Total Synthesis of (+)-Cyperolone

Abstract

The total synthesis of (+)-cyperolone, an eudesmane-derived sesquiterpenoid from Cyperus rotundus, is described. The de novo synthesis was accomplished via a 15 step sequence starting from (R)-(-)-carvone. The synthetic route features a platinum-catalyzed cycloisomerization to rapidly construct the bicyclic core from a 3-silyloxy-1,5-enyne intermediate.

Sulfonyl Hydrazides in Organic Synthesis: A Review of Recent Studies

“…They were successfully used for the total synthesis of natural products, which included Brasilicardins A and C, (+)‐Frondosin A, (+)‐Tanikolide, Lundurines A−C, Onoseriolid, Isobolivianine, (−)‐Crinipellin A, Panaginsene, Echinopines, (+)‐ and (−)‐Isolaurepan, (−)‐Strychnofoline, (−)‐Clovan‐2,9‐dione, (+)‐Sarcophytin, [2 ° ] (+)‐Chatancin, [2 ° ] (−)‐3‐Oxochatancin, [2 ° ] (+)‐Cyperolone . In these cases, TsNHNH 2 reacted with aldehydes (or ketones) to form hydrazones that underwent cycloaddition or reduction subsequently. Banford‐Stevens reaction and Shapiro reaction were reported in this decade.…”

[1, 2]‐Migration Reactions Catalyzed by Gold Complexes and their Applications in Total Synthesis

“…3) . This cyclization strategy was the key step of the total synthesis of (+)‐cyperolone, although in this particular case platinum(IV)chloride was superior to gold catalysts . Kirsch, Rhee and co‐workers also studied the analogous reactivity 3‐silyloxy‐1,6‐enynes in the presence of gold catalysts .…”

“…[19] This cyclization strategy was the key step of the total synthesis of (+)-cyperolone, although in this particular case platinum(IV)chloride was superior to gold catalysts. [20] Kirsch, Rhee and co-workers also studied the analogous reactivity 3-silyloxy-1,6-enynes in the presence of gold catalysts. [21] The 1,6-enynes may react through two different pathways: i) 6-exo carbocyclization followed by pinacol rearrangement or ii) heterocyclization followed by Claisen rearrangement.…”

3.16 The Semipinacol Rearrangements

“…55 Using this method as the key step, Kirsch and coworkers finished the total synthesis of (þ)-cyperolone (Scheme 45). 56 For 3-silyloxy-1,6-enyne compound, the corresponding tandem process will start with a 6-exo-dig cyclization of the alkene moiety with gold(I) catalyst. 57 It has been found that the electronic property of the phosphine ligand affects the selectivity of this transformation significantly.…”