Concise Total Syntheses of (<i>−</i>)-Crinipellins A and B Enabled by a Controlled Cargill Rearrangement
Bo Xu, Ziyao Zhang, Dean J. Tantillo, Mingji Dai
Abstract
High Resolution Image Download MS PowerPoint Slide Herein, we report concise total syntheses of diterpene natural products (−)-crinipellins A and B with a tetraquinane skeleton, three adjacent all-carbon quaternary centers, and multiple oxygenated and labile functional groups. Our synthesis features a convergent Kozikowski β-alkylation to unite two readily available building blocks with all the required carbon atoms, an intramolecular photochemical [2 + 2] cycloaddition to install three challenging and adjacent all-carbon quaternary centers and a 5–6–4–5 tetracyclic skeleton, and a controlled Cargill rearrangement to rearrange the 5–6–4–5 tetracyclic skeleton to the desired tetraquinane skeleton. These strategically enabling transformations allowed us to complete total syntheses of (−)-crinipellins A and B in 12 and 13 steps, respectively. The results of quantum chemical computations revealed that the Bronsted acid-catalyzed Cargill rearrangements likely involve stepwise paths to products and the AlR 3 -catalyzed Cargill rearrangements likely involve a concerted path with asynchronous alkyl shifting events to form the desired product.