Total Synthesis of (−)-Xishacorene B from (R)-Carvone Using a C–C Activation Strategy

Abstract

The activation of C-C bonds that are traditionally viewed as unreactive, when coupled with other bond-forming processes, can offer new approaches to the synthesis of complex molecular scaffolds. In this Communication, we demonstrate the conversion of carvone to unusual bicyclo[3.3.1] and [3.2.1] frameworks by exploiting a Pd(0)-catalyzed C-C bond activation reaction and a radical cyclization process. This sequence is applied to a 10-step synthesis of the diterpene xishacorene B.

4‐Methyltetrahydropyran (4‐MeTHP): Application as an Organic Reaction Solvent

“…Initially we set out to test radical reaction compatibilities, as it is expected the six‐membered THP derivatives would be more stable to autooxidation as compared to five‐membered THF derivatives . Indeed, a selection of radical reactions in laboratory experiments are still occasionally carried out in carcinogenic benzene, a solvent in great need of replacement in view of the health hazards. As representative examples, tin or silicon radical‐mediated additions, reductions, and cyclizations were carried out in 4‐MeTHP (Scheme ).…”

Transition Metal‐Mediated C−C Single Bond Cleavage: Making the Cut in Total Synthesis

“…In addition to their work on the phomactins,Sarpong and co-workers showcased the utility of C À Cb ond cleavage in 2018 with the first total synthesis of xishacorene B( 34; Scheme 6A). [25] Thex ishacorene diterpenes,h ydrocarbon natural products first isolated in 2017 from the soft coral Sinularia polydactyla off the coast of China, [26] exhibit immunopotentiating activity and contain au nique bicyclo-[3.3.1]nonane core.R etrosynthetically,x ishacorene Bc ould arise from triol 35,w hich in turn could be constructed from cyclohexenone 36 through ar adical cyclization,w ith the reactive enone serving as ar adical acceptor.T his cyclohexenone was proposed to arise from cyclobutanol 37 and vinyl iodide 38 through aP d-catalyzed CÀCb ond-cleavage/ cross-coupling reaction. Cyclobutanol 37 was synthesized in two steps from (R)-carvone following Bermejosprocedure [24] (Scheme 5; 21!24).…”

Pd-catalyzed reactions of cyclopropanols, cyclobutanols and cyclobutenols

“…97, 93 Sarpong and co-workers used a variety of vinyl bromides or iodides. 94 Optimization of the reaction conditions led to retain Pd(PCy 3 ) 2 as the catalyst and 1,4-dioxane as the solvent (Eq. 99).…”