The CSIC [carbanion mediated sulfonate (sulfonamido) intramolecular cyclization] reaction: Scope and limitations

Article abstract of DOI:10.1016/S0040-4020(99)00379-8

The CSIC (Carbanion-mediated Sulfonate-Sulfonamide-Intramolecular Cyclization) reaction has been extended to new carbonyl containing substrates, showing the scope and limitations of this process. Suitable derivatives of ketones (e.g acetophenone (1)), β-keto esters (e.g ethyl acetoacetate (4)), γ-keto esters (e.g ethyl 2-oxocyclohexaneacetate (5) and ethyl levulinate (6)) proved reluctant to undergo this protocol. Cyclopropyl methyl ketone (2) gave the heterocycle (3), only in the 'sulfonamide' synthetic sequence of the CSIC reaction. Cyclic azaketones (e.g tropinone (7)) fated also, but 4-piperidones (9, 10) afforded the novel 3,8- disubstituted 4-amino-8-aza-1-oxa-2-thiaspiro[4.5]dec-3-ene 2,2-dioxide (12, 15a-c) and 8-substituted 4-amino-1,8-diaza-2-thiaspiro[4.5]dec-3-ene 2,2- dioxide (18a, 18b, 21a, 21b) ring systems; the former compounds are the first examples of such ring systems substituted at the 3-position, whereas the latter represent the first ever representatives of spiro fused systems containing the 4-amino-2,3-dihydroisothiazole 1,1-dioxide moiety. Base promoted (NaH or DBU) cyclization of precursors 11b, 14a-c, 17b, 17c and 20 give the final adducts in good overall yield. Finally, we were unsuccessful with some conveniently functionalized anthranilonitrile derivatives (8a-d), in an attempt to extend the CSIC reaction to β-aminonitriles. As a result of these studies the substrate dependent reactivity in the CSIC reaction has been analyzed in depth and some restrictions and limitations have been observed and discussed.