In dialkyl ethers, oxygen is sp3 hybridized with bond angles of approximately 109. The second edition of comprehensive organic synthesiswinner of the 2015. This account details new reactions and synthetic uses of lithiated epoxides and aziridines that have been developed in the principal authors laboratories. Aziridines are the smallest possible azaheterocycles and well known to organic chemists for their tremendous potential in the design of organic synthesis and medicinal chemistry 47. It has been estimated that among all natural products, the average number of nitrogen atoms per molecule is 0. An alternative strategy for opening epoxides was implemented that employed a potassium carb. Organocatalyzed enantioselective desymmetrization of aziridines and epoxides pingan wang.
The literature of heterocyclic chemistry, part x, 20052007. A reaction of a chiral aldimine derived from phenylalaninal proceeded with high diastereoselectivity. Ringopening of cycloalkane epoxides and aziridines with. Organocatalysis in synthesis and reactions of epoxides and aziridines. 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. View notes aziridines from chem 701 at university of pennsylvania. Ring opening of nunfunctionalised nh aziridines allows direct access to aminoacid derivatives, yet the published methodology is currently limited for this transformation 1620. Alcohols, ethers, epoxides, sulfides organic chemistry. Several drugs feature aziridine rings, including mitomycin c, porfiromycin, and azinomycin b carzinophilin. Aziridines and their derivatives are potent pharmacological agents.
Divided roughly equally between aziridines and epoxides, the twelve chapters discuss. The diastereoselective synthesis of 1,3diamines and amino. Asymmetric synthesis of epoxides and aziridines from aldehydes and imines varinder k. Carbonylation as a method for synthesizing organic.
Direct stereospecific synthesis of unprotected nhnme. The parent compound is aziridine or ethylene imine, with molecular formula c2h5n. A cyclic ether in which oxygen is one atom of a threemembered ring. Because the reaction ls slow, at least a 15minute reaction time is generally allowed before back titrating the excess acid. Synthesis of nsulfonyl aziridines through regioselective. Sos water in organic synthesis sos stereoselective synthesis. Download ris reference manager download bib bibtex cited references. Aziridine is the organic compounds consisting of the threemembered heterocycle ch 2 2 nh. Asymmetric synthesis of epoxides and aziridines from aldehydes and imines. Threecomponent synthesis of highly functionalized aziridines containing a peptide side chain and their onestep transformation into. Aziridines, the triangular, comparably highly strained nitrogen analogs of epoxides, are important synthetic intermediates i.
Azacycloalkanes from epoxides and aziridines springerlink. Aziridines and epoxides in organic synthesis request pdf. The renowned editor has succeeded in gathering together excellent authors to cover synthesis, applications, and the biological aspects in equal depth. Everyday low prices and free delivery on eligible orders. Carbonylation as a method for synthesizing organic intermediates and substrates from epoxides and aziridines venkata a. Synthesis of aziridines, nucleophilic ringopening of aziridines and epoxides, organic synthesis with. Twostep synthesis of nsulfonyl aziridines from epoxides.
Filling a gap in the literature, this clearly structured book presents the much. A chairlike sixmembered transition state with minimized 1,3diaxial interactions explains the relative stereoselectivity of the cyclization reaction. Crossref sarah shtelzer, tuvia sheradsky, jochanan blum and shmuel zitrin, the chemistry of arene imines. Epoxides 1 and aziridines 2 are the most useful synthetic intermediates in organic synthesis. With the potential to introduce two adjacent chiral centers with high atom economy, this methodology rightly deserves a place of prominence in synthetic organic chemistry. Aziridines and epoxides in organic synthesis wiley online books download pdf. Among these, the azidolysis of epoxides and aziridines are the most important for preparation of azidoalcohols 5 and azidoamines 6. Aziridines aziridines are the aza analogues of epoxides and are prepared by similar reactions. Carbonylation as a method for synthesizing organic intermediates and substrates from epoxides and aziridines. How acidcatalyzed reactions can open the highly strained ring of an epoxide. Aug 25, 2006 the renowned editor has succeeded in gathering together excellent authors to cover synthesis, applications, and the biological aspects in equal depth. In literature examples where ringopening protocols have been developed, synthesis of the starting nhaziridine2carboxylates is multistep and lowyielding.
Ring opening reactions of heterocycles with selenium and tellurium. Reactions of epoxides ethers are not normally susceptible to attack by nucleophiles. The class of aziridines are of broader interest in medicinal chemistry. 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.
