Rearrangement oxygen-nucleophiles

Anomalous Fischer cyclizations are observed with certain c-substituted aryl-hydrazones, especially 2-alkoxy derivatives[l]. The products which are formed can generally be accounted for by an intermediate which w ould be formed by (ip50-substitution during the sigmatropic rearrangement step. Nucleophiles from the reaction medium, e.g. Cl or the solvent, are introduced at the 5-and/or 6-position of the indole ring. Even carbon nucleophiles, e.g. ethyl acetoacelate, can be incorporated if added to the reaction solution[2]. The use of 2-tosyloxy or 2-trifluoromethanesulfonyloxy derivatives has been found to avoid this complication and has proved useful in the preparation of 7-oxygen-ated indoles[3]. 

Ruonne atoms in aromatic nitrogen heterocycles are readily replaced by oxygen nucleophiles [77] Bistnfluoromethyl hydroxylarmne anion is an mterest-ing nucleophile for the mtroduction of oxygen mto perfluoropyndine Rearrangement of the product occurs at 125 °C [18] (equation 12)... 

The most intense interest in the addition of oxygen nucleophiles to Tr-allylpalladium complexes has centered on the delivery of OAc. For example, in allylpalladium-OAc complexes, acetate can be induced to migrate to the allyl ligand by the addition of CO (equation 46).162-164 Rearrangements and isomerizations of allyl acetates can also be readily accomplished via Pd catalysis (equations 47 and... 

Amine nucleophiles appear generally to add by attack at the allyl ligand. Similar to oxygen nucleophiles, however, a caveat must be noted in evaluating the observed regioselectivities in that the allyl amine products are capable of rearrangement by reentry into the ir-allyl manifold. 

The oxygen nucleophile may be that of a peroxy acid such as perbenzoic acid. In this case a rearrangement may occur under acidic conditions. This takes place with the expulsion of benzoate and the insertion of an oxygen adjacent to the carbonyl group. The reaction, known as the Baeyer-Villiger rearrangement leads to the conversion of a ketone to an ester (Scheme 3.43) or a cyclic ketone to a lactone (cyclic ester). 

Cyclic 1,2-diketones, such as3-methylcyclopentane-l,2-dione, act as oxygen nucleophiles in palladium(0)-catalyzed reactions with a range of cyclic and acyclic allylic esters. The products of these reactions were subjected to a lanthanide-catalyzed Claisen rearrangement to access the C-alkylated products. 

Reference is in general made to . One example from the early 1990s is provided by the rearrangement of pyrazoles to pyrimidines, which can be effected under mild conditions, pH about 9, and room temperature, by the addition of an oxygen nucleophile to an exocyclic double bond (580) (Scheme 92). The intermediate betaine (581) subsequently suffers ring expansion with formation of 1,2-dihydropyrimidines (582) <92JOC4i5l>. 

The second set of examples involves the use of thionium ions as electrophiles in inter- and intramolecular processes to obtain a-substituted sulfides (see 24 25, Scheme 20.7T which is the most common type of Pummerer reaction. Applications of this classical Pummerer rearrangement are exemplified in the synthesis of trans-solamin, the synthesis of indolizidine alkaloids, and the synthesis of the CDE ring of erinacine E. The first exanple fScheme 20.10 uses Pummerer chemistry in the generation of a thionium ion, which reacts in an intermolecular tin-mediated ene reaction the second one fScheme 20.11 uses Pummerer chemistry to introduce a nitrogen-containing heterocycle by intramolecular addition to form the coniceine core and the third example fScheme 20.12 is an intramolecular silicon-induced Pummerer reaction with oxygenated nucleophiles applied to the synthesis of a precursor of erinacine. Details of these Pummerer-based strategies are discussed below. 

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