Intramolecular reactions Cope rearrangements

Besides intermolecular reactions, curved-arrow notation is also useful in indicating bonding changes in intramolecular reactions and rearrangement. For example, Cope-type rearrangements are seen to involve changes in three pahs of bonded electrons. 

The reaction chemistry and further synthetic application of organic compounds are of great importance and have direct relationship to the structures. 2,6-Dia-zasemibullvalene (NSBV, 6-1) features rapid intramolecular aza-Cope rearrangement and highly strained ring system. Thus, novel reaction types and different selectivity with reactions of standard aziridines arc expected, which could be also applied to the synthetic application of functionalized heterocycles [1-6]. 

TL2733,82TL2737). The reaction proceeds through an aza-Cope rearrangement of the initially formed iminium salt, followed by intramolecular cyclization. 

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... 

Entry 6 is analogous to a silyl ketene acetal rearrangement. The reactant in this case is an imide. Entry 7 is an example of PdCl2-catalyzed imidate rearrangement. Entry 8 is an example of an azonia-Cope rearrangement, with the monocylic intermediate then undergoing an intramolecular Mannich condensation. (See Section 2.2.1 for a discussion of the Mannich reaction). Entry 9 shows a thioimidate rearrangement. 

The Cope rearrangement of 24 gives 2,6,10-undecatrienyldimethylamine[28], Sativene (25j[29] and diquinane (26) have been synthesized by applying three different palladium-catalyzed reactions [oxidative cyclization of the 1,5-diene with Pd(OAc)2, intramolecular allylation of a /i-keto ester with allylic carbonate, and oxidation of terminal alkene to methyl ketone] using allyloctadienyl-dimethylamine (24) as a building block[30]. 

Although thermal [2 + 2] cycloadditions are forbidden as concerted reactions by the orbital symmetry conservation rules the same structural features which promote intermolecular cy-cioadditions will also promote intramolecular reactions. In addition, the proximity between two alkene moieties dictated by the tether length and rigidity would make these processes entropically favorable. A few reports have documented thermal intramolecular cycloadditions to cyclopropenes and activated alkenes. The thermal Cope rearrangement of allylcyclopropenes apparently proceeds by a two-step mechanism in which intramolecular [2 + 2] adducts have been observed.72-73... 

The third radical cation structure type for hexadiene systems is formed by radical cation addition without fragmentation. Two hexadiene derivatives were mentioned earlier in this review, allylcyclopropene (Sect. 4.4) [245] and dicyclopropenyl (Sect. 5.3) [369], The products formed upon electron transfer from either substrate can be rationalized via an intramolecular cycloaddition reaction which is arrested after the first step (e.g. -> 133). Recent ESR observations on the parent hexadiene system indicated the formation of a cyclohexane-1,4-diyl radical cation (141). The spectrum shows six nuclei with identical couplings of 11.9G, assigned to four axial p- and two a-protons (Fig. 29) [397-399]. The free electron spin is shared between two carbons, which may explain the blue color of the sample ( charge resonance). At temperatures above 90 K, cyclohexane-1,4-diyl radical cation is converted to that of cyclohexene thus, the ESR results do not support a radical cation Cope rearrangement. 

When the diene is acyclic, [4+4] cycloaddition remains the primary reaction pathway even when the result is a highly reactive and unstable trans-alkene product, e.g., 150 and 151 (Sch. 35). With 1,3-butadiene, these intermediates are intercepted by an additional equivalent of the diene, to give the 2 1 adducts 152 and 153. When a diene is used that cannot achieve an s-cis conformation such as 154, Diels-Alder reaction with [4+4] adducts 155 and 156 is impossible and these compounds relieve strain via Cope rearrangement to give cyclobutanes 157 and 158, respectively [98]. An intramolecular version of this reaction has been reported [99]. 

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