Asymmetric Total Synthesis of Rumphellclovane E

Abstract

The first asymmetric total synthesis of rumphellclovane E, a clovane-type sesquiterpenoid, has been accomplished in eight steps from commercially available (R)-carvone. Key elements of the synthesis include Rh-catalyzed cyclopropanation, ironcatalyzed intramolecular reductive aldol reaction, and SmI 2mediated chemo-and diastereoselective reduction of the cyclopentanone.

Samarium(ii) iodide-mediated reactions applied to natural product total synthesis

“…In 2021, Liu and coworkers 56 reported the first asymmetric total synthesis of rumphellclovane E 82, in eight steps from commercially available ( R )-carvone 78 via a B–AB–ABC sequence. Key steps included a SmI 2 -mediated chemo- and diastereoselective reduction of the cyclopentanone to install the desired stereocenter at C2, an iron-catalyzed intramolecular reductive aldol reaction to construct ring C, and a Rh-catalyzed cyclopropanation to construct ring A.…”

Total Synthesis of Clovan-2,9-dione via [3 + 2 + 1] Cycloaddition and Hydroformylation/Aldol Reaction

“…3 Recently, Liu's group reported another strategy (B-AB-ABC) in the asymmetric synthesis of rumphelllcolvane E, using reductive aldol condensation as the key reaction. 5 For the total synthesis of clovan-2,9-dione, two different strategies have been reported. The first asymmetric total synthesis from our group 6 was achieved by using the Rh-catalyzed [3 + 2 + 1] reaction 7 to build the AB ring, followed by aldol reaction to finish the ABC skeleton.…”

“…The reported strategies to construct the skeletons of clovane-type natural products can be divided into several catalogs according to the sequence of building the three rings in the molecules, as shown in Scheme . , As early as the last century, three different strategies, including A-AB-ABC, B-BC-ABC, C-BC-ABC, have been used to synthesize clovene, with Dieckmann condensation or aldol condensation as the key reactions . Recently, Liu’s group reported another strategy (B-AB-ABC) in the asymmetric synthesis of rumphelllcolvane E, using reductive aldol condensation as the key reaction . For the total synthesis of clovan-2,9-dione, two different strategies have been reported.…”

Enantiocontrolled Access to an Intermediate for Highly Functionalized Clovane-Type Terpenoids: Formal Synthesis of Rumphellclovane E

“…During our study, Fu, Liu, and co-workers reported the first asymmetric total synthesis of rumphellclovane E (6) (Scheme 2a). 8 This route is very concise and straightforward for the synthesis of rumphellclovane E (6). However, this route is difficult to apply to the synthesis of other highly functionalized clovane-type terpenoids, such as sarinfacetamides and their derivatives, because of a cyclopropanation/C−C bond cleavage strategy to form a dimethylcyclopentane moiety.…”