Scalable Enantioselective Total Synthesis of (−)‐Goniomitine

Abstract

A scalable enantioselective total synthesis of (−)‐goniomitine has been developed by using an iridium‐catalyzed asymmetric hydrogenation of an exocyclic enone ester to control the configuration of the molecule. The synthesis begins from commercially available starting materials, and proceeds through an integrated asymmetric ketone hydrogenation, Johnson–Claisen rearrangement, and one‐pot oxidation/deprotection/cyclization process. With this highly efficient and scalable strategy, (−)‐goniomitine was synthesized in eleven steps with 27 % overall yield, and formal enantioselective syntheses of (+)‐1,2‐dehydroaspidospermidine, (+)‐aspidospermidine, and (+)‐vincadifformine were also achieved.

Bifunctional Homogeneous Catalysts Based on Ruthenium, Rhodium and Iridium in Asymmetric Hydrogenation

“…AH of ketones, lactones and -ketoesters using an iridium catalyst based on a P(NH)N spiro ligand by Zhou, Xie and co-workers. [219][220][221][222][223][224][225][226][227][228][229][230][231][232][233][234] This method provides one of the most impressive recent applications of Ir-bifunctional catalysts in asymmetric hydrogenation, in terms of both catalytic efficiency, enantioselectivity, substrate scope and synthetic potential. It is worth to note that Zhang, Yin and co-workers reported in parallel the synthesis of rather similar oxaspirocyclic chiral ligands and applied them to iridium-catalyzed direct asymmetric hydrogenation of Bringmann's lactones (Scheme 73a).…”

“…[220][221][222][223][224] Moreover, this type of iridium(III) catalyst was involved in several DKR processes and enabled the asymmetric total synthesis of compounds of biological interest like crinine-type alkaloids (Scheme 72c), gracilamine alkaloïds, (-)goniomitine, mulinane diterpenoids, (-)-hamigeran B, (-)-mesembrine and others. [225][226][227][228][229][230][231][232] A recent application to the AH/Dynamic kinetic resolution of racemic α-arylamino-γ-lactones and α-arylamino-δlactones led to the corresponding chiral 2-amino diols with high yields and enantioselectivities (Scheme 72d). [233][234] According to theoretical studies, the hydride and proton transfer step proceeds via a cyclic 6membered transition state.…”