Divergent Synthetic Route to Oxidized Benzofulvene Sesquiterpenoids: Protecting‐Group‐Free Total Synthesis of Nicotianasesterpenes A, B, and a Polygonum Sesquiterpenoid

Abstract

A divergent approach toward the protecting‐group‐free total synthesis of oxidized benzofulvene sesquiterpenoids is described. Highlight of our synthesis includes regio‐ and stereoselective assembly of the common intermediate 9 by the orchestrated application of a Pd(0)‐catalyzed reductive dehalogenation, a solvent‐free methylenation, and a vinylogous Stork enamine aldol condensation in a substrate‐controlled manner. The advanced intermediate 9 was efficiently transformed to nicotianasesterpenes A, B, and a polygonum sesquiterpenoid, respectively.

“K‐synthesis”: Recent advancements in natural product synthesis enabled by unique methods and strategies development in Korea

“…33 Sung-Gon Kim (single-handedly!) reacted aldehyde 101 and nitrosobenzene (102) in the presence of L-proline (103) to produce aldehyde intermediate 104 (Scheme 7a). This aldehyde intermediate 104 was subsequently allowed to react with allyl bromide, In, and sodium iodide to yield alcohol 105 as a 4:1 diastereomeric mixture.…”

“…Notably, Yun and coworkers utilized the vinylogous Stork enamine aldol condensation strategy for the synthesis of various anmindenol A derivatives as well as nicotianasesterpenes A and B. 103…”

“…The bromide moiety of the resulting alcohol product was methylated by a Negishi cross‐coupling reaction to yield the first synthetic sample of anmindenol A ( 315 ). Notably, Yun and coworkers utilized the vinylogous Stork enamine aldol condensation strategy for the synthesis of various anmindenol A derivatives as well as nicotianasesterpenes A and B 103 …”

Evolution of Strategies in Protecting‐Group‐Free Synthesis of Natural Products: A Recent Update

“…[ 126 ] These benzofulvenes have different types of biological activities such as anti‐inflammatory, anti‐proliferative and anti‐viral properties and can be used as pharmaceutical leads. [ 126 ] Yun and co‐workers [ 127 ] synthesized nicotianasesterpenes A and B as shown in Scheme 43. The indanone 358 on dibromination followed by methylation yielded 359 , which on mono dehalogenation using triethylsilane and Pd(OAc) 2 as a catalyst gave 360 .…”

Rapid Access to cis-1,3-Dialkylindanes: Asymmetric Formal Syntheses of epi-Mutisianthol and epi-Jungianol

“…9b The synthesis of indane 4 commenced from the known indanone 12, which was previously reported by our group (Scheme 3). 12 The exposure of 12 to TMSOTf and Et3N, oxidation of the resulting silyl enol ether with IBX•MPO complex provided indenone 15 in good yield for 2 steps. 10 Careful Grignard reaction of 15 with MeMgI under the low temperature effectively gave precursor 10 in 58% yield.…”