Unified Total Synthesis of <i>C</i> ₂ -Symmetric Bis(cyclotryptamine) Alkaloids Utilizing a Single-Atom Insertion/Deletion Strategy

Strategies for total synthesis have advanced alongside the development of new methodologies, thereby enabling access to structurally intricate molecules that were previously difficult to obtain. Here, we present a strategy for the synthesis of bis(cyclotryptamine) alkaloids inspired by methods for single-atom insertion/deletion. To implement our plan, we first pursued the synthesis of tetrahydropsychotriadine (<b>4</b>), an isomer of calycanthine (<b>1</b>), which was achieved in 9 steps and set the stage for the preparation of calycanthine (<b>1</b>), chimonanthine (<b>2</b>), and psychotriadine (<b>6</b>). Our studies, driven by calculations, also provide the first access to a natural product bearing the pyrrolidinoquinoline scaffold, CPC-2 (<b>29</b>). Finally, we resolve a long-standing misassignment of the structure of the natural product dubbed isocalycanthine. En route to our synthesis of <b>4</b>, we establish a methodology for the construction of unprecedented diaryl-substituted cis- and trans-fused 5,5-bicycles using a photodecarbonylation. The mechanism for the trans-selective formation of 5,5-bicycles is investigated by using DFT calculations.