Total Synthesis and Stereochemical Assignment of Actinoranone

Abstract

The total synthesis of four actinoranone stereoisomers led to unambiguous assignment of relative and absolute stereochemistry of the natural product. Key features of the convergent, fully stereocontrolled route include the use of a Negishi carbozirconation/iodination, a Friedel-Crafts cyclization, a Felkin-controlled addition reaction, a Mitsunobu reaction, and a late-stage C-H oxidation.

Formal Synthesis of Actinoranone Using a Racemization-Free One-Pot Semipinacol Rearrangement/Wittig Reaction

“…Precise temperature control and slow addition of the reactants were crucial to avoid premature proto-demetallation, as reported by Ye and co-workers. 15 In summary, intermediate 2 was obtained from (+)-sclareolide in five steps and 47% overall yield ( Figure 2). While our approach shares some of the synthetic transformations used by Ye (15 steps) and Pastre (9 steps), we have been able to shorten the previous sequences to just 5 steps and raise the overall yield fragment 2 to 47%.…”

“…Finally, the coupling of fragments 2 and 3 was carried out following Ye's 15 and Pastre's 16 procedure. The aldehyde fragment was prepared by Dess-Martin oxidation of 15 to give 3, which was directly added to a solution of in situ lithiated vinyl iodide 2.…”

“…Completion of the formal synthesis of actinoranone 1. 15 According to Xu's and Ye's work, 15 actinoranone 1 can be obtained from 16 in three additional steps inverting the configuration at C-15 under Mitsunobu conditions followed by benzylic C-H oxidation using DDQ, and basic hydrolysis of the Mitsunobu ester.…”

“…: +49-30-838-60182; fax: +49-30-838-460182; e-mail: mathias.christmann@fu-berlin.de of several synthesis programs. 13 The first total synthesis of actinoranone was achieved by Ye 15 in 2017 and led to a revision of the initially proposed configuration of 1 (Figure 1). Later that year a formal synthesis was realized by the group of Pastre.…”

Formal Synthesis of Actinoranone Using a Racemization-Free One-Pot Semipinacol Rearrangement/Wittig Reaction

“…Finally, the coupling of fragments 2 and 3 was carried out following Ye's 15 and Pastre's 16 procedure. The aldehyde fragment was prepared by Dess-Martin oxidation of 15 to give 3, which was directly added to a solution of in situ lithiated vinyl iodide 2.…”