A General Entry to Antifeedant Sesterterpenoids: Total Synthesis of (+)‐Norleucosceptroid A, (−)‐Norleucosceptroid B, and (−)‐Leucosceptroid K

Abstract

The first asymmetric total synthesis of the antifeedant terpenoids (+)‐norleucosceptroid A, (−)‐norleucosceptroid B, and (−)‐leucosceptroid K has been accomplished. This highly concise synthetic route was guided by our efforts to develop a platform for the collective synthesis of a whole family of antifeedant natural products. The synthesis features a Hauser–Kraus‐type annulation followed by an unprecedented, highly efficient intramolecular dilactol aldol‐type condensation reaction to produce the 5,6,5 skeleton. The developed synthetic route proceeds for norleucosceptroid A and B in 16 steps (longest linear sequence) from known compounds.

Total Synthesis of Rubriflordilactone B

“…Exposure of 27 to TBAF led to global desilylation and lactonization, providing apair of chromatographically separable epimers,compounds 28 and 29.U ndesired 29 was efficiently converted into 28 upon treatment with LiTMP followed by aqueous workup. [9a] DIBAL-H reduction of 28 furnished lactol 12,which reacted with phosphonate [18] 13 under Masamune-Roush conditions (DBU,L iCl) to give ap air of C23 epimers, 7 and 30,i n moderate yields,p resumably through ao ne-pot HWE olefination/oxa-Michael addition process. [13] Thef acial selectivity of the conjugate addition was excellent, whereas the proto-nation at C23 was poorly controlled.…”

“…at C10 (inconsequential)];b ase treatment ensured full conversion of overreacted cyanohydrins back into the desired ketone.C ompound 19 was subjected to Mukaiyama hydration conditions [Co(acac) 2 ,P hSiH 3 ,O 2 , 10 8 8C] to afford at ertiary alcohol, [15] which underwent lactonization upon exposure to aqueous NaOH at 80 8 8Ct o give compound 20 [ca. [9a] DIBAL-H reduction of 28 furnished lactol 12,which reacted with phosphonate [18] 13 under Masamune-Roush conditions (DBU,L iCl) to give ap air of C23 epimers, 7 and 30,i n moderate yields,p resumably through ao ne-pot HWE olefination/oxa-Michael addition process. at C10 (inconsequential)] with good efficiency.Alow concentration of 19 was crucial to the success of the Mukaiyama hydration, as it suppressed undesired bimolecular radical addition pathways.N otably, treatment of 19 with strong aqueous acid directly delivered 20,p resumably through olefin hydration-cyclization as well.…”

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

“…381 Isolated in 2010, leucosceptroids are relative terpene newcomers, yet several groups have already reported creative solutions to their synthetic construction. In 2013, Liu reported a synthesis of leucosceptroid B ( 308 ), 382 from 2014–2015 the group of Magauer reported the synthesis of eighteen leucosceptroids (including 307 and 308 ), 383,384 and in 2015, Ma reported a chiral pool approach to both 307 and 308 which will be discussed herein. 385 …”

Palladium‐Catalyzed Triple Cyclization of 2,7‐Alkadiynylic Carbonates with Allenes Bearing a Carbon Nucleophile

“…Also, the reactiono fs econdary 2,7-alkadiynylic carbonates (1f, 1g)w ith 4b afforded the tricycles 5fb and 5gb in 60 and 46 %y ields, respectively (entries 8 and 9). The carbon-carbon triple bond at the 8-position of the 2,7-alkadiynylic carbonates 1 may be substituted with an aryl group bearing either electron-deficiento r -rich groups (entries [10][11][12][13][14]. In addition, this methodc ould be extended to 2-thienyl-or cyclohexenyl-substituted 2,7-alkadiynylicc arbonates (entries 15 and1 6).…”

“…[9] No racemization occurred to the central chirality in the starting materials. Due to the importanceo ft his attractive tricyclics keleton, [10] the reactionw ill be potentially useful in organic synthesis and medical chemistry.F urther studies on expanding the scope of the reactiona nd synthetic applications are being pursued in our laboratory.…”