View table of contents for aziridines and epoxides in organic synthesis. Aziridines and epoxides are among the most widely used intermediates in organic synthesis, acting as precursors to. Aziridines and epoxides in organic synthesis 2006 yudin. Accordingly, selected examples from different methods reported in recent literature are described here. Oct 05, 2016 to the best of our knowledge, no such process has been demonstrated with halide nucleophiles.
Aziridines also have an important role in the preparation of further types of nitrogencontaining compounds 810. Diastereoselective desymmetrization of pquinamines. Advanced free radical reactions for organic synthesis 2004 togo. A short, highyielding protocol involving the enantioselective. Artificial neural network prediction of retention of amino acids in reversedphase hplc under application of linear organic modifier gradients and or ph gradients next article in special issue synthetic chiral derivatives of xanthones. Synthesis of nsulfonyl aziridines through regioselective.
The enantioselective catalytic desymmetrization of meso aziridines and meso epoxides by metalbased lewis acids cooperating with chiral ligands has been well established 1628. Thus, ringopenings of aziridines and epoxides have been applied industrially to produce a variety of bulk chemicals, including polyethylenimine, ethylene glycol, and epoxy resins. A highly diastereoselective desymmetrization of pquinamines via regioselective ring opening of epoxides and aziridines under mild conditions has been developed. Threecomponent synthesis of highly functionalized aziridines.
Divided roughly equally between aziridines and epoxides, the twelve chapters discuss. A simple and inexpensive ammonium persulfate salt enables the reaction of aziridines with. Organocatalyzed enantioselective desymmetrization of. In literature examples where ringopening protocols have been developed, synthesis. Transformations of vinylepoxides intermolecular opening with oxygen and nitrogen nucleophiles 1,2. The practical stereocontrolled synthesis of vicinal halohydrins and haloamines from vinyl epoxides and vinyl aziridines lukasz j. Nickelcatalyzed regiodivergent opening of epoxides with. 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. 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. The publication of this book, aziridines and epoxides in organic synthesis, is therefore timely, since there have. Furthermore, aziridines and epoxides serve as versatile intermediates in natural product and pharmaceutical synthesis.
Epoxides and aziridines in click chemistry aziridines and. Epoxides are produced biologically as oxidation products of alkenes and aromatic compounds. As a consequence, the preparation of aziridines is of great importance 11. A general, enantioselective synthesis of nalkyl terminal. The method which involves epoxide ring opening with sulfonamides and subsequent mesylationcyclisation, is particularly suitable for variation of the nsulfonyl substituent. Epoxides that are formed in the liver by cytochrome p450 undergo ringopening reactions.
A simple and inexpensive ammonium persulfate salt enables the reaction of aziridines with halogenated alcohols to proceed via an sn2type ring opening followed by cyclization of the resulting haloalkoxy amine. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. 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. Dec 31, 2010 the main features of this versatile synthesis of functionalized. Aziridine is the organic compounds consisting of the threemembered heterocycle ch 2 2 nh. Less hindered aziridines can be obtained in high yields by tosylation and in situ cyclization effected by potassium hydroxide in waterdichloromethane. 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. Aziridines and epoxides in organic synthesis ebook, 2006. The journal of organic chemistry 2014 79 22, 1094510955. Synthesis of aziridines nucleophilic ringopening of aziridines and. Carbonylation as a method for synthesizing organic. Aziridines are highly reactive compoundsstill several natural products are found to bear such skeleton. They can be applied to synthesize epoxides and aziridines, which are valuable small heterocycles. Carbonylation as a method for synthesizing organic intermediates and substrates from epoxides and aziridines venkata a.
Aziridines, the nitrogenous analogues of epoxides, have until recently excited far less interest amongst synthetic organic chemists than their oxygenated counterparts, with some justification. An amine functional group displaces the adjacent halide in an intramolecular nucleophilic substitution reaction to generate an aziridine. Nonactivated aziridines as building blocks for the synthesis. It is a colorless, toxic, volatile liquid that is of significant practical interest. The method was then applied to a range of representative aziridines 2, allowing the synthesis of the corresponding compounds 6 in excellent yields scheme 4 and table 2. Synthesis of complex molecules by rearrangement reactions of epoxides.
