S1 supporting information asymmetric synthesis of trisubstituted aziridines via azadarzens reaction of chiral sulfinimines toni moragas, ian churcher. 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. Aziridines are highly versatile intermediates in organic synthesis due to their easy access and their susceptibility to ringopening by facile cn bond cleavage. The simplest and oldest preparation of aziridines is the ring closure of a. This salt is then reacted with sodium hydroxide in the second step forming aziridine. Synthesis of imidazolines from aziridines by michael robert kuszpit the majority of the work in this thesis presents a new method to syntheisize imidazolines from both chiral and racemic aziridines. A novel approach to the synthesis of optically pure 12aminoalkyl aziridines via a nucleophilic ringopening reaction of aziridine is presented.
A highly enantioselective synthetic route to hexahydropyrrolo2,3bindoles via lewis acidcatalyzed sn2type ring opening of activated aziridines with indoles having substitutions at 3 and other positions followed by cyclization in a domino fashion has been developed. Synthesis of chiral n phosphoryl aziridines through enantioselective aziridination of alkenes with phosphoryl azide via coiibased metalloradical catalysis. Wenker synthesis is a typical method for synthesis of aziridines in which 2amino alcohols from natural or synthetic amino acids are cyclized by base. Asymmetric synthesis of cf2functionalized aziridines by. 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. Pdf aziridines are important precursors for the synthesis of various nitrogencontaining bioactive molecules, such as heterocycles, alkaloids. Organolithiuminduced alkylative ring opening of aziridines. Styrenes reacted with sulfonamide in the presence of potassium carbonate and iodine in chcl 3 under visible light irradiation to produce the corresponding aziridines in good yields. Jan 09, 2006 the renowned editor has succeeded in gathering together excellent authors to cover synthesis, applications, and the biological aspects in equal depth.
Most contemporary methods of chiral aziridine preparation have relied on the chiral pool. Domino ringopening cyclization of activated aziridines with. Aziridines are valuable strained small heterocycles of interest in preparative organic synthesis. Stockman school of chemistry, university of nottingham, nottingham, ng7 2rd, u. These aziridines undergo a ringopening reaction with a variety of carbon and heteronucleophiles, in good yield, and generally with good regioselectivity. May 02, 20 predominantly endiphenylphosphinyl vinyl aziridines are prepared by a reaction of ndiphenylphosphinyl imines with. Pdf aziridines are important precursors for the synthesis of various nitrogen containing bioactive molecules, such as heterocycles, alkaloids. 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. 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. Krinitskaya 1 russian chemical bulletin volume 56, pages 527 531 2007 cite this article. Isothiazoles in the design and synthesis of biologically active. Yudin, aziridines and epoxides in organic synthesis, wileyvch, weinheim 2006. Preparation and alkylative ring opening of transaziridine 49a. Synthesis and nucleophilic opening of a new c 2 symmetric bisaziridine.
Small ring heterocycles, such as epoxides and aziridines, are present. Tetsuji kametani and toshio honda, application of aziridines to the synthesis of natural products, 10. Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. The original wenker synthesis of aziridine itself takes place in two steps. This thesis describes the synthesis and ring opening reactions of aziridines performed under batch as well as continuous flow conditions. 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. Glaxosmithkline, gunnels wood road, stevenage, sg1 2ny, u. Aziridines article about aziridines by the free dictionary. Aziridines also have an important role in the preparation of further types of nitrogencontaining compounds 810. 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. Friedelcrafts reactions of donoracceptor aziridines with. The purpose of synthesizing such heterocycles was for there known biological activity. An updated library on the synthesis of aziridines bentham science. N2haloalkyl and n3haloalkyl imines are convenient substrates for the synthesis of aziridines and azetidines via a twostep process involving nucleophile induced addition at the imino bond followed by intramolecular nucleophilic substitution.
Synthesis and reactions of aziridines via batch and flow. 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. In the first step ethanolamine is reacted with sulfuric acid at high temperatures 250 c to form the sulfate monoester. Synthesis and properties of bicyclic aziridines, derivatives of triacetoneamine l.
Aziridines and epoxides are among the most widely used intermediates in organic synthesis, acting as precursors to complex molecules due to. 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. Beilstein journal of organic chemistry 2014, 10, 12821289. If the inline pdf is not rendering correctly, you can download the pdf file here. Files available from the acs website may be downloaded for personal use only.
