Aziridines are versatile and powerful building blocks in organic synthesis due to their high reactivity as well as stereo. 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. Aziridines, the nitrogenous analogues of epoxides, have until recently excited far less interest amongst synthetic organic chemists than their oxygenated counterparts, with some justification. Rethinking their application and manipulation in synthesis christopher r. A general strategy for the synthesis of enantiomerically. Azetidines and aziridines through nickelcatalyzed cross. Synthesis and reactivity of azapalladacyclobutanes. 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. Pdf synthesis of chiral 12aminoalkylaziridines via a self. Amino acid synthesis by aziridine ring opening reaction is a good example to the use of aziridines. In addition, we have expanded this concept to the synthesis of enantiomerically pure, terminal alkyl aziridines. Besides these three classical approaches to synthesize aziridines, the latter. Catalytic asymmetric synthesis of trisubstituted aziridines. 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.
The resulting azapalladacyclobutane complexes undergo intramolecular carbopalladation in the presence of copperi iodide to afford azapalladabicyclo3. Benzenesulfonyl aziridines of these compounds were prepared and their acetolysis was studied. Aziridines are highly useful compounds as building blocks for the synthesis of important organic compounds. Synthesis and rearrangement control of substituted. Aziridines, the triangular, comparably highly strained nitrogen analogs of epoxides, are important synthetic intermediates i. The observed excellent yields, regioselectivities and enantioselectivities find no rivals in other organocatalytic aziridine synthesis. Nsulfonyl aziridines undergo oxidative addition to palladium0 complexes generated in situ from mixtures of pd2dba3 and 1,10phenanthroline. Most contemporary methods of chiral aziridine preparation have relied on the chiral pool. Pdf a novel approach to the synthesis of optically pure 12aminoalkyl aziridines via a nucleophilic ringopening reaction of. A general strategy for the synthesis of enantiomerically pure. The synthesis and applications of nalkenyl aziridines. 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. Synthesis of 2, 3 fatty aziridines rauf 1984 journal. The purpose of synthesizing such heterocycles was for there known biological activity.
This thesis describes the synthesis and ring opening reactions of aziridines performed under batch as well as continuous flow. A photoassisted nicatalyzed reductive crosscoupling between tosylprotected alkyl aziridines and commercially available heteroaryl iodides is reported. Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. Tetrahedron tetrahedron 55 1999 63876394 pergamon synthesis of nsulfonyl aziridines through regioselective opening of epoxides under solidliqui. Catalyzed reactions of allylamines with aryl and alkenyl halides. 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. 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. Addition reactions of thioamide dianions that were derived from n. 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.
The class of aziridines are of broader interest in medicinal chemistry. Thus, aziridines possess potential as building blocks in the preparation of combinatorial libraries for biological high. Because of the potential for increased efficiency and selectivity, along with the advantages of environmentally benign synthetic procedures. Ethyleneimine, stabilized appears as a clear colorless liquid with an ammonia like odor. 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 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 deuteriumlabeling experiment indicates that the oxidative.
Several synthetic approaches toward 2carboxymethylaziridines based on the di. Aziridines and epoxides in organic synthesis wiley. Synthesis and nucleophilic opening of a new symmetric bis. 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 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. Wenker synthesis of aziridines and the development of a biphasic system this item was submitted to loughborough universitys institutional repository by thean author. Enantioselective synthesis of aziridines using asymmetric transfer hydrogenation as a precursor for chiral derivatives used. Several drugs feature aziridine rings, including mitomycin c, porfiromycin, and azinomycin b carzinophilin. Synthesis of nsulfonyl aziridines through regioselective. 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. 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. There are numerous methods for the synthesis of aziridines and azirines. Regiodivergent ring opening of chiral aziridines science.
Mesofluidic technology allowed for a rapid screening of different parameters and a quick identification 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. Direct and stereospecific synthesis of nh and nalkyl aziridines. Aziridines are important precursors for the synthesis of various nitrogencontaining bioactive molecules, such as heterocycles, alkaloids and amino acids. The reactions of imines gave the addition products of n. Aziridines are ubiquitous in bioactive molecules and often serve as key synthetic building blocks. Synthesis and reactions of aziridines via batch and flow processes. 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 are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine nr and two methylene bridges cr 2. 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. Stereoselective multicomponent reactions in the synthesis. A mechanism to explain this novel reaction is proposed. Direct stereospecific synthesis of unprotected nh and n. The efficient synthesis of small molecules that collectively comprise optimal smallmolecule screening collections is an important goal.
Pdf synthesis of oxazolinyl aziridines vito capriati. Wulffs group has developed a robust catalytic asymmetric aziridination. 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. This mild and modular method proceeds in the absence of stoichiometric heterogeneous reductants and uses an inexpensive organic photocatalyst to access medicinally valuable. Kinetic resolution of strained threemembered rings has proven broadly useful for the generation of enantiopure organic intermediates. Pdf aziridines are important precursors for the synthesis of various nitrogen containing bioactive molecules, such. Aziridines, besides the synthesis of pyrroles, have been employed in the synthesis of imidazolines, thiazolines, oxazolines, and 2,3dihydrobenzofurans. Aziridine is the organic compounds consisting of the threemembered heterocycle ch22nh. A straightforward synthesis of aziridines is reported from electronrich azides, electrondeficient olefins, and triflic acid in cold acetonitrile. Remarkably, both electronrich and electronpoor olefins are converted to aziridines with high efficiency.
Pdf enantioselective synthesis of aziridines using. Aziridine is the organic compounds consisting of the threemembered heterocycle ch 2 2 nh. Filling a gap in the literature, this clearly structured book. A reaction of a chiral aldimine derived from phenylalaninal proceeded with high diastereoselectivity. 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.
Chiral aziridines are prevalently found in natural products and artificially made bioactive molecules, thus receiving significant attention in the past decades. Observations on the modi ed wenker synthesis of aziridines. 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. Direct stereospecific synthesis of unprotected nhnme. The article attempts to present, as best as possible, a list of references covering amphetamine synthesis from 1900 2009. Aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. 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. It is a colorless, toxic, volatile liquid that is of significant practical interest. Synthesis and reactivity of 2 carboxymethylaziridine. Current methods for the rhiicatalyzed nh aziridination of unactivated olefins. A general synthesis of various substituted benzonorbornene derivatives is described. 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.
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. The need to remove activating groups from the aziridine nitrogen atom e. Asymmetric synthesis of cf2functionalized aziridines by. With the development of the catalytic asymmetric synthesis of trisubstituted aziridines presented here, it will be of interest to investigate the mechanistic di. 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.
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. The parent compound is aziridine or ethylene imine, with molecular formula c 2 h 4 nh. 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 synthesis and applications of nalkenyl aziridines nicholas a.
Observations on the modi ed wenker synthesis of aziridines and the development of a biphasic system. Synthesis of chiral 12aminoalkylaziridines via a selfopening. Aziridine is a saturated organic heteromonocyclic parent, a member of aziridines and an azacycloalkane. Although this reaction is studied by many groups, the synthesis of amino phosphonic acids is less explored. Pdf an improved and mild wenker synthesis of aziridines.
Synthesis of 2 carboxymethylaziridine derivatives in the following section, synthesis of 2 carboxymethyl aziridine derivatives will be dealt with. Ring expansions of activated aziridines and azetidines in synthesis of 4to 7membered heterocycles by ring expansion. Preparation of the fatty acid aziridines 106115 has been described. The incorporation of nitrogen into a molecule during chemical synthesis is not always straightforward, but aziridines offer a potentially attractive.