Direct stereospecific synthesis of unprotected nh and n. Because of their ring strain and high reactivity, their reactions with various nucleophiles lead to high regio and stereoselective ringopening products 3,4. Direct titration of epoxy compounds and aziridines sir. In particular, the catalytic coupling of co2 with energyrich substrates, such as epoxides and aziridines, to generate polycarbonates.
When you see an ether in a synthesis problem, remember the williamson ether synthesis. 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. 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. It is a colorless, toxic, volatile liquid that is of significant practical interest. Aziridines, the nitrogenous analogues of epoxides, have until recently excited far less interest amongst synthetic organic chemists than their oxygenated counterparts, with some justification. The synthesis and applications of nalkenyl aziridines. Abstract ringopening reactions of epoxides and aziridines have been extensively studied. Aziridines and epoxides in organic synthesis by andrei k.
The diastereoselective synthesis of 1,3diamines and amino alcohols via 2azaallyl anion ringopening of aziridines and epoxides. Synthesis of complex molecules by rearrangement reactions of epoxides. Aziridines aziridines aziridines are the aza analogues of. Aziridines are highly reactive compoundsstill several natural products are found to bear such skeleton. A simpler route for making nitrogenalkene rings science. Nitrogen is a key component of many natural products and drug molecules.
Ethers, sulfides omit, and epoxides chapter 11 2 structure the functional group of an ether is an oxygen atom bonded to two carbon atoms. Aziridines and epoxides in organic synthesis wileyvch. His research interests include environmentally benign organic syntheses, mainly organocatalytic reactions. Regiodivergent ring opening of chiral aziridines science. Csir net johnson corey chaykovsky reaction organic. Because of the strain associated with the threemembered ring, epoxides readily undergo a variety of ringopening reactions. 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.
The influence of different protecting groups on the hydroxyl group in the ringopening reactions of cis and trans 3hydroxy1,2cycloalkane epoxides with aromatic amines was studied. Nickelcatalyzed borylative ring opening of vinyl epoxides. Alcohol and thiol groups are important functional groups for applications ranging from enzyme reactions to making flexible contact lenses. Epoxides and aziridines in click chemistry aziridines and. Aziridines and epoxides in organic synthesis yudin, andrei k. Aziridines are widely used as intermediates in organic synthesis, acting as precursors to complex molecules due to the strains incorporated in their skeletons. Comprehensive organic synthesis 2nd edition elsevier. The method which involves epoxide ring opening with sulfonamides and subsequent mesylationcyclisation, is particularly suitable for variation of the nsulfonyl substituent.
An alternative strategy for opening epoxides was implemented that employed a potassium carboxylate in the presence of its conjugate acid in a solvent mixture. Oxidation of terminal ntertbutylsulfinyl aziridines provides synthetically useful terminal nbus bus tertbutylsulfonyl aziridines. 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. Tetsuji kametani and toshio honda, application of aziridines to the synthesis of natural products, 10. Their synthetic utility lies in the fact that they can be ringopened with a broad range of nucleo. Organocatalyzed enantioselective desymmetrization of. This lesson examines the use of peroxyacids to form epoxide rings and the acidic opening and cleavage of those epoxide rings. Epoxide formation and acidic epoxide opening youtube. Aziridines and epoxides in organic synthesis general monograph. Fivemembered oxaza heterocyclic compounds on the basis of. 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. A versatile method for the synthesis of nitrogencontaining molecules is to use nitrogenbridged alkenes aziridines as building blocks, as the ring. Highly regio and stereoselective ringopening of epoxides. The johnsoncoreychaykovsky reaction is a chemical reaction used in organic chemistry for the synthesis of epoxides, aziridines, and cyclopropanes.
Moreover, the aziridine presenting a complex steroid structure was found to be a suitable partner, leading to 3y in 84% yield. A mild, convenient protocol for the synthesis of cisaziridines employs a catalytic amount of bronsted acid. In organic chemistry, we will learn about the reactions chemists use to synthesize crazy carbon based structures, as well as the analytical. Rethinking their application and manipulation in synthesis christopher r. Aziridines are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine nr and two methylene bridges cr 2.
