Taming Radical Pairs in the Crystalline Solid State: Discovery and Total Synthesis of Psychotriadine
Jordan J. Dotson, Ieva Liepuoniute, J. Logan Bachman, Vince M. Hipwell, Saeed I. Khan, K. N. Houk, Neil K. Garg, Miguel A. Garcı́a-Garibay
Abstract
Solid-state photodecarbonylation is an attractive but underutilized methodology to forge hindered C–C bonds in complex molecules. This study discloses the use of this reaction to assemble the vicinal quaternary stereocenter motif present in bis(cyclotryptamine) alkaloids. Our strategy was enabled by experimental and computational investigations of the role of substrate conformation on the success or failure of the solid-state photodecarbonylation reaction. This informed a crystal engineering strategy to optimize the key step of the total synthesis. Ultimately, this endeavor culminated in the successful synthesis of the bis(cyclotryptamine) alkaloid “psychotriadine,” which features the elusive piperidinoindoline framework. Psychotriadine, a previously unknown compound, was identified in the extracts of the flower Psychotria colorata, suggesting it is a naturally occurring metabolite.