Cyclooctanone 0-acylation

Experimental evidence, obtained in protonation (3,6), acylation (1,4), and alkylation (1,4,7-9) reactions, always indicates a concurrence between electrophilic attack on the nitrogen atom and the -carbon atom in the enamine. Concerning the nucleophilic reactivity of the j3-carbon atom in enamines, Opitz and Griesinger (10) observed, in a study of salt formation, the following series of reactivities of the amine and carbonyl components pyrrolidine and hexamethylene imine s> piperidine > morpholine > cthyl-butylamine cyclopentanone s> cycloheptanone cyclooctanone > cyclohexanone monosubstituted acetaldehyde > disubstituted acetaldehyde. 

Indeed, cyclobutanones constitute challenging synthetic intermediates for a whole host of applications including cyclopentanone, cyclohexanone and cyclooctanone formation, olefin and diene synthesis, geminal alkylation, reductive acylation, among others,... (vide infra). 

Intramolecular Friedel-Crafts acylation provides a useful synthetic approach to cyclic ketones. The cyclization is well-suited to the preparation of six- and particularly five-membered rings, as used in key steps in routes to methyl dihydrojasmonate (equation 3), and precursors to some marine sesquiterpenes (equation 4) and the theoretically interesting spiro[4.4]nonatetraene (equation 5). Extension to cyclo-heptanones has been achieved, - but tars were formed on attempting to prepare cyclooctanones. ... 

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See also in sourсe #XX -- [ , ]

See also in sourсe #XX -- [ , ]

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