Synthesis of (-)-acorone and related spirocyclic sesquiterpenes

Abstract

Total syntheses for four acorane sesquiterpenes, 0-acoradiene (4), -acoradiene (5), and the enantiomers (27 and 28) of acorone (1) and isoacorone (2), are described. The synthetic route involves conversion of (fi)-pulegone (11) into 3-methyl-2-carbethoxycyclopentanone (8) by improvement of literature procedures, then conversion of this into (fi)-3-methyl-2-methylenecyclopentanone (17) by the sequence ketalization, reduction, deketalization, and dehydration, A Diels-Alder reaction between 17 and isoprene gave four adducts 18-21. The para:meta ratio in this reaction was improved from 2:1 to 24:1 by the use of SnCl4 catalysis, which gave a ratio of products of 69: 27:3:1. Structures were assigned to the various isomers on the basis of the known steric and electronic requirements in the Diels-Alder reaction. The major ketones 18 and 19 were purified by preparative high-pressure liquid chromatography. Treatment of 18 with isopropyllithium and then SOCI2 gave -acoradiene (4) and its endocyclic isomer 23, whereas 19 led to -acoradiene (5) and its isomer 25. Hydroboration of 25 followed by Jones oxidation gave an equilibrium mixture of (-)-acorone ( 27), the enantiomer of natural acorone (1), and (+)-isoacorone ( 28), the enantiomer of natural isoacorone (2).Acorone (1), isolated from the oil of Sweet Flag, Acorus calamus L., is the best known member of a small group of spirocyclic sesquiterpenes having the acorane skeleton.3 Other members include isoacorone (2), cryptoacorone (3), and acorenone from the same source,3 as well as acorenone B from Bothriochoa intermedia,4, two unnamed dienes from Vetiveria zizanoides,4 5 and -acorenol, /3-acorenol, aacoradiene, /3-acoradiene, -acoradiene (4), and -acoradiene (5) from Juniperus rígida.5 -Alaskene, isolated from alaska cedar, Chamecyparis nootkatensis, was shown to be identical with -acoradiene, but /3-alaskene from the same source was shown to be enantiomeric to -acoradiene.6 4 5

Revision of the Structure of the Major Aggregation Pheromone of the Broad-horned Flour Beetle (Gnatocerus cornutus) to (1S,4R,5R)-α-Acoradiene by Its Synthesis

“…The starting material was known ketone 3 (a 1:1 mixture of its diastereoisomers), which had previously been synthesized by Marx 3) and also by Weyerstahl,4) starting from (R)-(+)-pulegone (2). Our attempts failed to add one carbon atom at the carbonyl group of 3 by a Wittig reaction with either methoxymethylene triphenylphosphorane or methylene triphenylphosphorane.…”

“…The known (À)-trans-pulegenic acid (10) 12) derived from (S)-(À)-pulegone (2) according to Marx 3) was converted to (À)-cis,trans-puleganolide (11) under acidic conditions. 13) Alkylation of lactone 11 with known iodide 12 14) gave 13, which was subjected to an elimination reaction by treating with potassium tbutoxide in N,N-dimethylformamide (DMF) according to Wolinsky,8) Intramolecular aldol condensation of 18 with sodium hydroxide in aqueous ethanol 15) afforded ,-unsaturated ketone 19 in a high yield of 97%, this being converted to triene 20 by the Wittig reaction.…”

3-Substituted and 2,3-Disubstituted Cyclopentanones via an Asymmetric Tandem 1,4-Addition/Dieckmann Cyclization

“…The enantiomeric excess and the absolute configuration of 8a at C-3 were determined by comparison of its optical rotation with an authentic sample prepared from (R)-pulegone. 18 The absolute configuration of 8b 19 and 8c 20 was determined by comparison of the optical rotation of the prepared 3-substituted-cyclopentanones 9 with the reported value. For the determination of the absolute configuration of 8e we compared the optical rotation of our 2-carbomethoxy-3-vinylcyclopentanone 8e 17 with the reported value of the same compound ([a] D 20 = +85.05) synthesized from Helmchen and co-workers.…”

Synthesis based on cyclohexadienes Part 36: an efficient methodology for the construction of spiro[4.5]decanes: a formal synthesis of acorone

“…However, treatment of the spirohydroxy acid 29a with Ph 3 P/DEAD 19 in anhydrous THF afforded the desired ketones 31a and 32a as a 1:1 epimeric mixture. The structure of the ketones was deduced from their spectra data and finally by comparison 20 with an authentic sample, kindly provided by Professor Marx. The ketone 31a has been converted 20 earlier into acorone and other related compounds, thus completing a formal synthesis of these spiro [4.5]decane sesquiterpenes.…”