Enamino ester reduction:: A short enantioselective route to pyrrolizidine and indolizidine alkaloids.: Synthesis of (+)-laburnine, (+)-tashiromine, and (-)-isoretronecanol

Various chiral pyrrolidine tetrasubstituted beta-enamino esters were reduced catalytically or chemically with good to moderate diastereoselectivity owing to a chiral induction originated from (S)-alpha-methylbenzylamine. With endocyclic double bond compounds, the best result was obtained using PtO2 as hydrogenation catalyst and led to a major syn addition product (e.d. 90%). In the case of exocyclic double bond compounds, hydrogenation over Pd/C gave rise to the higher diastereoselectivity and mainly afforded the unexpected anti addition product (e.d. 84%). The scope of these reductions has been extended to the synthesis of three pyrrolizidine or indolizidine alkaloids: (+)-tashiromine, (+)-laburnine, and (-)-isoretronecanol. Syntheses of these natural products, starting from chiral beta-enamino diesters, were achieved in a short and convenient manner, leading to enantiopure compounds in good overall yields.