A highly stereocontrolled, four-step synthesis of (±)-lasubine II

Article abstract of DOI:10.1021/ja00230a026

A four-step synthesis of (±)-lasubine II (1) from 4-methoxypyridine is described. The addition of benzyl chloroformate to a mixture of (3,4-dimethoxyphenyl)magnesium bromide and 4-methoxypyridine gives the N-acetyl-2,3-dihydro-4-pyridone 3 on workup with aqueous acid. Copper-mediated conjugate addition of (4-chlorobutyl)magnesium bromide to 3 affords cis-2,6-disubstituted piperidine 6. Catalytic hydrogenolysis of 6 with palladium on carbon in the presence of lithium carbonate gives an 82% yield of quinolizidinone 7. Reduction of 7 with lithium trisiamylborohydride provides (±)-lasubine II (1). The four-step total synthesis is carried out in 28% overall yield with excellent stereocontrol.