1, 6-Dihydro-3 (2H)-pyridinones. II. Synthesis of 2-Azabicyclo [2. 2. 2] octanes by the Reaction of N-Substituted 1, 6-Dihydro-3 (2H)-pyridinones with 1, 3-Dicarbonyl Compounds

Abstract

Base-catalyzed reaction of N-substituted 1, 6-dihydro-3 (2H)-pyridinones (1 and 2) with some 1, 3-dicarbonyl compounds (8a-e) resulted in exclusive formation of the 2-azabicyclo [2. 2. 2] octan-7-ones (5 and 6), while a similar treatment of 1 with dimethyl acetonedicarboxylate (8f) gave the 3-azabicyclo [3. 3. 1] nonan-7-one (10f) as a sole product. On deethoxycarbonylation under acidic conditions, the azabicyclooctanecarboxylates (5a, 5c, 6a, and 6c) afforded the 3-azabicyclo [3. 3. 1] nonanes (13 and 16) and/or the 2-azabicyclo [2. 2. 2] octanes (14, 15, 17, and 18). On the other hand, ketalization of a mixture of 17 and 18 with ethylene glycol provided the diketal (23), which was derived into the monoketone (24) upon treatment with 98% formic acid. Haloform reaction of 24 followed by esterification yielded the ester (26), which was transformed into the aldehyde (28) by sodium borohydride reduction and subsequent PCC oxidation. An acidic hydrolysis of 28 directly furnished the desired 2-azabicyclo [2. 2. 2] octanone derivative (7), a possible synthon for the Iboga alkaloids.