Spirovetivane

An alternative approach to the spirovetivanes with electrophilic conjunctive cyclopropyl reagents is illustrated in a synthesis of a-vetispirene, 201 (Scheme 11) 139>. 

The spiro compound 347 constitutes the basic carbon framework found in sesquiterpenes of the spirovetivane and acorane class 184), which have been the target of many syntheses 185). The thermal C3 -> C5 ring expansion 111 -> 347 was of... 

However, an efficient synthesis of the spirovetivane-sesquiterpene a-Vetispirene 392 was achieved initiating the cleavage of the silicon-cyclopropane carbon bond of 160 by fluoride ion. This was effected with anhydrous tetra-n-butyl ammonium fluoride in THF solution containing acetone at reflux temperature for 10 hr. The pentadienyl anion 387 thus generated experienced highly regioselective addition of acetone at the... 

The stereoselectivity of the attack of the enolate on the activated cyclopropane most likely is due to steric factors arising from the preferred pseudoaxial conformation of the incipient methyl group . In other words, the approach of the rather bulky phosphonium salt II is less perturbed by the methyl group when it rests on the opposite side of the molecule in the transition state, presumably in the pseudoaxial conformation, as portrayed in IX. This remarkable stereoselectivity has been put to good use in the synthesis of some natural products of the spirovetivane family. ... 

The reaction between the sodium salt of an a-formylcycloalkanone and the phosphonium cyclopropane has been found to produce spiro compound 605, together with minor amounts of the dihydrofuran 606 (equation 215). This reaction sequence has been used in the synthesis of spirovetivane sesquiterpenes. ... 

The ylid 371 prepared by treating cyclopropyltriphenylphosphonium bromide (with lithium diisopropylamide (LDA) produces a useful synthon on reaction with ethyl chloroformate . The fluoroborate salt (372) was shown to be an excellent reagent for cycloalkenylation of carbonyl compounds. The ylid was used successfully in the total synthesis of Spirovetivanes. ... 

This methodology has been applied to the synthesis of some spirovetivane-type sesquiterpenoids and of ( ) zizaene. ... 

However, a dispatch route to the [4.5]spirocyclic sesquiterpenes of the spirovetivane type has been recently reported from the readily available a-siloxycyclopropane-carboxaldehyde, via the stereospecific thermal ring enlargement of a silylated 1-vinylcyclopropanol (202) (equation... 

The resulting spiro[4.5]decen-2-one (203) is not only a constituent of Vetiver oil of economical importance but also constitutes the key intermediate for the synthesis of other spirovetivane-sesquiterpenes ... 

The acid fragmentation of suitably substituted bicyclo[2.2.2]octanes to cyclohexenones and subsequent ring closure to spirovetivanes via ir-cation cyclization has been used by Murai for a highly stereoselective isolubimin (56) synthesis. (56) has been considered to play an important role in the bio-genetic pathway of various spirovetivane phytoalexins in the Solanaceae family. Treatment of methyl... 

Spiroketones have also been prepared from this aldehyde, such as spirovetivane, a constituent of Vetiver oil used in the perfume industry, and key intermediate for the synthesis of biogenetically related compounds such as a-vestipirene, -vetivone, hinesol, agarospirol. 

Intramolecular Additions to Cyclopentenones - Irradiation (k > 350 nm in THF) of the enone (46) affords a single diastereoisomer identified as (47, 95%). The outcome of the reaction does not seem to be solvent dependent and the same degree of success is obtained with methylene chloride, acetonitrile or methanol as solvents. The corresponding amide also cyclizes efficiently. Crimmins and coworkers have demonstrated that irradiation (X > 350 nm) of the enone (48) results in cycloaddition and the formation of the diastereoisomeric adducts (49) and (50) in a ratio of 83 17. A single product (51) is obtained on irradiation of the related enone (52). These adducts are key intermediates in a synthesis of some spirovetivanes. 

Vetispiranes (spirovetivanes). A group of sesquiterpenes with the skeleton (1). Important sources include vetiver oil [e.g., /S- vetivone and a-vetispirene (2)], a valuable fragrance substance for the perfume industry, and potatoes (Solanum tuberosum) [e.g., sola-vetivone (3), isolubimin (4), lubimin (5), and hydroxy lubimin (6)]. 

A recently published synthesis of /3-vetivone (245) makes use of the hitherto rarely observed y-alkylation of a y-extended enolate anion [e.g. (244) — (245)]. As might be expected, deprotonation of (244) normally leads to the alternative a-alkylation product (246). However, by careful choice of experimental conditions which might be expected to bring about rapid equilibration of all possible enolate anions, the Curtin-Hammett principle is made to apply, and (245) is formed in high yield. Another route to the spirovetivane sesquiterpenes makes use of an acyloin condensation to construct the five-membered ring. ... 

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