Cope isomerization

Similarly, the [3-1-4] annulation of the E- and Z-isomers of /3-hetero-substituted acryloylsilanes 52 with lithium enolates of a,-unsaturated methyl ketones 54 gave stereospecifically the c -6,7-cyclopentyl-5-trimethylsilyl-3-cycloheptenone 55 (equation 20). The stereospecificity in the annulation was explained by an anionic oxy-Cope isomerization of the 1,2-divinylcyclopropanediol intermediate 56, which was generated through the Brook isomerization of the initial 1,2-adduct (equation 20). 

The photochemical behavior of the isomeric 3-methyl-2-phenyl-2-allyl-l-azirine (66) system was also studied. Irradiation of (66) in cyclohexane gave a quantitative yield of azabicyclohexenes (67) and (68). Control experiments showed that (65) and (66) were not interconverted by a Cope reaction under the photolytic conditions. Photocycloaddition of (66) with an added dipolarophile afforded a different 1,3-dipolar cycloadduct from that obtained from (65). The thermodynamically less favored endo isomer (68b) was also formed as the exclusive product from the irradiation of azirine (66b). 

The thermal rearrangement of 1,5-dienes 1 to yield the isomeric 1,5-dienes 2, is called the Cope rearrangemenC —not to be confused with the thermolysis of amine oxides, which is also named after Arthur C. Cope. 

The aza-Cope/Mannich reaction takes advantage of the facility with which a y,<5-unsaturated itninium ion, such as 6, participates in a [3,3] sigmatropic rearrangement to give an isomeric species which is suitably functionalized for an intramolecular and irreversible Mannich cyclization (see intermediate 7). The aza-Cope rearrangement substrate 6 is simply an unsaturated iminium ion which can be fashioned in a number of ways from a homoallylic... 

The sequence depicted has been suggested as a plausible reaction mechanism. Diazabasketene primarily reacts via a retro-Diels-Alder reaction to give an azine which, after a Cope rearrangement, undergoes a further retro-Diels -Alder reaction to cleave off hydrogen cyanide. The resulting azabicyclo[4.2.0]octatriene finally isomerizes to the target molecule. 

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 ... 

The 2-azonia analog of the Cope rearrangement is estimated to be accelerated by 106, relative to the unsubstituted system.270 The product of the rearrangement is an isomeric iminium ion, which is a mild electrophile. In synthetic applications, the reaction is often designed to generate this electrophilic site in a position that can lead to a cyclization by reaction with a nucleophilic site. For example, the presence of a 4-hydroxy substituent generates an enol that can react with the iminiun ion intermediate to form a five-membered ring.271... 

The next homolog, 1,5-hexadiene (1,5-HD), is of special chemical interest because the molecule is capable of undergoing the so-called Cope rearrangement. A GED study of 1,5-HD was also recently reported6. Because of the increased conformational complexity of this molecule compared to that of 1,4-PD, the structural details of the various con-formers could not be resolved and only averaged structure parameters were determined from the gas phase. Molecules in the solid state are frozen, mostly in only one conformation, which may but must not represent the conformational ground state. Therefore, conformational isomerization is usually not discussed with X-ray structures presented in the literature. 

Most of these hydrocarbons have been prepared and their chemical behavior has been investigated. Many of them undergo mechanistically and preparatively interesting Cope-type isomerizations (see below). 

The skipped enallene 28 is easily prepared by gas-phase pyrolysis of l-hexen-5-yne (232), which under high-temperature conditions undergoes a Cope-type isomerization via transition state 233 (Scheme 5.35) [41, 92]. 

Much experimental and theoretical work has been performed with the two allenes 1,2,6-heptatriene (32) and 1,2,6,7-octatetraene (34). Thermal isomerization of 32 leads to 3-methylene-l,5-hexadiene (346), a process that at first sight looks like a typical Cope rearrangement. However, trapping experiments with either oxygen or sulfur dioxide have shown that at least half of the rearrangement passes through the diradical 345 (Scheme 5.52) [144],... 

Quaternary allenylallylammonium salts, produced in situ by prototropic isomerization of propargyl precursors (see Section 7.2.2), can undergo a 3-aza-Cope rearrangement [370]. The resulting intermediates are hydrolyzed under the reaction conditions to yield 2 -methylenepent-4-enals. 

Further examples of catalytic antibodies that are presumed to control rotational entropy are AZ-28, which catalyses an oxy-Cope [3.3]-sigmatropic rearrangement (Appendix entry 13.1) (Braisted and Schultz, 1994 Ulrich et al, 1996) and 2E4, which catalyses a peptide bond isomerization (Appendix entry 13.3) (Gibbs et al., 1992b Liotta et al., 1995). Perhaps the area for the greatest opportunity for abzymes to achieve control of rotational entropy is in the area of cationic cyclization reactions (Li et al., 1997). The achievements of the Lerner group in this area (Appendix entries 15.1-15.4) will be discussed later in this article (Section 6). 

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