesis of aziridines is reported from electronrich azides, electrondeficient olefins, and triflic acid in cold acetonitrile. Synthesis of ferrocenyl substituted aziridines zeytinci, serhat m. The wenker synthesis is an organic reaction converting a beta amino alcohol to an aziridine with the help of sulfuric acid. Two alternative and complementary onepot procedures for the direct transformation of 2amino alcohols to ntosyl aziridines are presented. Chapter 2 gives a brief introduction to flow chemistry, and describes the synthesis of aziridines from 1,2amino alcohols, as well as their subsequent ring. Alkene functionalization for the stereospecific synthesis of.
Wenker synthesis is a typical method for synthesis of aziridines in which 2amino alcohols from natural or synthetic amino acids are cyclized by base. First method is the classical gabrielcromwell reaction and the. It is noteworthy that, when reacted with polymersupported pph 3, the diobenzyldiazidodiol entry 3 led to a 11 mixture of the expected nh bisaziridine 2a and of the furan 14. Furthermore, intramolecular reactions and addition reactions are subdivided with respect to the mechanism of these reactions. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. Synthesis of aziridines from epoxides the simplest and oldest preparation of aziridines is the ring closure of a. 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 catalyst and analogues thereof were prepared through an expeditious and efficient synthetic route featuring a double nucleophilic substitution and shi epoxidation. Glaxosmithkline, gunnels wood road, stevenage, sg1 2ny, u. This work describes catalytic and asymmetric aziridinations 15 examples, 9598% ee of benzyl bromide and imines via the imino coreychaykovsky reaction using thiolan2yldiarylmethanol benzyl ether as an organocatalyst. Pdf a novel approach to the synthesis of optically pure 12aminoalkyl aziridines via a nucleophilic ringopening reaction of aziridine is. The asymmetric synthesis of terminal aziridines by methylene. With the development of the catalytic asymmetric synthesis of trisubstituted aziridines presented here, it will be of interest to investigate the mechanistic di.
Aziridines are important precursors for the synthesis of various nitrogencontaining bioactive molecules, such as heterocycles, alkaloids and amino acids. Synthesis and reactions of aziridines via batch and flow. 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. Aziridines and epoxides in organic synthesis request pdf. A mechanism to explain this novel reaction is proposed. Synthesis and reactions of aziridines via batch and flow processes. A general strategy for the synthesis of enantiomerically pure.
Fluoroamines by lewis base catalyzed hydrofluorination of aziridines julia a. The original wenker synthesis of aziridine itself takes place in two steps. However, an efficient and stereoselective approach has been developed by an extension of. Synthesis of aziridine 2phosphonates and their biological activities babiz, hakan m. Synthesis of aziridines by reduction of n tert butanesulfinyl. Mar 27, 2015 in addition, we have expanded this concept to the synthesis of enantiomerically pure, terminal alkyl aziridines. Catalytic asymmetric synthesis of trisubstituted aziridines. Recent advances in the stereoselective synthesis of aziridines. Apr 23, 2020 fluorinated aziridines are very important structural motifs, but methods access to such structures are still very rare. The base abstracts an amine proton enabling it to displace the sulfate group. A new route for the synthesis of 2,3 aziridines is described. An amine functional group displaces the adjacent halide in an intramolecular nucleophilic substitution reaction to generate an aziridine.
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. Synthesis of aziridines from alkenes and aryl azides with. Amino alcohols were converted into their hydrogen sulfates with chlorosulfonic acid. Most contemporary methods of chiral aziridine preparation have relied on the chiral pool. Jun 07, 20 the asymmetric synthesis of terminal aziridines by methylene transfer from sulfonium ylides to imines.
