Asymmetric Total Synthesis of (−)‐Dehydrocostus Lactone by Domino Metathesis

Abstract

Dedicated to Professor Barry Trost on the occasion of his 80th birthdayAn efficient total synthesis of the sesquiterpenoid (À )-dehydrocostus lactone is reported. Our earlier approach by a domino enediyne metathesis was extended by a domino dienyne metathesis strategy to give access to suitably functionalized hydroazulene cores. Highly stereoselective asymmetric anti aldol reactions provided the enantiopure substrates for this key step of our synthesis. Multiple hydroboration/oxidation of the resulting hydroazulenes set up three out of four stereogenic centers in a single step. First, oxidation to give a diketo-γlactone enabled an enantioselective formal synthesis of the target guaianolide. Subsequently, the final steps of this approach were improved by using a double carbonyl olefination at the stage of a masked γ-butyrolactone, which completed the synthesis in a much more efficient way.

Prins cyclization of 1,3-dioxinone: synthesis of 11-epi-badkhysin

“…1,9 There is a crucial issue in the synthesis of 6,12-guaianolide type STLs, namely the construction of the central highly functional seven-membered ring. Representative methodologies for these medium-sized carbocyclic rings are ene-cyclization, 10 the intramolecular Nozaki–Hiyama–Kishi type coupling reaction, 11 the metathesis approach, 10 a ,12–15 oxidative ring-opening, 16 photosantonin-type ring rearrangement, 17 pinacol coupling, 18 radical cyclization, 19 and tungsten-catalyzed cyclization. 20…”

Climbing the Oxidase Phase Ladder by Using Dioxygen as the Sole Oxidant: The Case Study of Costunolide

“…With ample quantities of santamarine ( 12 ) and reynosin ( 11 ) at our disposal, we considered a cyclase phase to gain access to the biologically intriguing 6,12- Asteraceae lactone guaiane cores (Scheme ; black box). Hence, activation of the secondary alcohol at the C1 position of both reynosin and santamarine by mesylation to obtain derivatives 18 and 19 [MsCl (3 equiv), Et 3 N (6 equiv), THF], followed by solvolytic rearrangement with potassium acetate in acetic acid, resulted in the synthesis of dehydrocostus lactone ( 20 ) (55% yield from reynosin) and isodehydrococtus lactone ( 22 ) (70% yield from santamarine) as the major products, along with the isomerized alkene product 21 in less than 10% yield for the reaction of reynosin (Scheme ; black box) …”