1.3‐Dipolare Cycloadditionen, LVI. Eine bequeme Synthese von N‐substituierten Pyrrolen aus mesoionischen Oxazolonen und Alkinen
TL;DR: In this paper, a convenient synthesis of N-substituted Pyrroles from Mesoionic Oxazolones and Alkynes has been presented, which can be used for cycloadditions if one treats them with acetic anhydride in the presence of suitable acetylenic dipolarophiles.
Abstract: 3-Methyl-2.4-diphenyl-oxazolium-5-oxid (2) vereinigt sich bei 0−130° mit Alkinen (Acetylen und Alkylderivate, phenylierte und acylierte Acetylene, Acetylen-carbonsaureester) unter Kohlendioxid-Abgabe zu den Pyrrolen 3, 5–13. Zahlreiche N-Acyl-sek.-aminosauren, bei denen die Isolierung des Oxazolium-5-oxids nicht gelingt, lassen sich in situ an Alkine zu den Pyrrol-Abkommlingen (20–28, 33–36, 38, 39) cycloaddieren, wenn man mit Acetanhydrid in Gegenwart des Dipolarophils behandelt. Die Additionsrichtung wird weniger von den Substituenten als von der Natur des Oxazolium-5-oxid-Rings bestimmt.
1,3-Dipolar Cycloadditions, LVI. A Convenient Synthesis of N-Substituted Pyrroles from Mesoionic Oxazolones and Alkynes
3-Methyl-2,4-diphenyl-oxazolium 5-oxide (2) combines at 0−130° with alkynes (acetylene and 1-alkynes, phenylated and acylated acetylenes, acetylenecarboxylic esters) to give initially adducts which then eliminate carbon dioxide to form the pyrroles 3, 5–13. Numerous N-acyl sec-amino acids which do not allow the isolation of oxazolium 5-oxides on anhydrization, can be utilized for cycloadditions if one treats them with acetic anhydride in the presence of suitable acetylenic dipolarophiles. The pyrroles 20–28, 33–36, 38, 39 have been prepared by this method. The direction of cycloaddition is determined mainly by the nature of the oxazolium 5-oxide ring rather than by the substituents in the 2- and 4-position.
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TL;DR: This review aims to describe the background and mechanisms of azomethine ylide formation and intramolecular cycloaddition, giving a critical account including the very first example and covering to early 2005.
Abstract: It was in 1963 that Huisgen laid out the classification of 1,3-dipoles and the concepts for 1,3-dipolar cycloaddition reactions, although it was not until 1976 that the first intramolecular 1,3-dipolar cycloaddition reaction of an azomethine ylide was reported. Since then, impressive developments have been described in this area, with the establishment of various useful methods for the formation of azomethine ylides and the determination of the requirements for a successful intramolecular cycloaddition reaction. Use of this methodology for the synthesis of pyrrolidineand pyrrole-containing natural products has been expanding rapidly. This review aims to describe the background and mechanisms of azomethine ylide formation and intramolecular cycloaddition, giving a critical account including the very first example and covering to early 2005. It is hoped that this review will be a useful resource for chemists interested in cycloaddition reactions and will inspire further exciting developments in this area. Cycloaddition reactions are one of the most important class of reactions in synthetic chemistry. Within * Corresponding author. Tel: +44 (0)114 222 9428. Fax: +44 (0)114 222 9346. E-mail: i.coldham@sheffield.ac.uk. † University of Sheffield. ‡ Tripos Discovery Research Ltd. Iain Coldham (b. 1965) is a Reader in Organic Chemistry at the University of Sheffield. He obtained his undergraduate degree and Ph.D. from the University of Cambridge, completing his Ph.D. in 1989 under the supervision of Stuart Warren. After postdoctoral studies at the University of Texas with Philip Magnus, he joined the staff in 1991 at the University of Exeter, U.K. In 2003, he moved to the University of Sheffield where he is involved in research on chiral organolithium compounds and on dipolar cycloaddition reactions in synthetic organic chemistry.
863 citations
TL;DR: In this article, a synthese traitant du classement de ces composes et de leurs reactions de cycloaddition is described, based on a syntactique traitant.
274 citations
TL;DR: This review provides an overview of the synthetic chemistry that has been utilised to prepare natural products containing a pyrrolic ring.
250 citations
TL;DR: This tutorial review aims to summarize some of the more recent applications of oxazolones as a general template for the stereoselective syntheses of amino acids and heterocyclic scaffolds.
Abstract: The assembly of structurally diverse scaffolds via substrate controlled diversity oriented synthesis (DOS) has proven to be an effective tool in the discovery of novel biologically important compounds. This tutorial review aims to summarize some of the more recent applications of oxazolones as a general template for the stereoselective syntheses of amino acids and heterocyclic scaffolds. A brief introduction covers a short history, nomenclature and general reactivity of oxazolones. The main body of this tutorial review highlights several applications of oxazolones as starting blocks for the diverse and stereoselective synthesis of amino acids, oxazoles, β-lactams, pyrroles, imidazolines, pyrrolines, and imidazoles.
