Advances in synthesis and chemistry of aziridines sciencedirect. Metalfree onepot synthesis of 2substituted and 2,3. The article attempts to present, as best as possible, a list of references covering amphetamine synthesis from 1900 2009. Synthesis of nhaziridines from vicinal amino alcohols via the wenker reaction. Furthermore, intramolecular reactions and addition reactions are subdivided with respect to the mechanism of these reactions. 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. Pdf synthesis of chiral 12aminoalkylaziridines via a self. Direct stereospecific synthesis of unprotected nh and nme. First graphene oxide promoted metal free nitrene insertion into olefins in water. A mechanism to explain this novel reaction is proposed. These aziridines undergo a ringopening reaction with a variety of carbon and heteronucleophiles, in good yield, and generally with good regioselectivity.
Synthesis of vicinal haloamines from vinyl aziridines. Nikolova application of aziridines for the synthesis of isoquinoline derivatives 106 the toxicity of aziridine derivatives will depend on its own structure and activity whilst sharing the general characteristics of the aziridine group. First graphene oxide promoted metalfree nitrene insertion. This bonding was first observed in an xray crystal structure. It is a colorless, toxic, volatile liquid that is of significant practical interest. The majority of methods for the preparation of aziridines mimic the highly developed syntheses of epoxides5 or cyclopropanes. Pdf an improved and mild wenker synthesis of aziridines. An amine functional group displaces the adjacent halide in an intramolecular nucleophilic substitution reaction to generate an aziridine. In recent years, our search for new nitrogen transfer reactions has concentrated on aziridine chemistry. Aziridines and epoxides in organic synthesis wiley online books. In continuation of the studies on the synthesis and application of chiral aziridines 1,8,10,29,3233, we used chiral aminoalcohols 1 to convert them into nh aziridines 2 via a modified.
Wulffs group has developed a robust catalytic asymmetric aziridination. Wulffs group has developed a robust catalytic asymmetric aziridination reaction providing. Synthesis of chiral 12aminoalkylaziridines via a self. With the development of the catalytic asymmetric synthesis of trisubstituted aziridines presented here, it will be of interest to investigate the mechanistic di. Aziridine is the organic compounds consisting of the threemembered heterocycle ch22nh. Jan 09, 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.
Molecules free fulltext stereoselective multicomponent. Paudyal, hongyin gao, qinglong xu,1 muhammed yousufuddin,2 deepa devarajan,3 daniel h. Metal free synthesis 6benzylphenanthridines via radical additioncyclization of 2isocyanobiphenyls. Metal free onepot synthesis of morpholine 3a from aziridine 1a. The utility of epoxides, for example, in the enantioselective synthesis of oxygen. Aziridines and epoxides in organic synthesis yudin, andrei k.
Ring expansions of activated aziridines and azetidines. Here, wereportanoperationallysimple,inherentlysafe. Synthesis and reactivity of azapalladacyclobutanes journal. Aziridines, besides the synthesis of pyrroles, have been employed in the synthesis of imidazolines, thiazolines, oxazolines, and 2,3dihydrobenzofurans. A deuteriumlabeling experiment indicates that the oxidative. 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. Rethinking their application and manipulation in synthesis christopher r. Aziridines and epoxides in organic synthesis request pdf. Direct stereospecific synthesis of unprotected nhnme aziridines from olefins. Multiple catalytic methods have been developed to make aziridinesstrained triangular carbonnitrogencarbon rings that function as versatile synthetic intermediates. Direct transformation of epoxides to 1,2diacetates with ac2oboh3 system aziridines are useful intermediates in organic chemistry due to their highly strained ring systems which allow for a wide range of reactivity. Direct stereospecific synthesis of unprotected nhnme. Topics covered include the formation of the aziridine ring as well as the physical and biological properties of aziridines, their polymerization and polymers, and handling and storage.
The three classical methods for the synthesis of aziridines are i addition of a nitrogen moiety across c c bond, ii addition of a carbon moiety across c n bond, and iii cyclization reactions of 2amino alcohols2halo amines. Review recent synthetic applications of chiral aziridines 49 synthesis 2000, no. 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. Montmorillonite k10 as solid acid catalyzes a stereoselective reaction of imines with ethyl diazoacetate to yield cis aziridines. The publication of this book, aziridines and epoxides in organic synthesis, is therefore timely, since there have. 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. Azaheterocyclic compounds are wellknown to have diverse types of biological activity. The optical purity of the obtained cf2substituted aziridines could be further improved by a practical dissolutionfiltration procedure. 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. May 02, 20 general procedures for the synthesis of ndiphenylphosphinyl vinyl aziridines.
