Enantioselective route to an AE-ring intermediate in the total synthesis of talatisamine

Talatisamine [(-)-1] is a C19-diterpenoid alkaloid with an intricately fused ABCDEF-ring system. In 2020, we reported a total synthesis of racemic talatisamine [(+/-)-1], in which AE-ring fragment (+/-)-5-alpha/5-beta was utilized as the pivotal early-stage intermediate. Herein, we disclose the development of an enantioselective route to (-)-5-beta for the total synthesis of (-)-1. Enantioselective intermolecular Mannich, Lewis acid-mediated intramolecular Mannich, and reductive N-ethylation reactions were employed as the three key transformations.