Selected examples for the synthesis of aziridines from alkenes. A variety of stereoselective substitution reaction of epoxides and vinyl epoxides. Aziridines are highly useful compounds as building blocks for the synthesis of important organic compounds. Aziridines are organic compounds containing the aziridine functional group, a threemembered heterocycle with one amine nr and two methylene bridges cr 2. Enantioselective crosscoupling of mesoepoxides with aryl. Ring opening of nunfunctionalised nh aziridines allows direct access to aminoacid derivatives, yet the published methodology is currently limited for this transformation 1620. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Direct stereospecific synthesis of unprotected nhnme.
Request pdf aziridines and epoxides in organic synthesis synthesis of vinylepoxides vinylepoxides from unfunctionalized dienes epoxidation with. File type icon file name description size revision time user. Aziridines and epoxides in organic synthesis general monograph. Filling a gap in the literature, this clearly structured book presents the much. Epoxides are versatile intermediates in organic synthesis, but have rarely been employed in crosscoupling reactions. Aziridines and epoxides in organic synthesis sigmaaldrich. Highly regio and stereoselective ringopening of epoxides. Aziridines and epoxides in organic synthesis wiley online books.
Synthesis and ring openings of cinnamatederived nunfunctionalised aziridines tertbutyl cinnamates are aziridinated with high transselectivity by an nn ylide generated in situ from n. Asymmetric synthesis of epoxides and aziridines from aldehydes and imines varinder k. Epoxides propylene oxide are one of the most commonly used gelating agents in the solgel synthesis of metal oxide e. A general method for the synthesis of chiral nonracemic transepoxides has been developed that provides rapid access to alkyl, alkenyl, alkynyl, and phenylsubstituted transepoxides from. Metalfree onepot synthesis of 2substituted and 2,3. Aug 25, 2006 the renowned editor has succeeded in gathering together excellent authors to cover synthesis, applications, and the biological aspects in equal depth. Synthesis of nsulfonyl aziridines through regioselective opening of epoxides under solidliquid ptc conditions. 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. An easily accessible catalyst, aluminasupported copperii, efficiently catalyzes the ring opening of aziridines and epoxides followed by cyclization of the corresponding intermediate to produce a variety of functionalized 1,4benzoxazines and 1,4benzodioxanes, respectively, in one pot without any ligand in high yields.
Aziridines aziridines are the aza analogues of epoxides and are prepared by similar reactions. Aziridines are recognized as some of the most versatile synthetic intermediates in organic synthesis and for their importance in nitrogencontaining biologically active compounds. Diazocarbonyl compounds have broad applications in organic chemistry research. Aluminasupported cuii, a versatile and recyclable catalyst. View notes aziridines from nh 2 at university of pennsylvania.
Asymmetric synthesis of epoxides and aziridines from aldehydes and imines. In 1996 he took up his present position as reader in biological organic chemistry at the university of reading. Among these, the azidolysis of epoxides and aziridines. Molecules free fulltext stereoselective multicomponent. The practical stereocontrolled synthesis of vicinal. However, the enantioselective desymmetrization of meso aziridines and meso epoxides. Aziridines and epoxides in organic synthesis request pdf. Organic chemistry, arrhenius laboratory, stockholm university, 106 91 stockholm, sweden. Because of their ring strain and high reactivity, their reactions with various nucleophiles lead to high regio and stereoselective ringopening products 3,4.
The possibility of epoxides conversion into aziridines was considered. Aziridines and epoxides in organic synthesis by andrei k. Reactions of epoxides ethers are not normally susceptible to attack by nucleophiles. 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.
Nickelcatalyzed borylative ring opening of vinyl epoxides. This methodology allows for the rapid preparation of functionalized aziridines. Aziridines, the triangular, comparably highly strained nitrogen analogs of epoxides, are important synthetic intermediates i. Epoxides in complex molecule synthesis aziridines and. Palladiumcatalysed intramolecular aminations of the c. 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. 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. Although ring closure itself is quite facile, the synthesis of. Smallsized nheterocycles are important structures in organic synthesis and medicinal chemistry.
A cyclic ether in which oxygen is one atom of a threemembered ring. Aziridines and epoxides in organic synthesis yudin, andrei k. Threecomponent synthesis of highly functionalized aziridines containing a peptide side chain and their onestep transformation into. Recent advances in catalytic selective synthesis of. The utility of epoxides, for example, in the enantioselective synthesis of oxygen. The johnsoncoreychaykovsky reaction sometimes referred to as the coreychaykovsky reaction or ccr is a chemical reaction used in organic chemistry for the synthesis of epoxides, aziridines, and cyclopropanes.
