Visible light photoredox and Polonovski-Potier cyclizations for the synthesis of (±)-5-epi-cermizine C and (±)-epimyrtine

Abstract

The key step involved an allylsilane cyclization with an iminium ion formed by oxidation of a tertiary amine. Oxidative annulation was promoted either catalytically by visible light photoredox catalysis or by stoichiometric Polonovski-Potier conditions. There was a modest difference in diastereoselectivity between the two methods, with photoredox providing the key quinolizidine intermediate in 4.7:1 dr versus 2:1 dr for the Polonovski route.

Photoredox-Catalyzed C–H Functionalization Reactions

“…In a related synthesis, Marvin and co-workers utilized a photoredox-mediated cyclization as a key step in the synthesis of (±)-5- epi -cermizine C ( 92.3 ) and (±)-epimyrtine ( 92.4 ) (Scheme ). The iminium ion undergoes cyclization in the presence of a tethered allylsilane, affording the fused ring product in 50% yield and 4.7:1 dr. This intermediate was subjected to two subsequent parallel transformations to furnish the two desired natural products.…”

Strategic Use of Visible-Light Photoredox Catalysis in Natural Product Synthesis

“…124 This method of generating an iminium cation was utilized by Marvin and co-workers in total syntheses of the quinolizidine alkaloids (±)-epimyrtine and (±)-5-epi-cermizine (235) (Scheme 44). 125 A prerequisite for a successful aza-Prins cyclization is the ability to cogenerate the iminium cation and the trapping nucleophile. The stability of the highly reactive allylsilane nucleophile to the Ru(bpy) 3 Cl 2 -catalyzed generation of iminium ion intermediate 236 is a notable feature of this total synthesis.…”

A Practical Total Synthesis of (±)-Cermizine D and a Formal Synthesis of (±)-Cermizine C

“…1). [5][6][7][8][9][10][11][12] Although cermizine C has been the topic of numerous synthetic papers, 7,8,[13][14][15][16][17][18][19][20][21][22] to date there have been only three total syntheses of cermizine D. 20,[23][24][25] In 2008, Takayama and co-workers reported the first asymmetric total synthesis of (+)cermizine D, which consisted of an 18-step route featuring an oxazolidinone intermediate as a key cyclisation precursor. 20,23 In 2012, a second synthesis of (+)-cermizine D was published by Carter and collaborators, which included two different approaches, a nine-step cuprate addition strategy and a PhSCH 2 I alkylation pathway in 16 steps overall.…”