Enantioselective Total Synthesis and Absolute Configuration Assignment of (+)‐Tronocarpine Enabled by an Asymmetric Michael/Aldol Reaction

We present the first asymmetric total synthesis and absolute configuration determination of (+)‐tronocarpine. The [6.5.7.6.6] pentacyclic core was constructed at an early stage by using a sequential cyclization strategy through a newly developed catalytic asymmetric Michael/aldol cascade to build the aza[3.3.1]‐bridged cycle and a tandem reduction/hemiamidation procedure to assemble the seven‐membered lactam. The side‐chain functionalities were incorporated at a late stage by several appropriately orchestrated manipulations under mild conditions. The synthesis of enantiomerically pure (+)‐tronocarpine was achieved through a 20‐step longest linear sequence from tryptamine. Bright and early: The [6.5.7.6.6] pentacyclic core was constructed at an early stage of the synthesis of tronocarpine (see scheme; NPhth=phthalimido) by using a newly devised catalytic asymmetric Michael/aldol cascade to build the aza[3.3.1]‐bridged ring system and a tandem reduction/hemiamidation procedure to assemble the seven‐membered lactam. Other functionalities were incorporated at a later stage under mild conditions.