Their synthetic utility lies in the fact that they can be ringopened with a broad range of nucleo. 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. Despite being labelled the ugly cousins of epoxides, 1 aziridines are valuable intermediates which undergo a variety of useful reactions, 2 most notably stereospecific and often regioselective ringopening with a variety of nucleophiles. 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.
The examples of application of azacycloalkanes in the medical and organic chemistry as biologically active substances and synthons for their preparation were. Ethylene oxide is a valuable building block for organic synthesis because each of its carbons may be converted to a functional group. The metalfree synthesis of 2substituted and 2,3disubstituted morpholines through a onepot strategy is described. Nucleophilic ringopening of epoxide and aziridine acetates.
Nucleophilic ring opening of aziridines request pdf. The examples of application of azacycloalkanes in the medical and organic. Jan 03, 2014 aziridines, the triangular, comparably highlystrained nitrogen analogues of epoxides, are important synthetic intermediates i. Besides their importance as reactive intermediates, many biologically active compounds also contain these threemembered rings. The ring opening of nh aziridines with thiols was found to proceed in good yield at room temperature in the presence of an ionic liquid1butyl3methylimidazolium chloride bmim chloride. Epoxides the epoxides are considered versatile starting materials in organic synthesis. Recent applications of aziridine ring expansion reactions in. Propylene oxide and ethylene oxide are the two epoxides that are produced in a large scale, approximately 3 and 15 tonnesyear respectively. Azacycloalkanes from epoxides and aziridines springerlink. Jun 01, 2007 epoxides 1 and aziridines 2 are the most useful synthetic intermediates in organic synthesis. A mild ring opening of vinyl epoxides and aziridines with b2pin2 catalyzed by ni0binap affords new functionalized allylic boron derivatives which undergo sequential transformations. Nucleophilic ringopening of epoxide and aziridine acetates for the stereodivergent synthesis of.
Amino acid synthesis by aziridine ring opening reaction is a good example to the use of. A highly regio and stereoselective synthesis of novel. Nucleophilic ringopening of epoxide and aziridine acetates for the. Direct conversion of epoxides into aziridines with n. Methods of preparation of azetidines, pyrrolidines, and piperidines from epoxides and aziridines were analyzed. Several routes have been developed for the syntheses of aziridines aziridination. When you see an ether in a synthesis problem, remember the williamson ether synthesis. A convenient and highyielding twostep synthesis of nsulfonyl aziridines starting from epoxides is described. Synthesis of aziridines, nucleophilic ringopening of aziridines and epoxides, organic synthesis with. The primary synthetic approaches involve either the direct aziridination of an olefin or the reaction of an imine with diazoalkanes. When ethylene reacts with oxygen under a silver catalyst, epoxide is formed. Vicinal halohydrins are useful synthetic intermediates in the synthesis of marine natural products, 1 including stereochemically complex chlorosulfolipids. Among these, the azidolysis of epoxides and aziridines are the most important for preparation of azidoalcohols 5 and azidoamines 6.
Despite being labelled the ugly cousins of epoxides, 1 aziridines are valuable intermediates which undergo a variety of useful reactions, 2 most notably stereospecific and often regioselective ring. The utility of epoxides, for example, in the enantioselective synthesis. Rethinking their application and manipulation in synthesis christopher r. Biological activities and enantioselectivity studies. Two alternative and complementary onepot procedures for the direct transformation of 2amino alcohols to ntosyl aziridines are presented. We report that bipyridineligated nickel can mediate the addition of functionalized aryl halides, a vinyl halide, and a vinyl triflate to epoxides under reducing conditions. Aziridines aziridines aziridines are the aza analogues of. Because of the strain associated with the threemembered ring, epoxides readily undergo a variety of ringopening reactions. A mild, convenient protocol for the synthesis of cisaziridines employs a catalytic amount of bronsted acid. Direct stereospecific synthesis of unprotected nh and n. Aziridines and epoxides in organic synthesis wiley. Green synthetic approaches for biologically relevant heterocycles, 2015. The uncatalyzed allylation of aldehydes allows obtaining challenging bishomoallylic alicyclic 1,3diols and 1,3amino alcohols with remarkably high stereoselectivities.
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