Synthesis and transformations of 6,6,7,7-tetramethyl-2-quinuclidone

Chemistry of Bridged Lactams and Related Heterocycles

“…256,257 Although these values are consistent with the high basicity of the amide nitrogen in this [2.2.2] ring system, methyl-substituted 2-quinuclidones did not succeed as good models for reactivity of bridged lactams due to steric hindrance around amide bonds.…”

“…253–257 The potential products resulting from the cleavage of C–NC(O) bonds were not observed in these systems.…”

“…More recently, Greenberg optimized the conditions for preparation of 6,6,7,7-tetramethyl-2-quinuclidone 46c (Scheme 6). 259 It was found that the previously published method for the synthesis of qunuclidone 46c 256,257 gives almost exclusively polymeric material. Using high dilution techniques, the highly-strained lactam 46c was obtained in modest yield.…”

“…Thus, Yakhontov reported cleavage reactions of the C–NC(O) bond in the tetramethyl-substituted 2-quinuclidone using PhLi, PCl 5 and acetone cyanohydrin (Scheme 124). 256,257 The nucleophile had a pronounced effect on the reaction outcome (cf. Table 14).…”

“…256,257 The resulting piperidines were isolated in good yields after the basic workup. Yakhontov also observed an unexpected transacylation of the twisted amide bond during reduction of the sterically-hindered 2-quinuclidone 46c with LiAlH 4 (Scheme 129).…”