Recent synthetic applications of chiral aziridines william mccoull,a franklin a. Beilstein journal of organic chemistry 2014, 10, 12821289. Pdf synthesis of new bicyclic aziridines containing. Aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. Request pdf aziridines and epoxides in organic synthesis introductionpreparation of aziridine2carboxylates and aziridine2phosphonates preparation of aziridine2carboxylates cyclization of. This photochemical transformation features synthetic. Alkene functionalization for the stereospecific synthesis. A new route for the synthesis of 2,3aziridines is described. Doyle department of chemistry, princeton university frick chemical laboratory, princeton, nj 08544 usa email.
Several synthetic approaches toward 2carboxymethylaziridines based on the di. Aziridines can be prepared in organic synthesis in several ways. The cyclization of an amino alcohol is called a wenker synthesis 1935 and that of a haloamine the gabriel ethylenimine method 1888 nitrene addition. General characteristics epoxides can be converted into aziridines by nucleophilic attack of azide ion, the staudinger reaction, and aziridine ring formation with. Pergamon 0040403994017255 tetrahedron letters, vol. Metalfree onepot synthesis of morpholine 3a from aziridine 1a. Aziridine is an organic compound consisting of the threemembered heterocycle ch 2 2 nh. Pdf aziridines are important precursors for the synthesis of various nitrogen containing bioactive molecules, such as heterocycles, alkaloids. The observed excellent yields, regioselectivities and enantioselectivities find no rivals in other organocatalytic aziridine synthesis. Remarkably, both electronrich and electronpoor olefins are converted to aziridines with high efficiency. Rethinking their application and manipulation in synthesis christopher r. A straightforward synthesis of aziridines is reported from electronrich azides, electrondeficient olefins, and. Less hindered aziridines can be obtained in high yields by tosylation and in situ cyclization effected by potassium hydroxide in waterdichloromethane.
The reaction proceeds well with various silyl dienol ethers and vinyl aziridines, and enables the efficient synthesis of highly functionalized azepines in an enantioselective manner with. Nitrene addition to alkenes is a well established method for the synthesis of aziridines. Lewis acidcatalyzed synthesis of aziridines the journal of. The synthesis of ntosylaziridines 7 was accomplished by basemediated cyclization of bistosylates 6 of 2amino alcohols 5 in water and dichloromethane in equal amounts scheme 1. A general strategy for the synthesis of enantiomerically. Jan 03, 2014 aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. Review recent synthetic applications of chiral aziridines 49 synthesis 2000, no. Synthesis of cyclophellitol, cyclophellitol aziridine, and. In addition, we have expanded this concept to the synthesis of enantiomerically pure, terminal alkyl aziridines. Aug 14, 2014 cyclitol epoxides and aziridines are potent and selective irreversible inhibitors of retaining glycosidases. Reduction of aamino acids also provides bamino alcohols and therefore could lends access to aziridines. The synthesis of n tosylaziridines 7 was accomplished by basemediated cyclization of bistosylates 6 of 2amino alcohols 5 in water and dichloromethane in equal amounts scheme 1.
Dec 14, 2016 a new synthetic application of vinyl aziridines as n. The readily prepared nprotected 1aminopyridinium salts were used for the generation of ncentered radicals. Metalfree onepot synthesis of 2substituted and 2,3. Synthesis and reactivity of 2 carboxymethylaziridine. 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. This thesis describes the synthesis and ring opening reactions of aziridines performed under batch as well as continuous flow conditions. Asymmetric synthesis of trisubstituted aziridines via aza. In particular, inclusion of an adjacent vinyl group provides the kinetic impetus to drive. A new synthetic application of vinyl aziridines as n.