Synthesis of aziridines from alkenes and aryl azides with a reusable macrocyclic tetracarbene iron catalyst. Chiral aziridines are prevalently found in natural products and artificially made bioactive molecules, thus receiving significant attention in the past decades. Straightforward synthesis of 1alkyl2trifluoromethyl. 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. Several synthetic approaches toward 2carboxymethylaziridines based on the di. Synthesis and nucleophilic opening of a new symmetric bis. Aziridines are important precursors for the synthesis of various nitrogencontaining bioactive molecules, such as heterocycles, alkaloids and amino acids. Synthesis of aziridines from alkenes and aryl azides with. Several routes have been developed for the syntheses of aziridines aziridination. Divided roughly equally between aziridines and epoxides, the twelve chapters discuss. The observed excellent yields, regioselectivities and enantioselectivities find no rivals in other organocatalytic aziridine synthesis. Stereoselective multicomponent reactions in the synthesis or.
Fluoroamines by lewis base catalyzed hydrofluorination of aziridines julia a. Synthesis of aziridines from alkenes and aryl azides with a. Department of chemistry, the university of tennessee, knoxville, tennessee 379961600, united states. Catalytic asymmetric transformations of racemic aziridines. Asymmetric synthesis of trisubstituted aziridines via aza. Ring opening of nunfunctionalised nh aziridines allows direct access to aminoacid derivatives, yet. Synthesis of 2 carboxymethylaziridine derivatives in the following section, synthesis of 2 carboxymethyl aziridine derivatives will be dealt with.
Application of aziridines for the synthesis of isoquinoline. 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. Aziridines and epoxides in organic synthesis wiley online books. Epoxides can be converted into aziridines by nucleophilic attack of azide ion, the staudinger reaction, and aziridine ring. Synthesis and properties of bicyclic aziridines, derivatives. Crossref sarah shtelzer, tuvia sheradsky, jochanan blum and shmuel zitrin, the chemistry of arene imines. 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. Wulffs group has developed a robust catalytic asymmetric aziridination reaction providing. First synthesis of aziridines using polymersupported triphenylphosphine isabelle mccort, ste. Synthesis of aziridines nucleophilic ringopening of aziridines and epoxides. Chapter 1 gives a brief introduction to the synthesis and ring opening reactions of aziridines. The formation of 12aminoalkyl aziridines, starting from optically pure nh.
Epoxides can be converted into aziridines by nucleophilic attack of azide ion, the staudinger reaction, and aziridine ring formation with elimination of triphenylphosphine oxide. Some recent advances in the field of stereoselective synthesis of aziridines focusing on new methodologies, mechanistic insights, and the scope and limitations of each strategy are studied. 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. Rethinking their application and manipulation in synthesis christopher r. The primary synthetic approaches involve either the direct aziridination of an olefin or the reaction of an imine with diazoalkanes.
An amine functional group displaces the adjacent halide in an intramolecular nucleophilic substitution reaction to generate an aziridine. A twostep synthesis under continuousflow conditions. 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. 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. Synthesis and reactions of aziridines via batch and flow processes. Synthetic applications of nh aziridine containing compounds. Synthesis of chiral 12aminoalkylaziridines via a self. Studies have been made on the possible synthesis of 1 arylethynylaziridines by oxidative condensation of phenylacetylene with aziridine and by alkylation of aziridine with 1. Synthesis and reactivity of 2 carboxymethylaziridine. Catalytic asymmetric synthesis of trisubstituted aziridines. The synthesis and applications of nalkenyl aziridines. The reaction takes place under mild conditions in the presence of znbr2 with moderate chemical yields.
As a consequence, the preparation of aziridines is of great importance 11. A mild, convenient protocol for the synthesis of cisaziridines employs a catalytic amount of bronsted acid. Doyle department of chemistry, princeton university frick chemical laboratory, princeton, nj 08544 usa email. The parent compound of the aziridines is called aziridine or ethylene imine with molecular formula c 2 h 5 n cas 151564. An efficient and straightforward approach towards the synthesis of 1alkyl2 trifluoromethyl aziridines starting from 1,1,1trifluoroacetone via imination. Threecomponent synthesis of highly functionalized aziridines. With the development of the catalytic asymmetric synthesis of trisubstituted aziridines presented here, it will be of interest to investigate the mechanistic di.
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