A Pipitzol

FIGURE 1.10 The nucleoside analog AZT (27), the specific branched-chain compounds 29 and 30, and the sesquiterpene (-)-a-pipitzol (33, made from 31 and 32) available from sugar starting materials. 

On thermolysis, perezone (192) undergoes a [4+2] cycloaddition to produce equal amounts of the two pipitzols (193) and (194) i.e. there is no stereochemical induction by the chiral centre in (192). If, however, the reaction is carried at 0 °C in the presence of boron trifluoride etherate the cyclization becomes highly stereoselective producing largely a-pipitzol (193) and it has been shown that a stepwise mechanism (195)—K196)->(193) is operative in this case.108... 

The absolute stereochemistries of a- and /3-pipitzol have been unambiguously established as (177) and (178) respectively by the chemical transformation of a-pipitzol into (-)-a-cedrene (179) and by X-ray analysis of a-pipitzol benzoate. ... 

Fraser-Reid s group have described further examples of the use of serial radical cyclization to prepare di- and triquinane natural products. The previously-reported intermediate (4) (Vol. 23, p. 264) has been ring-opened by a Vasella-Bernet reaction, and hence converted to the triquinane (5) with the silphinene skeleton (Scheme 2). Similar initial steps were involved in the conversion of (6) into silphiperfolene (7), and to transform (8) (Vol. 23, p. 265) into (-)-a-pipitzol (9) (mannose carbons numbered). ... 

In addition. Green and Pettus have reported efficient syntheses of a-cedrene, a-pipitzol, and ec-cedrenol on the basis of a novel domino oxidative dearomatization-intramolecular [5+2] cycloaddition-acetic acid addition reaction [96]. Indeed, the key step of the syntheses began with the oxidative dearomatization of ortAo-(pent-4-enyl)-phenols 92, followed by an intramolecular [5+2] cycloaddition of the respective phenoxonium intermediate across the tethered olefin to afford the corresponding tricyclo-[5.3.1.0 ]-undecanes, which finally added acetic acid to provide the final products 93 in low to good yields, as shown in Scheme 20.40. The benzylic... 

Stereocenter effectively guided the formation of the first two stereocenters during the [5+2] reaction. The sequence then terminated with the selective incorporation of acetic acid to generate a third stereocenter, setting it apart from other previous cationic [5+2] reactions. It must be noted that this oxidative dearomatization-induced cascade reaction is unique as it proceeds in the absence of para-oxygen substituent. Starting from tricyclic product 93, the three members of the cedranoid family, a-cedrene, a-pipitzol, and ec-cedrenol, were easily achieved in several supplementary steps. 

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