Ringopening reactions of nonactivated aziridines catalyzed. Angewandte highlights aziridine synthesis new catalysts. The practical stereocontrolled synthesis of vicinal halohydrins and haloamines from vinyl epoxides and vinyl aziridines lukasz j. Direct stereospecific synthesis of unprotected nh and nme. Pdf an improved and mild wenker synthesis of aziridines. The publication of this book, aziridines and epoxides in organic synthesis, is therefore timely, since there have. Here, wereportanoperationallysimple,inherentlysafe.
Pharmaceutically active 2 and 2,3disubstituted morpholines. Because of the potential for increased efficiency and selectivity, along with the advantages of environmentally benign synthetic procedures. Asymmetric synthesis of cf2functionalized aziridines by. The optical purity of the obtained cf2substituted aziridines could be further improved by a practical dissolutionfiltration procedure. Aziridines and epoxides in organic synthesis request pdf. 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 mechanism to explain this novel reaction is proposed. Chemistry and applications deals with the chemistry and applications of ethylenimine and other aziridines.
However, the majority require protection of the nitrogen precursor with a sulfonyl group that is subsequently inconvenient to remove. The intramolecular nucleophilic substitution reactions methods ia and ii involve attack of a nucleophilic amino. The synthesis and applications of nalkenyl aziridines nicholas a. The practical stereocontrolled synthesis of vicinal. Advances in synthesis and chemistry of aziridines sciencedirect. Because of the potential for increased efficiency and selectivity, along with the advantages of environmentally benign synthetic procedures, multicomponent. 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. Metal free onepot synthesis of morpholine 3a from aziridine 1a. 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. Heterogeneous catalysis for oxazolidinone synthesis from. Metal free synthesis 6benzylphenanthridines via radical additioncyclization of 2isocyanobiphenyls.
Chemistry based on ring opening of aziridines has been widely studied in. Predominantly endiphenylphosphinyl vinyl aziridines are prepared by a reaction of ndiphenylphosphinyl imines with. 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. 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. Pdf synthesis of chiral 12aminoalkylaziridines via a self. Falck1 despite the prevalence of the nh aziridine motif in bioactive natural products and the clear. Paudyal, hongyin gao, qinglong xu,1 muhammed yousufuddin,2 deepa devarajan,3 daniel h. Synthesis of nhaziridines from vicinal amino alcohols via the wenker reaction. Aziridines and epoxides in organic synthesis wiley online books. 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.
The parent compound is aziridine or ethylene imine, with molecular formula c 2 h 4 nh. Direct stereospecific synthesis of unprotected nhnme. 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. Synthesis and reactivity of 2 carboxymethylaziridine. An amine functional group displaces the adjacent halide in an intramolecular nucleophilic substitution reaction to generate an aziridine. 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. Wulffs group has developed a robust catalytic asymmetric aziridination reaction providing. With the development of the catalytic asymmetric synthesis of trisubstituted aziridines presented here, it will be of interest to investigate the mechanistic di. Aziridines and epoxides in organic synthesis yudin, andrei k. Synthesis of chiral 12aminoalkylaziridines via a selfopening. Synthesis and reactivity of azapalladacyclobutanes journal.
Alkylative ring opening of nmethylaziridinium ions and a formal. The observed excellent yields, regioselectivities and enantioselectivities find no rivals in other organocatalytic aziridine synthesis. 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. 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. 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. One promising methodology is the coupling reaction of co2 with aziridines to afford oxazolidinones, which is 100% atomefficient and ecofriendly. Metalfree onepot synthesis of 2substituted and 2,3. Aziridines, besides the synthesis of pyrroles, have been employed in the synthesis of imidazolines, thiazolines, oxazolines, and 2,3dihydrobenzofurans. 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. 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 article attempts to present, as best as possible, a list of references covering amphetamine synthesis from 1900 2009. Diastereoselective desymmetrization of pquinamines. 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. The majority of methods for the preparation of aziridines mimic the highly developed syntheses of epoxides5 or cyclopropanes.
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. 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. A straightforward synthesis of aziridines is reported from electronrich azides, electrondeficient olefins, and triflic acid in cold acetonitrile. Quinolone, and naphthaleneannulated 2aminothiazoles under ligand free conditions. Azaheterocyclic compounds are wellknown to have diverse types of biological activity. 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. 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.
The free electron pair of this nitrogen can either form complexes with metal ions. 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. In addition, it also allows the synthesis of enantioenriched products by using easily accessible chiral nonracemic epoxides and aziridines. Recent synthetic applications of chiral aziridines william mccoull,a franklin a. Synthesis of 2carboxymethylaziridine derivatives in the following section, synthesis of 2carboxymethylaziridine derivatives will be dealt with. 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. Furthermore, intramolecular reactions and addition reactions are subdivided with respect to the mechanism of these reactions. Application of aziridines for the synthesis of isoquinoline. Pdf a novel approach to the synthesis of optically pure. The resulting pale yellow solution was then stirred at 0 c for 30. Synthesis of aziridines by reduction of n tert butanesulfinyl. Direct stereospecific synthesis of unprotected nhnme aziridines from olefins. A reaction of a chiral aldimine derived from phenylalaninal proceeded with high diastereoselectivity.