Because of the potential for increased efficiency and selectivity, along with the advantages of environmentally benign synthetic procedures. Efficient synthesis of diarylmethylamines via lewis acid catalyzed friedelcrafts reactions of donoracceptor aziridines with n,ndialkylanilines. In addition, oxazolidinones are important heterocyclic compounds showing application as intermediates and chiral auxiliaries in organic synthesis. Most alkenyl boronic acids can be introduced into the reaction as the free boronic acids. 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.
The intramolecular nucleophilic substitution reactions methods ia and ii involve attack of a nucleophilic amino. Pdf a novel approach to the synthesis of optically pure. Synthesis of aziridines by reduction of n tert butanesulfinyl. Application of aziridines for the synthesis of isoquinoline. May 28, 2003 first graphene oxide promoted metal free nitrene insertion into olefins in water. General transformations of aziridines because aziridines are closely related in structure to oxiranes and cyclopropanes, the approaches to their synthesis are very similar. Synthesis and reactivity of azapalladacyclobutanes. The practical stereocontrolled synthesis of vicinal. Direct stereospecific synthesis of unprotected nh and nme aziridines from olefins jawahar l. Synthesis of nsulfonyl aziridines through regioselective. However,apractical,functionalgrouptolerant and environmentally benign direct preparation of nhaziridinesfromstructu rallydiverseolefinshas so far eluded synthetic chemists 2431. Among them, the introduction of fluorine or fluoroalkyl groups into threemembered nheterocycles has emerged as an attractive direction due to the unique fluorine effect in pharmaceuticals and biology. Jan 03, 2014 aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. Aziridines and epoxides in organic synthesis wiley.
The observed excellent yields, regioselectivities and enantioselectivities find no rivals in other organocatalytic aziridine synthesis. Several drugs feature aziridine rings, including mitomycin c, porfiromycin, and azinomycin b carzinophilin. Aziridines article about aziridines by the free dictionary. The in situ generation of dialkyldithiocarbamates provided a simple, user. Falck1 despite the prevalence of the nh aziridine motif in bioactive natural products and the clear. Because of the potential for increased efficiency and selectivity, along with the advantages of environmentally benign synthetic procedures, multicomponent. Angewandte highlights aziridine synthesis new catalysts. 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. Pieczonka, ewelina misztal, michal rachwalski, stanislaw lesniak. Journal of the american chemical society 2009, 1 22, 75287529. The synthesis and applications of nalkenyl aziridines tspace. A photoassisted nicatalyzed reductive crosscoupling between tosylprotected alkyl aziridines and commercially available heteroaryl iodides is reported. Amino alcohols were converted into their hydrogen sulfates with chlorosulfonic acid. Remarkably, both electronrich and electronpoor olefins are converted to aziridines with high efficiency.
This mild and modular method proceeds in the absence of stoichiometric heterogeneous reductants and uses an inexpensive organic photocatalyst to access medicinally valuable. Several synthetic approaches toward 2carboxymethylaziridines based on the di. The parent compound of the aziridines is called aziridine or ethylene imine with molecular formula c 2 h 5 n cas 151564. Besides these three classical approaches to synthesize aziridines, the latter. One promising methodology is the coupling reaction of co2 with aziridines to afford oxazolidinones, which is 100% atomefficient and ecofriendly. 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. Predominantly endiphenylphosphinyl vinyl aziridines are prepared by a reaction of ndiphenylphosphinyl imines with. This chapter presents some of the illustrative and contemporary examples to demonstrate the synthetic diversity and efficiency of the ringexpansion strategies of activated aziridines and azetidines towards a vast array of small to normalsized azaheterocyclic moieties.
Paz with a defined tacticity can be synthesized from aziridines bearing a. Small ring heterocycles, such as epoxides and aziridines, are present in several natural products and are also highly versatile building blocks, frequently involved in the synthesis of numerous bioactive products and pharmaceuticals. A straightforward synthesis of aziridines is reported from electronrich azides, electrondeficient olefins, and triflic acid in cold acetonitrile. Aziridines can be prepared in organic synthesis in several ways. A novel process for the highly stereoselective synthesis of. Direct stereospecific synthesis of unprotected nh and n. Green synthesis of azetidines quinodoze and his colleagues demonstrated an easily practicable method to access. Synthesis of 2carboxymethylaziridine derivatives in the following section, synthesis of 2carboxymethylaziridine derivatives will be dealt with. Synthetic applications of nh aziridine containing compounds shannon marie decker master of science department of chemistry university of toronto. The free electron pair of this nitrogen can either form complexes with metal ions. Most contemporary methods of chiral aziridine preparation have relied on the chiral pool. 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. Alkylative ring opening of nmethylaziridinium ions and a formal. Wenker synthesis is a typical method for synthesis of aziridines in which 2amino alcohols from natural or synthetic amino acids are cyclized by base.