The simplest and oldest preparation of aziridines is the ring closure of a. Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. Fluorinated aziridines are very important structural motifs, but methods access to such structures are still very rare. Studies have been made on the possible synthesis of 1 arylethynylaziridines by oxidative condensation of phenylacetylene with aziridine and by alkylation of aziridine with 1halo2arylacetylenes. Bicyclic aziridines, derivatives of 2,2,6,6tetramethyl4piperidone triacetoneamine, are synthesized, which by acids treatment undergo the nc1 or nc2 bonds cleavage to form the corresponding pyrrolines, pyrrolidines, and piperidines. The synthesis and applications of nalkenyl aziridines. It is used industrially for the synthesis of aziridine itself. This salt is then reacted with sodium hydroxide in the second step forming aziridine. Recent advances regarding the synthetic chemistry of fluorinated aziridines and azetidines are presented in this chapter. Synthesis and nucleophilic opening of a new symmetric bis.
Cyclitol epoxides and aziridines are potent and selective irreversible inhibitors of retaining glycosidases. Catalytic asymmetric synthesis of alkynyl aziridines. Synthetic applications of nh aziridine containing compounds shannon marie decker master of science department of chemistry university of toronto 2010 abstract unprotected nh aziridine aldehydes are surprisingly stable compounds which can undergo reactions in the absence of protecting groups. Jessing 1 n r activated aziridines r co2r, so2r and cor nonactivated aziridines r h, alkyl and aryl ho nh2 o so nh 2 o o n h aziridines can be synthesized in numerous ways including sn2 displacement, 14 addition. Synthesis of fourmembered heterocycles cycloaddition 6 cycloaddition is the union of two.
Aziridines are valuable strained small heterocycles of interest in preparative organic synthesis. Lewis acidcatalyzed synthesis of aziridines the journal. Pdf synthesis of chiral 12aminoalkylaziridines via a self. Aziridines ethylene imines are important building blocks in organic synthesis, because they allow for convenient access to amines, amino alcohols, diamines, and other useful nitrogencontaining molecules. Aziridines continue to provide both structural fascination,1 and important synthetic intermediates for wide ranging applications in chemical synthesis. The reaction of methyl 2,3dibromohexadecanoate ii with ammonia at 0 c gave methyl 2bromohexadec2enoate iii, ca. The sulfates were cyclized with sodium hydroxide, and even with nonnucleophilic sodium carbonate. Synthesis of chiral n phosphoryl aziridines through enantioselective aziridination of alkenes with phosphoryl azide via coiibased metalloradical catalysis. The synthesis and applications of nalkenyl aziridines nicholas a. Afagh master of science department of chemistry university of toronto 2010 abstract nalkenyl aziridines are a unique class of molecules that do not behave as typical enamines as a result of the inability of the nitrogen atom lonepair of electrons to delocalize. Synthetic applications of nh aziridine containing compounds.
A second subsection dedicated to the synthesis of optically pure c2,3disubstituted naryl and nh cisaziridines was achieved by means of a chiral binolderived ntriflylphosphoramide bronsted acid catalyst. Jessing 1 n r activated aziridines r co2r, so2r and cor nonactivated aziridines r h, alkyl and aryl ho nh2 o so nh 2 o o n h aziridines can be synthesized in numerous ways including sn2 displacement, 14 addition, addition of carbenes, electrophiles, nitrenes and reduction. Synthesis of aziridines baminoalcohols to aziridines 8 to aid the formation of a strong po bond, the triphenylphosphine serves to convert the oh group into a good leaving group that is displaced intramolecularly by the amino group. 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. The intramolecular nucleophilic substitution reactions methods ia and ii involve attack of a nucleophilic amino. A photoassisted nicatalyzed reductive crosscoupling between tosylprotected alkyl aziridines and commercially available heteroaryl iodides is reported. Direct stereospecific synthesis of unprotected nhnme. Compound iii, on further treatment with ammonia at 25 c, gave methyl 2aminohexadec2enoate iv, ca. Facile synthesis of aziridines from imines and diazoesters or aldehydes, amines, and diazoesters using a catalytic amount of lanthanide triflate. Stockman school of chemistry, university of nottingham, nottingham, ng7 2rd, u. Synthesis of 2carboxymethylaziridine derivatives in the following section, synthesis of 2carboxymethylaziridine derivatives will be dealt with.
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