Bis-reductive amination

Another route to the formation of piperidine heterocycles is cyclization via reductive amination utilizing various hydride sources. The scheme below depicts a bis reductive amination, using sodium triacetoxyborohydride as the hydride source, to generate exo- l% and endo- 19 azabicyclo[3.2.1]octane amino acids in moderate yields <06JOC8467>. 

This strategy, which involves two concomitant hydroformylation reactions of vinyl groups present on the same molecule, had never previously been used in total synthesis. Reduction of 5-azidononanedial 45h by hydro-genolysis in the presence of Pearlman s catalyst led to the formation of norlupinane, in a hydrogenolysis/bis-reductive amination tandem process, in quantitative yield (Scheme 19). This success allowed us to consider the synthesis of non-racemic mcmosubstituted quinolizidines such as (+)-lupinine and (+)-epiquinamide. 

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