Hiroki Yamagishi, David W. Small, Richmond Sarpong
High Resolution Image Download MS PowerPoint Slide 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 ( 4 ), an isomer of calycanthine ( 1 ), which was achieved in 9 steps and set the stage for the preparation of calycanthine ( 1 ), chimonanthine ( 2 ), and psychotriadine ( 6 ). Our studies, driven by calculations, also provide the first access to a natural product bearing the pyrrolidinoquinoline scaffold, CPC-2 ( 29 ). Finally, we resolve a long-standing misassignment of the structure of the natural product dubbed isocalycanthine. En route to our synthesis of 4, 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.