Cope elimination reaction mechanisms

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). 

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... 

Sulfonium compounds (—C— SR2) undergo elimination similar to that of their ammonium counterparts (17-6 and 17-7) in scope and mechanism but this reaction is not of great synthetic importance. These syn-elimination reactions are related to the Cope elimination (17-8) and the Hofmann elimination (17-6). ... 

In the Cope elimination, thirty percent hydrogen peroxide, H2O2, is used to produce an cimine oxide, which upon heating undergoes elimination. This is a syn-elimination process. Figure 13-45 illustrates the general reaction, while Figure 13-46 shows the mechanism of the syn-elimination step. 

Oxophilic phosphomum compound 47 forms from tributylphosphine (46) and the phenylselenide 45, and this then suffers nucleophilic attack by alcohol 18. The resulting free selenium nucleophile 48 displaces phosphine oxide 50 with the formation of phenylsele-nide 51. Phenylselenide 51 is oxidi/ed by hydrogen peroxide to phenylselenoxide 52, which at room temperature undergoes an elimination reaction to (-)-A9tl2)-capnellene (1). The mechanism is similar to that of the Cope elimination, proceeding via a cyclic transition state. 

Mechanism 19-5 The Cope Elimination of an Amine Oxide 908 19-16 Reactions of Amines with Nitrous Acid 910... 

The pyrolysis of amine oxides is called Cope elimination and typically takes place at 120 °C (Scheme 6.21). The reaction is a syn periplanar elimination in which six electrons move in a five-membered ring according to a concerted, thermally induced mechanism to yield an alkene and a hydroxylamine. 

Heating the molecule shown (an amine iV-oxide) leads to an alkene in what is known as Cope elimination. Suggest a mechanism that will explain this elimination reaction and suggest a major product based on your mechanism. 

PROBLEM 18.25 Provide mechanisms for the following reactions. The first reaction (the thermal elimination of an Woxide) is called the Cope elimination, after Arthur C. Cope (1909-1966). 

Reactions in which a bond from carbon to nitrogen is broken are important in several areas of organic chemistry. The Hofmann and Cope eliminations are widely used in synthetic chemistry, and the deamination of aliphatic amines (via the nitrous acid, nitrosoamide and triazene methods) has been widely studied, usually with a primary emphasis on establishing the mechanism of the reaction. Since there has been much research activity in the latter area recently, a major fraction of the chapter is devoted to an interpretive and critical review of the deamination reactions. 

Cope, A.C., Mehta, A.S. (1%3) Mechanism of the Hofmann elimination reaction an yUde intermediate in the pyrolysis of a highly branched quaternary hydroxide. Journal of the American Chemical Society, 85, 1949-1952. 

If the reaction between cinnamate 1 and hydroxylamines occurred through a concerted mechanism, the process should take place through a cyclic (five-mem-bered ring) transition state, similar to the ones proposed for [3+2] dipolar cycloadditions or retro-Cope eliminations. The cyclic transition state for the concerted addition of deuterated iV-methylhydroxylamine to ethyl cinnamate 1 is represented in Scheme 8.7 (atoms involved in the cyclization colored blue). As the nitrogen atom and the deuterium approach the C=C bond from the same side, the addition is syn, leading to intermediate 12. A rapid proton shift would give compound 3 which can be either isolated or cyclized in the presence of a Lewis acid to the isoxazolidi-none 4 by intramolecular transesterification. The stereochemistry of the products 3 and 4 is determined during the concerted addition step. 

The bis(acetonitrile)palladium dichloride catalyzed rearrangement of R,E)-4 results in a 7 3 product distribution of 5 and 6. but a virtually complete 1.4-chirality transfer is observed (S 98 % ec)994. A possible mechanism for this type of reaction is that the palladium dichloride diene complex undergoes oxidative addition of the allylic C—C bonds to form a bis( /3-al-lyl)palladium(IV) intermediate 7 or 8, which can then reductively eliminate to give a palladium ) dichloride complex of the Cope product994 (for another mechanism see p 3572). 

An alternative pathway for the elimination of tetraalkylammonium ions is the ylide (a, jS) pathway shown in Figure 10.4. Evidence for the ylide mechanism in the reaction of 1 was reported by Cope and Mehta, who foimd that the deuterium label appeared in one of the methyl groups of trimethyl-amine (2) and not in the alkene (3, equation 10.3). ... 

This cmcial result suggested the plausible mechanism described in Scheme 4.11. Two pathways are proposed for the transformation of the product resulting from the CDC reaction of 11-A (l) either a direct Sn2 reaction or (2) a consecutive sequence with a Cope-(ype elimination then a Michael addition. 

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