Enantiospecific Total Synthesis of (−)-Japonicol C

Abstract

An efficient and convergent first total syntheses of (±)-japonicol B and (−)-japonicol C have been completed. The notable points of the synthetic route are Lewis-acid-catalyzed Friedel–Crafts reaction for one pot C–C and C–O bond formations resulting in construction of the tricyclic meroterpenoid skeleton, one pot Pd­(OH)2/C-catalyzed isomerization/hydrogenation, and site selective sp 3 C–H oxidation.

Construction of Benzo‐Fused Heterocycles by Epoxide–Heteronucleophile Cyclization: Applications in the Synthesis of Natural Products and Designed Molecules

“…Very recently, Dethe and Nirpal has shown that EPC reaction could also be implemented as a part of epoxide-opening cascades towards a double cyclization reaction. [58] In this work, the authors observed that m-CPBA-mediated double epoxidation of compound 187 furnished epoxide 188 as an inseparable diastereomeric mixture in a 1:0.6 (Scheme 44). Next, treatment of epoxide 188 with K 2 CO 3 in MeOH/H 2 O (2 : 1) delivered japonicol B (189) and epi-japonicol B (190) in a 1 : 2 ratio in 84 % yield.…”

Total Synthesis of Natural Terpenoids Enabled by Cobalt Catalysis

“…Dethe ( Dethe and Nirpal, 2021 ) described the enantiospecific total synthesis of japonicol C (41). The allyl alcohol 38 could be advanced to ( R )-(+)-limonene (37) in six steps.…”

Recent advances in the synthesis of natural products containing the phloroglucinol motif

“…141,142 Dethe's total synthesis of japonicol B ( 182 ) was promoted by an epoxide-opening cascade cyclization strategy (Scheme 34). 143 Through Friedel–Crafts alkylation of acylphloroglucinol 34 with geraniol, followed by subsequent acetylation and epoxidation, Dethe prepared an intermediate 181 that allowed access to japonicol B ( 182 ) and its C-3 epimer in 1 : 2 dr after cyclization and deprotection under basic conditions.…”

“…In addition, Dethe and coworkers also accomplished the enantiospecific synthesis of (−)-japonicol C ( 186 , Scheme 35). 143 The benzo[ b ]cyclopenta[ e ]oxepine core ( 185 ) of japonicol C was rapidly assembled using the Friedel–Crafts reaction between 183 and alcohol 184 , followed by MOM deprotection and acetylation. Notably, acylphloroglucinol 183 was protected at the para position to ensure regioselective cyclization.…”