Meroterpenoid total synthesis: Conversion of geraniol and farnesol into amorphastilbol, grifolin and grifolic acid by dioxinone- β -keto-acylation, palladium catalyzed decarboxylative allylic rearrangement and aromatization

Abstract

Biomimetic total syntheses of resorcinols amorphastilbol, grifolin and grifolic acid have been completed in four steps starting from geraniol and farnesol without the use of phenolic protection. The key steps involve C-acylation of dioxinone-β-keto esters, followed by palladium catalyzed decarboxylative allylic rearrangement and biomimetic aromatization.

Meroterpenoid Synthesis via Sequential Polyketide Aromatization and Cationic Polyene Cyclization: Total Syntheses of (+)-Hongoquercin A and B and Related Meroterpenoids

“…Dioxinone β,δ-diketo ester 15 , in turn, should be available via C -acylation of dioxinone β-keto ester 16 , which, in turn, is available from trapping a dioxinone acylketene with trans , trans -farnesol ( 17 ). 10…”

“…Following our recently published methods, 10 thermolysis of dioxane-4,6-dione keto dioxanone 19 at 55 °C generated the dioxinone acyl ketene 11 , which was trapped with trans , trans -farnesol ( 17 ) to provide dioxinone β-keto ester 21 (79%) (Scheme 4). Magnesium chloride mediated regioselective C -acylation of β-keto ester 21 with acetyl chloride gave dioxinone β,δ-diketo ester 23 , which on reaction with Pd 2 (dba) 3 and tri(2-furyl)phosphine resulted in a highly regioselective decarboxylative allylic rearrangement giving the β,δ-diketo dioxinone 9 and readily aromatized in situ to produce farnesyl resorcylate 14 (55% overall from 21 ).…”

“…9 More recently, we developed an efficient methodology for the synthesis of dioxinone β-keto esters 12 using dioxane-4,6-dione keto dioxanones 10 as the masked dioxinone acylketene 11 (Scheme 2). 10 Application of this reaction provided an efficient route for the synthesis of β-resorylates, and its utility has been showcased in the total syntheses of several bioactive meroterpenoid natural products. 10 Herein we report further extensive studies on the dual biomimetic total synthesis of the hongoquercins 5 , which we initially published as a communication.…”

“…10 Application of this reaction provided an efficient route for the synthesis of β-resorylates, and its utility has been showcased in the total syntheses of several bioactive meroterpenoid natural products. 10 Herein we report further extensive studies on the dual biomimetic total synthesis of the hongoquercins 5 , which we initially published as a communication. 9e…”

Biomimetic Syntheses of Amorfrutin C and C‐5 Substituted Amorfrutin Analogues

“…The retrosynthetic disassembly of resorcylate 5 involves the biomimetic aromatization of β,δ‐ diketo dioxinone 20 , which would, in turn, be prepared through a regioselective C ‐acylation of dioxinone β ‐ketoester 18 , followed by palladium(0)‐catalyzed decarboxylative prenyl rearrangement (Scheme 1C) [12,13a] . Our regioselective acyl‐ketene generation would be key for the preparation of 18 from dioxinone acid 17 , derived from dioxinone 16 [13a,b] …”