219 citations
01 Jan 1991
TL;DR: The 1,3-dipolar cycloaddition as discussed by the authors is a well-known 1, 3-dipole-based method for 5-membered heterocyclic ring synthesis.
Abstract: Cycloaddition reactions have figured prominently in both synthetic and mechanistic organic chemistry.1,2 Current understanding of the underlying principles in this area has grown from a fruitful interplay between theory and experiment.3 The monumental work of Huisgen and coworkers in the early 1960s led to the general concept of 1,3-dipolar cycloaddition.4–7 Few reactions rival this process in the number of bonds that undergo transformation during the reaction, producing products considerably more complex than the reactants. Over the years this reaction has developed into a generally useful method of five-membered heterocyclic ring synthesis, since many 1,3-dipolar species are readily available and react with a wide variety of dipolarophiles. 1,3-Dipolar cycloadditions are bimolecular in nature and involve the addition of a 1,3-dipole (1) to a multiple π-bond system (2) leading to five-membered heterocycles (3; equation 1).
158 citations
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112 citations
TL;DR: In this article, the synthesis and spectral properties of 3-methyl-2,4-diaryloxazolium 5-oxides (2, 16-21) are described.
Abstract: Die Synthese und die spektralen Eigenschaften sydnon-analoger 3-Methyl-2.4-diaryl-oxazolium-5-oxide (2, 16–21) werden beschrieben. Die Thermolyse von 2 fuhrt zu einem tetra-substituierten Allen, das vielleicht durch Dimerisation eines mit 2 valenztautomeren Ketens (28) und Kohlendioxid-Abspaltung gebildet wird. Bei der Offnung des Oxazolium-oxid-Ringes mit Verbindungen HX greift das Nucleophil an der Carbonylgruppe an. Auch uber den Verlauf der Autoxydation von 2 werden Aufschlusse erzielt.
Preparation and Properties of Mesoionic Oxazolones
Synthesis and spectral properties of 3-methyl-2,4-diaryloxazolium 5-oxides (2, 16–21) are described. The thermolysis of 2 affords a tetrasubstituted allene; possibly this is the result of a dimerization of the ketene 28 which is a valence tautomer of 2, and elimination of carbon dioxide. In the ring opening of oxazolium 5-oxides with compounds HX the nucleophile attacks the carbonyl group. Also the course of autoxidation of 2 was investigated.
78 citations
TL;DR: In this paper, die Variationsbreite dieser neuen, praparativ einfach auszufuhrenden Pyrazol-Synthese.
Abstract: Als cyclischen Azomethin-imine gehen die Sydnone 1.3-Cycloadditionen an CC-Dreifachbindungen ein; rasche CO2-Abgabe fuhrt zu Pyrazolen. 36 Beispiele zeigen die Variationsbreite dieser neuen, praparativ einfach auszufuhrenden Pyrazol-Synthese. Fallende dipolarophile Aktivitat wird in der Folge Acetylencarbonester und -ketone, phenylierte Acetylene, nichtkonjugierte Alkine beobachtet.
72 citations
TL;DR: In this paper, Azlactone with different substituents R and R′ can add in two directions, and azlactones with verschiedenen Substituenten R und R′ konnen sich in zwei Richtungen addieren.
Abstract: Aromatisch substituierte Δ2-Oxazolinone-(5) (Azlactone) reagieren uber die tautomeren Oxazolium-5-oxide mit Acetylendicarbonsaure-dimethylester zu Pyrrol-dicarbonsaure-(34)-dimethylestern Es ist vorteilhaft, die Azlactone aus N-Acyl-aminosauren mit Acetanhydrid in Gegenwart des Dipolarophils zu erzeugen Der in situ-Cycloaddition der Dialkyl-ox-azolinone-(5) schliest sich eine nucleophile NH-Addition der gebildeten Pyrrole an eine zweite Molekel Acetylendicarbonsaureester an Eine Reihe von α-Aminosauren wird in solche 1 : 2-Produkte ubergefuhrt — Auch die Additionen an Propiolsaure-methylester verlaufen glatt; Azlactone mit verschiedenen Substituenten R und R′ konnen sich in zwei Richtungen addieren
1,3-Dipolar Cycloadditions, LIV Synthesis of Pyrroles from Azlactones and Acetylene Carboxylic Esters
Δ2-Oxazolin-5-ones (azlactones) with aromatic substituents react via the tautomeric ox-azolium 5-oxides with dimethyl acetylenedicarboxylate to give pyrrole-3,4-dicarboxylates It is advantageous to prepare the azlactones in situ from N-acylamino acids and acetic anhydride in the presence of the dipolarophile In the corresponding in situ reaction of dialkyl-oxazolinones the formation of the substituted pyrrole is followed by a nucleophilic attack of the pyrrole-N on a second molecule of the acetylenedicarboxylate Numerous amino acids are converted by this procedure into such 1 : 2-products - Additions to methyl pro-piolate occur equally smoothly; azlactones with different substituents R and R′ can add in two directions
65 citations