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. Several drugs feature aziridine rings, including mitomycin c, porfiromycin, and azinomycin b carzinophilin. Ethyleneimine, stabilized appears as a clear colorless liquid with an ammonia like odor. Azetidines and aziridines through nickelcatalyzed cross.
Besides these three classical approaches to synthesize aziridines, the latter. Synthesis and reactions of aziridines via batch and flow processes. The synthesis and applications of nalkenyl aziridines. A general strategy for the synthesis of enantiomerically. A straightforward synthesis of aziridines is reported from electronrich azides, electrondeficient olefins, and triflic acid in cold acetonitrile. This thesis describes the synthesis and ring opening reactions of aziridines performed under batch as well as continuous flow. Chiral aziridines are prevalently found in natural products and artificially made bioactive molecules, thus receiving significant attention in the past decades. Asymmetric synthesis of cf2functionalized aziridines by. Aziridines, the triangular, comparably highly strained nitrogen analogs of epoxides, are important synthetic intermediates i. Direct and stereospecific synthesis of nh and nalkyl aziridines.
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. A general synthesis of various substituted benzonorbornene derivatives is described. 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. Pdf a novel approach to the synthesis of optically pure 12aminoalkyl aziridines via a nucleophilic ringopening reaction of. The resulting azapalladacyclobutane complexes undergo intramolecular carbopalladation in the presence of copperi iodide to afford azapalladabicyclo3. Pdf enantioselective synthesis of aziridines using. 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. Herein we demonstrate a complementary approach whereby a single catalyst transforms a racemic mixture of aziridines to a pair of regioisomeric products, each in good yield with exceptionally high enantioselectivity. Synthesis of 2, 3 fatty aziridines rauf 1984 journal. Aziridines are important precursors for the synthesis of various nitrogencontaining bioactive molecules, such as heterocycles, alkaloids and amino acids. Aziridines are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine nr and two methylene bridges cr 2. Synthesis of 2 carboxymethylaziridine derivatives in the following section, synthesis of 2 carboxymethyl aziridine derivatives will be dealt with. A mechanism to explain this novel reaction is proposed.
Addition reactions of thioamide dianions that were derived from n. A general strategy for the synthesis of enantiomerically pure. In addition, we have expanded this concept to the synthesis of enantiomerically pure, terminal alkyl aziridines. Aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. Pdf synthesis of chiral 12aminoalkylaziridines via a self. The class of aziridines are of broader interest in medicinal chemistry.
The reactions of imines gave the addition products of n. Amino acid synthesis by aziridine ring opening reaction is a good example to the use of aziridines. Observations on the modi ed wenker synthesis of aziridines. Although this reaction is studied by many groups, the synthesis of amino phosphonic acids is less explored. Wenker synthesis is a typical method for synthesis of aziridines in which 2amino alcohols from natural or synthetic amino acids are cyclized by base. In this field, chiral aziridines form an attractive class of compounds, since they are available in enantiomerically pure or highly enriched form by a variety of procedures and can be used for asymmetric synthesis in a number of different ways. 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. Benzenesulfonyl aziridines of these compounds were prepared and their acetolysis was studied. The observed excellent yields, regioselectivities and enantioselectivities find no rivals in other organocatalytic aziridine synthesis.
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. Stereoselective multicomponent reactions in the synthesis. Pdf an improved and mild wenker synthesis of aziridines. 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. 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. It is a colorless, toxic, volatile liquid that is of significant practical interest. Pdf synthesis of oxazolinyl aziridines vito capriati.
Enantioselective synthesis of aziridines using asymmetric transfer hydrogenation as a precursor for chiral derivatives used. The article attempts to present, as best as possible, a list of references covering amphetamine synthesis from 1900 2009. The need to remove activating groups from the aziridine nitrogen atom e. Nsulfonyl aziridines undergo oxidative addition to palladium0 complexes generated in situ from mixtures of pd2dba3 and 1,10phenanthroline. A reaction of a chiral aldimine derived from phenylalaninal proceeded with high diastereoselectivity. Rethinking their application and manipulation in synthesis christopher r. Synthesis of nsulfonyl aziridines through regioselective.
