First total synthesis of (+)-indicanone

Abstract

The first total synthesis of the guaiane-type sesquiterpene, (+)-indicanone (1), isolated from the root of Wikstroemia indica, was accomplished based on the rhodium(I)-catalyzed Pauson-Khand-type reaction of the allenyne derivative, which was derived from (+)-limonene. This total synthesis unambiguously confirmed the complete structure of (+)-indicanone involving its absolute stereochemistry.

Application of Pauson–Khand reaction in the total synthesis of terpenes

“…In addition, this total synthesis conrmed the complete structure and absolute stereochemistry of (+)-indicanone 454, unambiguously (Scheme 35). 288 In 2000, Fukuyama and his research group isolated merrilactone A 469, a complex cage-shaped pentacyclic sesquiterpene, from extract of Illicium merrillianum. 289 Its structure was fully characterized showing it has an oxetane moiety, two glactone functionalities, and a highly substituted cyclopentane ring at its core.…”

“…Wikstroemia indica has been used to treat pneumonia, rheumatism, and bronchitis as folk medicine in China for long time. In 2012, the total synthesis of (+)-indicanone 454 was reported by Mukai and co-workers 286 through the Rh( i )-catalyzed Pauson–Khand reaction of the allenyne derivative which was derived from (+)-limonene.…”

Natural sesquiterpenoids

“…407 The rst total synthesis of (+)-indicanone has been reported. 408 New guaianolides have been isolated during the period covered by this review (see Table 3). The novel guaian-6a,12olides, i.e.…”

Conditions for a Rh(I)-catalyzed [2+2+1] cycloaddition reaction with methyl substituted allenes and alkynes

“…16 Reaction of 8a with Mukai's conditions of 10 mol% rhodium (1,5-cyclooctadiene) chloride dimer ([Rh(cod)Cl] 2 ) and 50 mol% 1,3-bis(diphenylphosphino)propane (dppp), to produce the Rh (I) monomer [Rh(CO)(dppp) 2 ]Cl, afforded dienone 10a in 27% yield (entry 9, Table 1). Lowering the concentration of this reaction to 0.01 M gave a 46% yield of dienone 10a (entry 10).…”

“…Lowering the concentration of this reaction to 0.01 M gave a 46% yield of dienone 10a (entry 10). Finally, [Rh(CO)Cl(dppp)] 2 , a dimeric Rh(I) catalyst produced from 10 mol% [Rh(cod)Cl] 2 and 20 mol% dppp, also used by Mukai for methyl substituted allenes and alkynes, 16 was used for the cyclocarbonylation of allene-yne 8a at 0.01 M, but this reaction only produced 1 0a in 29% yield (entry 11). The operational simplicity of the cyclocarbonylation reaction with rhodium biscarbonyl chloride dimer versus either of Mukai's catalyst systems led us to focus our efforts on the former.…”