Cope elimination reaction

Amine oxides 2, which can be prepared by oxidation of amines 1, react upon heating to yield an olefin 3 and a hydroxylamine 4. This reaction is called the Cope elimination reaction,and as a synthetic method is a valuable alternative to the Hofmann degradation reaction of quaternary ammonium salts. 

Certain amine oxides, especially those derived from six-membered heterocyclic amines e.g. N-methylpiperidine oxide, that cannot go through a planar, five-membered transition state, do not undergo the Cope elimination reaction. 

In addition to being a valuable method for the preparation of olefins, the Cope elimination reaction also gives access to iV,A -disubstituted hydroxylamines. 

When 1,5-dienes are heated, they isomerize, in a [3,3] sigmatropic rearrangement known as the Cope rearrangement (not to be confused with the Cope elimination reaction, 17-8)When the diene is symmetrical about the 3,4 bond, we have the unusual situation where a reaction gives a product identical with the starting material ... 

In order to study the mechanism of reverse Cope elimination reactions in the condensation of pentenal and hexenal with iV-methylhydroxylamine. it seemed reasonable to synthesize unsaturated nitrones (226). 

This reaction sequence illustrates how the rates of many base-catalyzed reactions can be enhanced greatly by substitution of dimethylsulfoxide for the usual hydroxylic solvents. Other examples of the enhanced reactivity of anions in dimethylsulfoxide are found in Wolff-Kishner reductions and Cope elimination reactions. The present reaction illustrates the generation of an aryne intermediate from bromobenzene. ... 

Cope, A. C. Foster, T. T. Towle, P. H. J. Am. Chem. Soc. 1949, 71, 3929. Arthur Clay Cope (1909-1966) was born in Dunreith, Indiana. He was a professor at MIT when he discovered the Cope elimination reaction and the Cope rearrangement. The Arthur Cope Award is a prestigious award in organic chemistry from the American Chemical Society. 

Cope elimination reactions of threo- and entf/zro-A, Ai-dimethyl-3-phenyl-2-butyl-amine oxide have been investigated using QM/MM calculations in water, THF, and DMSO.8 The aprotic solvents provided rate accelerations of up to 106-fold. It has been found that the amine oxide oxygen is the acceptor of three hydrogen bonds from water molecules for the reactant but only one or two weaker ones at the transition state. 

Umezawa and co-workers9 have reported a new synthesis of the tetracyclic lactam (19), which is a key intermediate in Torssell s synthesis of lycorine (cf. Vol. 9, p. 139) the Japanese work (Scheme 2), therefore, represents a formal synthesis of the alkaloid. The cyclohexyl isocyanate (15) (trans-diequatorial aryl and isocyanate groups) cyclized to a tricyclic lactam, which by reduction with a hydride and hydrolysis gave the ketone (18). The tetracyclic ketone (16) was converted into the 2,3-ene (17) by a Cope elimination reaction, and the synthesis of compound (19) was completed by transposition of the lactam carbonyl group from C-5 to C-7. 

The intramolecular nitrone-alkene cycloaddition reaction of monocyclic 2-azetidinone-tethered alkenyl(alkynyl) aldehydes 211, 214, and 216 with Ar-aIkylhydroxylamincs has been developed as an efficient route to prepare carbacepham derivatives 212, 215, and 217, respectively (Scheme 40). Bridged cycloadducts 212 were further transformed into l-amino-3-hydroxy carbacephams 213 by treatment with Zn in aqueous acetic acid at 75 °C. The aziridine carbaldehyde 217 may arise from thermal sigmatropic rearrangement. However, formation of compound 215 should be explained as the result of a formal reverse-Cope elimination reaction of the intermediate ct-hydroxy-hydroxylamine C1999TL5391, 2000TL1647, 2005EJ01680>. 

Almost all evidence indicates that the transition state must be planar. Deviations from planarity as in 17-4 (see p. 1507) are not found here, and indeed this is why six-membered heterocyclic nitrogen compounds do not react. Because of the stereoselectivity of this reaction and the lack of rearrangement of the products, it is useful for the formation of trans-cycloalkenes (eight-membered and higher). A polymer-bound Cope elimination reaction has been reported. ... 

Pyrolysis of Amine Oxides The Cope Elimination Reaction ... 

Ciganek, E. Reverse Cope elimination reactions. 2. Application to synthesis. J. Org. Chem. 1995, 60, 5803-5807. 

Cope elimination reaction. Formation of an olefin and a hydroxylamine by pyrolysis of an amine oxide. 

Pyrolysis of the oxide of tertiary amine 1 yields olefin 2 and hydroxylamine 3. This olefination method is known as the Cope elimination reaction.1-3... 

As the name suggests, the reverse Cope elimination reaction involves formation of a tertiary amine oxide from a hydroxylamine and olefin.17,18 For example, reaction of N-methylhydroxylamine (49) with 2,2-diphenyl-4-pentenal (50) in ethanol at room temperature gave amine oxide 51 in 51% yield, together with the expected nitrone 52. It has been suggested the mechanism of the reverse Cope reaction could be a radical chain reaction19,20 however, more recent studies have confirmed the mechanism is analogous to the concerted Cope elimination.17... 

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