Synthesis of Indolizines as Illustrated in Alkaloid Construction

Significance

A short and efficient synthesis of the alkaloid tashiromine is presented in which an intramolecular acyl imminium-allyl silane condensation plays a key role to form an indolizine heterocycle. Thus, a cross-metathesis initiates the total synthesis to give the succinimide 1 which, upon partial reduction and treatment with TFA, undergoes an intramolecular cyclization via 2 to give the indolizinone 3 in high yield and diastereoselectivity. Simple two-step oxidative unmasking with in situ reduction to the primary alcohol followed by lactam reduction gives tashiromine in 19% overall yield starting from succinimide (six steps).