Aziridines are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine nr and two methylene bridges cr 2. Synthetic applications of nh aziridine containing compounds. Despite the prevalence of the nh aziridine motif in bioactive natural products and the clear advantages of this unprotected parent structure over nprotected derivatives as a synthetic building block, no practical methods have emerged for direct synthesis of this compound class from unfunctionalized olefins. Facile and green synthesis of saturated cyclic amines.
Synthesis of nsulfonyl aziridines through regioselective opening of epoxides under solidliquid ptc conditions. 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. The synthesis and applications of nalkenyl aziridines nicholas a. Yudin, aziridines and epoxides in organic synthesis, wileyvch, weinheim 2006. Chiral aziridines are prevalently found in natural products and artificially made bioactive molecules, thus receiving significant attention in the past decades. 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.
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 parent compound is aziridine or ethylene imine, with molecular formula c 2 h 4 nh. A new metal free method is reported for the stereocontrolled opening of vinyl epoxides using boron trichloride or tribromide to yield the corresponding vicinal chlorohydrins and bromohydrins with high regioselectivities and exclusive diastereoselectivity. Nsulfonyl aziridines undergo oxidative addition to palladium0 complexes generated in situ from mixtures of pd2dba3 and 1,10phenanthroline.
This account highlights our efforts toward the synthesis and functionalization of aziridines. Chemistry based on ring opening of aziridines has been widely studied in. Aziridine is the organic compounds consisting of the threemembered heterocycle ch 2 2 nh. The free internet journal for organic chemistry paper archive for organic chemistry arkivoc 2017, part ii, 223234 synthesis of chiral 12aminoalkylaziridines via a selfopening reaction of aziridine adam m.
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. However, the majority require protection of the nitrogen precursor with a sulfonyl group that is subsequently inconvenient to remove. Tetrahedron tetrahedron 55 1999 63876394 pergamon synthesis of nsulfonyl aziridines through regioselective opening of epoxides under solidliqui. Chemistry and applications deals with the chemistry and applications of ethylenimine and other aziridines. Advances in nitrogen transfer reactions involving aziridines. Pharmaceutically active 2 and 2,3disubstituted morpholines. Stereoselective synthesis of 2,3di and 2,2,3trisubstituted aziridines in good yields and excellent diastereoselectivities are achieved through azadarzens reactions of a range of tert. Synthesis and reactivity of 2 carboxymethylaziridine. Recent synthetic applications of chiral aziridines william mccoull,a franklin a.
Heterogeneous catalysis for oxazolidinone synthesis from. Catalytic asymmetric synthesis of trisubstituted aziridines. The practical stereocontrolled synthesis of vicinal halohydrins and haloamines from vinyl epoxides and vinyl aziridines lukasz j. A reaction of a chiral aldimine derived from phenylalaninal proceeded with high diastereoselectivity. Discovering effective new methods for the synthesis of aziridines and epoxides, as well as developing novel transformations of these heterocycles, has been an extremely active area of research in recent years. Several routes have been developed for the syntheses of aziridines aziridination. Synthesis of chiral 12aminoalkylaziridines via a selfopening. In the course of our research, we have investigated the electrochemical aziridination of olefins, the acidcatalyzed ring opening of aziridines, and the development of transition metal mediated. Diastereoselective desymmetrization of pquinamines. Ringopening reactions of nonactivated aziridines catalyzed. Pdf aziridines are important precursors for the synthesis of various. The resulting pale yellow solution was then stirred at 0 c for 30.
Quinolone, and naphthaleneannulated 2aminothiazoles under ligand free conditions. The class of aziridines are of broader interest in medicinal chemistry. Aziridines are a group of organic compounds sharing the aziridine functional group which is a three membered heterocycle with one amine group and two methylene groups. The resulting azapalladacyclobutane complexes undergo intramolecular carbopalladation in the presence of copperi iodide to afford azapalladabicyclo3. Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. In addition, it also allows the synthesis of enantioenriched products by using easily accessible chiral nonracemic epoxides and aziridines. The synthesis and applications of nalkenyl aziridines. Aziridines are important precursors for the synthesis of various nitrogencontaining bioactive molecules, such as heterocycles, alkaloids and amino acids. Asymmetric synthesis of cf2functionalized aziridines by. A novel process for the highly stereoselective synthesis of isa247 voclosporin and close analogues. 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 to ringstrain, building blocks in organic synthesis, and its biological.
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