Acorenone synthesis

This same concept applies to spiroannulations of six membered rings and is illustrated in a synthesis of acorenone B 155 as outlined in Scheme 547). The notion of alkylative carbonyl transposition permits the spiro enone 156 to become a logical intermediate. The standard analysis by a retro-aldol process translates the spiro ring system of acorenone B into a geminal alkylation problem as revealed by... 

The possibility of readily introducing a meta sidechain to an anisole has enabled design an unusual synthesis of acorenone [17]. 

Copper catalysed decomposition of diazoketone 41 furnishes tricyclic ketone 42 in 83% yield (equation 52) which provides the key building block in the synthesis of chysomelidi-al81. A few similar instances of cyclopropanation are to be found in the syntheses of ( )-hinesol 4382, (-)-acorenone B 44, ( )-spirolaurenone 45s4 and (t)-descarboxyquadrone 4685 (equations 53-56). 

These epoxides can be converted to vinyl siloxycyclopropanes m high yield by treatment with base and trimethylsilyl chloride. Transformations of these interesting intermediates (see Section VII) into various products are demonstrated in equation 103. Isolation of oxaspiropentanes is not required in a route to cyclobutanones which are formed by straightforward acid workup (equation 104) . These can either be expanded to y-butyrolactones by oxidation or to an enol ester by a-formylation and acid-induced fragmentation. The latter sequence has been utilized in a synthesis of acorenone... 

Previously it had been shown that low temperature irradiation of the enone (168) gave the tricyclic ketone (169) as the major product. It has now been reported99 that further photolysis of (169) at 0—5 °C promotes a Norrish type II process to give the ketone (170) which can be converted into a-acoradiene (171). Epimerization of the isopropenyl group in (170) can be achieved by silver nitrate, thus paving the way for a synthesis of acorenone B (172). Pertinent to these results is the finding... 

Several new synthetic routes to acorane sesquiterpenoids have been published during the past year cf. Vol. 8, p. 76). In the first of these routes spiroannulation of the pyrrolidine enamine (201) derived from cyclopentene aldehyde (200) provided an enone (202) which was subsequently converted into (-)-acorenone (203) (Scheme 19). In an alternative synthetic route,Robinson annulation of the aldehyde (204) with methyl vinyl ketone provided a spiro-ketone (205) which served as a common intermediate in the synthesis of (-)-acorenone (203) and (-)-acorenone-B (211) (Scheme 20) cf. Vol. 7 pp. 63, 64). To explain the conversion of (206) into (209), it has been suggested that the intermediate 1,2-borane borate (207) undergoes elimination followed by hydroboration. 

The products are the fused bi-cyclic ring system as a mixture of diene isomers, and the spirocychc system [29]. The product ratio is dependent on the length of the chain and on the reaction conditions. Kinetic conditions in the example shown favor the fused bi-cyclic product, whereas thermodynamic conditions deliver the spirocyclic system. This approach was subsequently applied in a rapid synthesis of acorenone and acorenone B (see Chap. 8) [30]. 

One of the first eye-catching synthetic applications of arene-chromium chemistry was the synthesis of the sp/ro-sesquiterpenes ( )-acorenone and ( )-acorenone B (rac-7) disclosed by Semmelhack and Yamashita in 1980 [14]. These authors twice exploited the meta-selective nucleophile addition to anisole-Cr(CO)3 derivatives (Scheme 1). Starting from complex rac-1, such a reaction is first used for the regioselective introduction of an acyl sidechain to give 2 after oxidative workup. A few steps later, the nitrile rac-4 (obtained from rac-3 by complexation and separation of the diastereomeric products by preparative HPLC) is deprotonated to form the spiro addition product rac-5, from which the enone rac-6 is obtained after protonation and hydrolysis of the initially formed dienol ether. The final conversion of rac-6 into acorenone B (rac-7) efficiently proceeds over five steps and involves a diastereoselective hydrogenation of an exo-methylene group. 

Scheme 1 Total synthesis of ( )-acorenone B (rac-7) according to Semmelhack...

The cleavage with hydrogen chloride was used in a synthesis of (—)-acorenone... 

A new strategy for the synthesis of spiro[4,5]decane sesquiterpenoids has been developed which relies upon the activating and meta-directing effects of the tricarbonylchromium group in 7r-anisoletricarbonylchromium complexes with cyano-stabilized nucleophiles. This new methodology is nicely illustrated in the synthesis of acorenone (175) and acorenone B (176), which combine both inter- and intra-molecular variants of the process (Scheme 21). 

Azo-dienophiles give more ene adduct than the corresponding substituted carbo-dienophile. The spirosesquiterpenoids ( )-jS-acorenol, ( )-/3-acoradiene, ( )-acorenone-B, and ( )-acorenone have all been synthesized from the ester (40). The key step, as previously described for the /8-acorenol synthesis, is the 100% endo-selective intramolecular ene reaction of the 1,6-diene (41) to a mixture of the epimers (42a and b). ... 

An intramolecular cycloaddition of an a diazoketone, a reaction which has featured prominently this year, forms the key step, (250) - (251), in a synthesis of solavetivone. By contrast, intramolecular cycloadditions of car-benoids derived from a-diazoketones have been used in total synthesis of ( )-a-chamigrene and (-)-acorenone B in the latter case, (+)-limonene was used as the chiral precursor. ... 

M.F. Semmelhack, A. Yamashita - Arene-Metal Complexes in Organic Synthesis, Synthesis of Acorenone and Acorenone B, J. Am. Chem. Soc. 102,5924,1980. 

Reactions that generate carbon-carbon bonds via the addition of a carbanion to an arene metal complex or to a hydro-arene complex are likely to join the ranks of those which are sufficiently powerful that a whole synthetic route can be built around their use. Thus Semmelhack and co-workers report a synthesis of acorenone B (84) in which the key step is the conversion of (82) to (83). ... 

In a total synthesis of the natural sesquiterpene ( — )-acorenone B (186), White and his co-workers employed as a key stage the intramolecular cycloaddition of a... 

The rearrangement of adducts of enol acetates derived from a-diketones has been reported. An interesting application of this principle was in a model study for the synthesis of acorenones (Scheme 14) in which the adduct (49) underwent rearrangement in base to (50) which was cleaved with lead tetra-acetate to generate the spirocyclic product (51). ... 

The synthesis of the naturally occurring spirocyclic sesquiterpene (-l-)-acorenone B 28 will exemplify the use of substrate control in the [2,3]-sigmatropic rearrangement of a sulfonium ylide. The p-keto diazo ester 25 was obtained from commercially available (—)-perillaldehyde 24 in... 

Kido F, Abiko T, Kato M. Spiroannulation by the [2,3]-sig-matropic rearrangement via the cyclic aUylsulfonium ylide. A stereoselective synthesis of (+)-acorenone B. J. Chem. Soc., Perkin Trans. 1 1992 (2) 229-233. 

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