Nucleophilic substitution oxygen nucleophile cyclization

It was reported (94IC415) that the reactions of 2,2,3,3 tetrafluorobutyleneglycol triethylsilyl ether with 1,4-dibromotetrafluorobenzene, tetrabromoethane, and oxalyl fluoride form oxygen-containing heterocycles (Scheme 143). Adamson et al. (92JFC(58)300) showed that 1,2,3,4-tetrafluoroacridines 154 are formed in quantitative yields in reactions of pentafluorobenzaldehyde with substituted anilines at room temperature (Scheme 144). 2,3-Diphenyl-4,5,6,7-tetrafluorobenzofuran is formed in a reaction of hexafluorobenzene with phenyl benzyl ketone in the presence of sodium hydride (79BCJ2657) (Scheme 145). The reaction involves intramolecular nucleophilic cyclization of the generated O-nucleophile due to tautomerization of the intermediate ketone. 

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]. 

As mentioned earlier, the McDonald group was able to extend their epoxide-domino-cyclization strategy to 1,5,9-triepoxides [10]. Indeed, they were successful in converting precursor 1-143 into the tricyclic product 1-146 in 52 % yield after hydrolysis (Scheme 1.36) [41]. As a possible mechanism of this polyoxacyclization it can be assumed that, after activation of the terminal epoxide by BF3, a sequence of intramolecular nucleophilic substitutions by the other epoxide oxygens takes place, which is induced by a nucleophilic attack of the carbonate oxygen, as indicated in 1-144 to give 1-145. 

In summary, it would appear that the oxidation of a catecholamine probably first involves the formation of a semi-quinone radical (this can be brought about by an one-electron transfer, e.g. from Cu++ ions,14 or by photoactivation 1) which rapidly undergoes further oxidation (e.g. with atmospheric oxygen) to an intermediate open-chain quinone (such as adrenaline-quinone) and then cyclizes by an oxidative nucleophilic intramolecular substitution to the amino-chrome molecule. Whilst the initial formation of a leucoaminochrome by non-oxidative cyclization of the intermediate open-chain quinone in some cases cannot be entirely excluded at the moment (cf. Raper s original scheme for aminochrome formation72), the... 

The topic of nucleophilic attack at an sp2 carbon would be too wide a field to review in one chapter, if one were to discuss all facets and outcomes, some of which are shown in Figure 1. If the nucleophile is anionic an anion is formed, but if the nucleophile is neutral a zwitterion is produced. If X is oxygen or nitrogen, then the outcome can be carbonyl addition, substitution or a Darzens-type reaction. If the X is another carbon then addition leads to conjugate additions or polymerization. Alternatively the nucleophile could be expelled after rotation about the C—C bond to give overall isomerization. Both substitution and cyclization are also observed. 

Aryl radical cations generated by electron-transfer processes from methoxy substituted arenes to DCN, tethered by oxygen, nitrogen as well as carbon nucleophile leads to intramolecular cyclizations (Scheme 8.67). The synthetic potentials of... 

FJectrophile-promoted cyclization of unsaturated amides results in the formation of substituted lactones. The key step of the reaction is attack on the electrophile-activated double bond by the more nucleophilic oxygen of the bidentate function group, followed by hydrolysis of the imido derivative. 

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