Photoinduced Skeletal Rearrangements Reveal Radical-Mediated Synthesis of Terpenoids

Abstract

Protecting-group-free synthesis of (+)-ent-kauradienone and (À)-jungermannenone C has been accomplished through sequential applications of three radical-based reactions, including late-stage photoinduced skeletal rearrangements of bicyclo[3.2.1]octene ring systems. Further investigations on various terpenoids showed good functional-group tolerance and suggest that some terpenoids could also be produced via such photoinduced rearrangements pathways in nature. Our work demonstrates how paying more attention to unconventional radical mechanisms can reveal new chemistries that facilitate the synthesis of complex natural products.

Enantioselective Total Synthesis of (+)‐Jungermatrobrunin A

“…Our hypothesis was confirmed by the fact that upon UV irradiation of (+)‐ 4 at 254 nm, 75 % of (−)‐ 2 was isolated (Table , entry 5). Although we had already described this rearrangement of ent ‐kaurene into jungermannenone skeletons via a photo‐induced 1,3‐acyl migration of the β,γ‐unsaturated ketone in a previous publication, we did not envision that this transformation could also smoothly proceed with a much more complex and oxygenated substrate. Clearly our current observation further demonstrates the potential of this photo‐induced radical reaction in complex molecule synthesis.…”

“…However,u pon UV irradiation of (À)-2 at 365 nm in MeOH, (+ +)-4 was isolated in 14 %yield along with 81 %recovered (À)-2 ( Table 1, entry 4). Although we had already described this rearrangement of ent-kaurene into jungermannenone skeletons via aphoto-induced 1,3-acyl migration of the b,g-unsaturated ketone in ap revious publication, [17] we did not envision that this transformation could also smoothly proceed with am uch more complex and oxygenated substrate.C learly our current observation further demonstrates the potential of this photo-induced radical reaction in complex molecule synthesis. [16] Our hypothesis was confirmed by the fact that upon UV irradiation of (+ +)-4 at 254 nm, 75 %o f( À)-2 was isolated ( Table 1, entry 5).…”

“…[17] We expect that the photo-induced 1,3-acyl migration will find more applications in natural product synthesis. Our work indicates that the photochemical reactions may also occur in the biosynthesis of ent-kaurene diterpenoids.…”

Enantioselective Total Synthesis of (+)‐Jungermatrobrunin A

“…[16] Our hypothesis was confirmed by the fact that upon UV irradiation of (+ +)-4 at 254 nm, 75 %o f( À)-2 was isolated (Table 1, entry 5). Although we had already described this rearrangement of ent-kaurene into jungermannenone skeletons via aphoto-induced 1,3-acyl migration of the b,g-unsaturated ketone in ap revious publication, [17] we did not envision that this transformation could also smoothly proceed with am uch more complex and oxygenated substrate.C learly our current observation further demonstrates the potential of this photo-induced radical reaction in complex molecule synthesis.…”

“…Our work indicates that the photochemical reactions may also occur in the biosynthesis of ent-kaurene diterpenoids. [17] We expect that the photo-induced 1,3-acyl migration will find more applications in natural product synthesis.…”