Jan 03, 2014 aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. This mild and modular method proceeds in the absence of stoichiometric heterogeneous reductants and uses an inexpensive organic photocatalyst to access medicinally valuable. The parent compound of the aziridines is called aziridine or ethylene imine with molecular formula c 2 h 5 n cas 151564. Pieczonka, ewelina misztal, michal rachwalski, stanislaw lesniak. Synthesis of vicinal haloamines from vinyl aziridines. Synthetic applications of nh aziridine containing compounds. 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. Montmorillonite k10 as solid acid catalyzes a stereoselective reaction of imines with ethyl diazoacetate to yield cis aziridines. It is a colorless, toxic, volatile liquid that is of significant practical interest. 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. First graphene oxide promoted metalfree nitrene insertion.
Direct stereospecific synthesis of unprotected nh and n. Ring expansions of activated aziridines and azetidines. 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. Direct stereospecific synthesis of unprotected nh and nme aziridines from olefins jawahar l.
Wenker synthesis is a typical method for synthesis of aziridines in which 2amino alcohols from natural or synthetic amino acids are cyclized by base. 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. In recent years, our search for new nitrogen transfer reactions has concentrated on aziridine chemistry. Aziridines are important precursors for the synthesis of various nitrogencontaining bioactive molecules, such as heterocycles, alkaloids and amino acids. Advances in nitrogen transfer reactions involving aziridines. A deuteriumlabeling experiment indicates that the oxidative. Nsulfonyl aziridines undergo oxidative addition to palladium0 complexes generated in situ from mixtures of pd2dba3 and 1,10phenanthroline. The utility of epoxides, for example, in the enantioselective synthesis of oxygen.
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. Green synthesis of azetidines quinodoze and his colleagues demonstrated an easily practicable method to access. Aziridines article about aziridines by the free dictionary. First graphene oxide promoted metal free nitrene insertion into olefins in water. Rethinking their application and manipulation in synthesis christopher r. Several routes have been developed for the syntheses of aziridines aziridination.
Aziridines and epoxides in organic synthesis wiley. Paz with a defined tacticity can be synthesized from aziridines bearing a. Journal of the american chemical society 2009, 1 22, 75287529. Synthetic applications of nh aziridine containing compounds shannon marie decker master of science department of chemistry university of toronto. 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. Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. May 28, 2003 first graphene oxide promoted metal free nitrene insertion into olefins in water. Besides these three classical approaches to synthesize aziridines, the latter.
Remarkably, both electronrich and electronpoor olefins are converted to aziridines with high efficiency. Synthesis of nsulfonyl aziridines through regioselective opening of epoxides under solidliquid ptc conditions. In addition, oxazolidinones are important heterocyclic compounds showing application as intermediates and chiral auxiliaries in organic synthesis. Aziridine is the organic compounds consisting of the threemembered heterocycle ch 2 2 nh. Pdf aziridines are important precursors for the synthesis of various. The class of aziridines are of broader interest in medicinal chemistry. Several drugs feature aziridine rings, including mitomycin c, porfiromycin, and azinomycin b carzinophilin. Aziridines can be prepared in organic synthesis in several ways. Review recent synthetic applications of chiral aziridines 49 synthesis 2000, no. The synthesis and applications of nalkenyl aziridines. Tetrahedron tetrahedron 55 1999 63876394 pergamon synthesis of nsulfonyl aziridines through regioselective opening of epoxides under solidliqui. However,apractical,functionalgrouptolerant and environmentally benign direct preparation of nhaziridinesfromstructu rallydiverseolefinshas so far eluded synthetic chemists 2431. The resulting azapalladacyclobutane complexes undergo intramolecular carbopalladation in the presence of copperi iodide to afford azapalladabicyclo3. Several synthetic approaches toward 2carboxymethylaziridines based on the di.
Synthesis of nsulfonyl aziridines through regioselective. 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. Synthesis of chiral 12aminoalkylaziridines via a self. 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. Synthesis and reactivity of azapalladacyclobutanes. A novel process for the highly stereoselective synthesis of isa247 voclosporin and close analogues. A novel process for the highly stereoselective synthesis of. Facile and green synthesis of saturated cyclic amines. Aziridine is the organic compounds consisting of the threemembered heterocycle ch22nh. 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. 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. These aziridines undergo a ringopening reaction with a variety of carbon and heteronucleophiles, in good yield, and generally with good regioselectivity. The reactions proceeded readily at room temperature in short reaction times, providing the products in very good yields and. Efficient synthesis of diarylmethylamines via lewis acid catalyzed friedelcrafts reactions of donoracceptor aziridines with n,ndialkylanilines.
Multiple catalytic methods have been developed to make aziridinesstrained triangular carbonnitrogencarbon rings that function as versatile synthetic intermediates. Molecules free fulltext stereoselective multicomponent. May 02, 20 general procedures for the synthesis of ndiphenylphosphinyl vinyl aziridines. 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. Most alkenyl boronic acids can be introduced into the reaction as the free boronic acids. Catalytic asymmetric synthesis of trisubstituted aziridines. The in situ generation of dialkyldithiocarbamates provided a simple, user. General transformations of aziridines because aziridines are closely related in structure to oxiranes and cyclopropanes, the approaches to their synthesis are very similar.
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. This account highlights our efforts toward the synthesis and functionalization of aziridines. Most contemporary methods of chiral aziridine preparation have relied on the chiral pool. The synthesis and applications of nalkenyl aziridines tspace. Aziridines are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine nr and two methylene bridges cr 2.
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