An Approach Toward the Bridged 14‐Membered Carbon Macrocycle of Bielschowskysin

Abstract

Relying on our previous achievements toward the a total synthesis of bielschowskysin, [1][2][3][4][5] we herein report additional efforts to close the bridged tetradecane carbocyclic core of this marine diterpene. The key step of this strategy is an

Polycyclic Furanobutenolide-Derived Cembranoid and Norcembranoid Natural Products: Biosynthetic Connections and Synthetic Efforts

“…66,67–69 Access to tricycle 153 in enantioenriched form was envisioned from cyclobutanol (+)-154. Bicycle (+)-154 would be synthesized from racemic ketone (±)-155 by a classical resolution, where cyclobutane (±)-155 is commercially available, being synthesized by the thermal [2 + 2] cycloaddition between cyclopentadiene and dichloroketene.…”

“…67 Toward this end, alkenyl iodide 165 was first advanced through a palladium-catalyzed carbonylation, which proceeded with concomitant lactonization, furnishing butenolide 171 after ketal cleavage in 99% yield over two steps (Scheme 36). After cleavage of the methoxymethyl ether using TMS bromide, triol 172 could be sequentially oxidized using manganese dioxide in ethyl acetate to provide lactone 173 followed by Swern oxidation completed aldehyde 174.…”

“…In the face of the challenges encountered in their efforts toward BSK ( 6 ), Mulzer and co-workers designed a third-generation synthetic strategy toward BSK ( 6 ) hinging on the production of core scaffold 153 from a cyclobutane-containing feedstock (Scheme ). − Access to tricycle 153 in enantioenriched form was envisioned from cyclobutanol (+)- 154 . Bicycle (+)- 154 would be synthesized from racemic ketone (±)- 155 by a classical resolution, where cyclobutane (±)- 155 is commercially available, being synthesized by the thermal [2 + 2] cycloaddition between cyclopentadiene and dichloroketene.…”

“…Presumably without any success in advancing dihydrofuranol 168 through the key macrocyclization step, Mulzer and co-workers recently revealed yet another reevaluation of their synthetic strategy focusing on an alternative macrocyclization strategy . Toward this end, alkenyl iodide 165 was first advanced through a palladium-catalyzed carbonylation, which proceeded with concomitant lactonization, furnishing butenolide 171 after ketal cleavage in 99% yield over two steps (Scheme ).…”

“…Presumably without any success in advancing dihydrofuranol 168 through the key macrocyclization step, Mulzer and coworkers recently revealed yet another reevaluation of their synthetic strategy focusing on an alternative macrocyclization strategy. 67 Toward this end, alkenyl iodide 165 was first advanced through a palladium-catalyzed carbonylation, which proceeded with concomitant lactonization, furnishing butenolide 171 after ketal cleavage in 99% yield over two steps (Scheme 36). After cleavage of the methoxymethyl ether using trimethylsilyl bromide, triol 172 could be sequentially oxidized using manganese dioxide in ethyl acetate to provide lactone 173, which was subjected to Swern oxidation to complete aldehyde 174.…”