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. Aziridines and epoxides in organic synthesis wiley. Ring expansions of activated aziridines and azetidines in synthesis of 4to 7membered heterocycles by ring expansion. Synthesis and reactivity of azapalladacyclobutanes. Synthesis and reactivity of 2 carboxymethylaziridine. Tetrahedron tetrahedron 55 1999 63876394 pergamon synthesis of nsulfonyl aziridines through regioselective opening of epoxides under solidliqui.
Al 2 o 3 nanoparticles, opening of the epoxide by nan 3, and cyclization of the azidoalcohol by ph 3 p followed by condensation of the resulting aziridines with formalin and secondary amines. 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. With this in mind, we have used nalkyl aziridines in a regio and stereochemically controlled synthesis of polycyclic heterocycles based on nucleophilic ring opening and subsequent intramolecular cyclization. Catalyzed reactions of allylamines with aryl and alkenyl halides. Direct stereospecific synthesis of unprotected nhnme. Wulffs group has developed a robust catalytic asymmetric aziridination. Several synthetic approaches toward 2carboxymethylaziridines based on the di. Thus, aziridines possess potential as building blocks in the preparation of combinatorial libraries for biological high. A deuteriumlabeling experiment indicates that the oxidative. Filling a gap in the literature, this clearly structured book. Observations on the modi ed wenker synthesis of aziridines and the development of a biphasic system. This mild and modular method proceeds in the absence of stoichiometric heterogeneous reductants and uses an inexpensive organic photocatalyst to access medicinally valuable. The sandmeyer reaction of anilines to generate aryl azides, followed by the ruporphyrincocatalyzed addition to styrenes affording naryl aziridines was successfully performed for the first time in mesoreactors, under continuousflow conditions.
The efficient synthesis of small molecules that collectively comprise optimal smallmolecule screening collections is an important goal. Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. Synthesis and nucleophilic opening of a new symmetric bis. A new synthetic application of vinyl aziridines as n. The synthesis and applications of nalkenyl aziridines nicholas a. Aziridine is the organic compounds consisting of the threemembered heterocycle ch 2 2 nh. 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. We report herein an intramolecular kitbhp mediated oxidative dehydrogenative csp3h amination reaction to synthesize a diverse array of trans2,3disubstituted aziridines in good yields under mild conditions. The incorporation of nitrogen into a molecule during chemical synthesis is not always straightforward, but aziridines offer a potentially attractive. 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.
Aziridines, besides the synthesis of pyrroles, have been employed in the synthesis of imidazolines, thiazolines, oxazolines, and 2,3dihydrobenzofurans. Because of the potential for increased efficiency and selectivity, along with the advantages of environmentally benign synthetic procedures. Catalytic asymmetric synthesis of trisubstituted aziridines. Current methods for the rhiicatalyzed nh aziridination of unactivated olefins.
Kinetic resolution of strained threemembered rings has proven broadly useful for the generation of enantiopure organic intermediates. Aziridines are highly useful compounds as building blocks for the synthesis of important organic compounds. Regiodivergent ring opening of chiral aziridines science. Aziridines are ubiquitous in bioactive molecules and often serve as key synthetic building blocks. With the development of the catalytic asymmetric synthesis of trisubstituted aziridines presented here, it will be of interest to investigate the mechanistic di.
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. Aziridines, the nitrogenous analogues of epoxides, have until recently excited far less interest amongst synthetic organic chemists than their oxygenated counterparts, with some justification. Direct stereospecific synthesis of unprotected nh and n. 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. Pdf aziridines are important precursors for the synthesis of various nitrogen containing bioactive molecules, such.
Aziridines are versatile and powerful building blocks in organic synthesis due to their high reactivity as well as stereo. Synthesis and rearrangement control of substituted. A photoassisted nicatalyzed reductive crosscoupling between tosylprotected alkyl aziridines and commercially available heteroaryl iodides is reported. Remarkably, both electronrich and electronpoor olefins are converted to aziridines with high efficiency. The purpose of synthesizing such heterocycles was for there known biological activity.
790 561 1378 274 803 274 981 1552 1147 91 1230 1544 1229 679 1077 298 646 1501 114 1431 1268 678 746 348 916 955 382 1099 800 1394 611