Scheme 6 ring opening reactions of epoxides and aziridines with. This new process combines nitrogen and hydrogen atoms in triangular aziridine products that are readily available to react with. Jan 31, 2014 describes the use of epoxides in synthesis to place two functional groups on adjacent carbons and to control the stereochemistry of the products formed from epoxides. Cucatalyzed crosscoupling reactions of vinyl epoxide with. 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 properties. Aziridine is a saturated organic heteromonocyclic parent, a member of aziridines and an azacycloalkane. The possibility of epoxides conversion into aziridines was considered. A highly diastereoselective desymmetrization of pquinamines via regioselective ring opening of epoxides and aziridines under mild conditions has been developed. Epoxides and aziridines in click chemistry aziridines. The uncatalyzed allylation of aldehydes allows obtaining challenging bishomoallylic alicyclic 1,3diols and 1,3amino alcohols with remarkably high stereoselectivities. Then we will be ready to learn about some reactions that involve alcohols, ethers, epoxides, thiols, and sulfides as both reactants and products. Their application in organic synthesis and asymmetric catalysis is also reported, along with. This organic chemistry video tutorial provides a basic introduction into the reactions of ethers and epoxides.
Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. A mechanism to explain this novel reaction is proposed. Using carbon dioxide as a building block in organic synthesis nature. Methods of preparation of azetidines, pyrrolidines, and piperidines from epoxides and aziridines were analyzed. Configured cyclophellitol epoxides and aziridines sybrin p. Vinyl epoxides are easily prepared using simple synthetic routes and are important. Diastereoselective desymmetrization of pquinamines. In this paper, we would like to describe an efficient method for the ringopening reaction of epoxides 1 or nsubstituted aziridines 2 in water catalyzed by polymersupported quarternary ammonium bisulfate d201hso 4, which was facilely prepared and recyclable, to obtain 1,2diols 3 or. Buy aziridines and epoxides in organic synthesis by yudin, andrei k. Aug 06, 2011 to add the methyl group, convert the alcohol to a ketone which is an electrophile, and then add methyl grignard a nucleophile. Onepot acidcatalyzed ringopeningcyclizationoxidation of. Catalytic asymmetric epoxide ringopening chemsitry.
The utility of epoxides, for example, in the enantioselective synthesis of oxygen. In aziridines and epoxides in organic synthesis yudin ak. Jan 03, 2014 aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. The weak basicity of aziridine and its derivatives is ascribed to the strain in the 3membered ring compound. The study, conducted at rice university, us, demonstrated the possibility of inexpensive organic synthesis to catalyse the transfer of nitrogen atoms to olefins, unsaturated organic compounds also known as alkenes. Ringopening of hindered cyclic epoxides with potassium. Coppericatalyzed asymmetric decarboxylative mannich reaction. Epoxidation and aziridination reactions using chalcogenides. Recent applications of aziridine ring expansion reactions. A mild ring opening of vinyl epoxides and aziridines with b2pin2 catalyzed by ni0binap affords new functionalized allylic boron derivatives which undergo sequential transformations. Download ris reference manager download bib bibtex back to article. Less hindered aziridines can be obtained in high yields by tosylation and in situ cyclization effected by potassium hydroxide in waterdichloromethane. Dec 18, 2009 kinetic resolution of strained threemembered rings has proven broadly useful for the generation of enantiopure organic intermediates. Pergamon tetrahedron 55 1999 63876394 tetrahedron synthesis of nsulfonyl aziridines through regioselective opening of epoxides under solidliquid ptc conditions domenico albanese, dario landini, michele penso, silvia petricci centro cnr and dipartimento di chimica organica e industriale delluniveit.
Direct stereospecific synthesis of unprotected nh and nme. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Aziridines and epoxides in organic synthesis sigmaaldrich. Technique to synthesise aziridines developed by researchers. The link of nucleophilic ring opening is given below s.
Ethylene oxide is a valuable building block for organic synthesis because each of its carbons may be converted to a functional group. Aziridines and epoxides in organic synthesis wiley. The determination of the oxirane ring in organic compounds has generally involved reaction with excess hydro chloric acid in a vayiety of solvents. Aziridines are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine group nh and two methylene bridges ch2. Syntheses of substituted furans and pyrroles by platinumcatalyzed cyclizations of propargylic oxiranes and aziridines in aqueous media masahiro yoshida, mohammad alamin, kozo. Epoxides in complex molecule synthesis aziridines and. The parent compound is aziridine or ethylene imine, with molecular formula c 2 h 4 nh. A convenient and highyielding twostep synthesis of nsulfonyl aziridines starting from epoxides is described. Hydrolysis of epoxides and aziridines catalyzed by polymer. Two alternative and complementary onepot procedures for the direct transformation of 2amino alcohols to ntosyl aziridines are presented. Azaheterocyclic compounds are wellknown to have diverse types of biological activity. Efficient syntheses of optically active neolignans ligraminol d and e were achieved in four simple steps starting from easily available chiral benzyl glycidyl ethers. 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.
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