P-Santalene

The allenic ester 4 of (R)-l also undergoes a highly diastereoselective cycloaddition with cyclopentadiene to afford the e do-adduct 5 almost exclusively and in 99% de. The adduct provides a chiral intermediate to natural (- i-P-santalene (6).-... 

Allenic ester (334), nevertheless, displayed a sufficiently high dienophilicity towards cyclopentadiene to give, in the presence of TiCh(OPr )2, c ro-methylenenorbomene (335) in high yield and stereochemical purity (Scheme 82). The Diels-Alder process (334) -> (335) served as the key step for a synthesis of enantiomerically (-)-P-santalene (337). The conversion of (335) into the natural product involved notably intermediate (336) which, owing to the attached auxiliary, could be efficiently purified by crystallization. 

A number of cycloaddition reactions involving allene derivatives as dienophiles have been recorded. Allene itself reacts only with electron-deficient dienes but allene carboxylic acid or esters, in which a double bond is activated by conjugation with the carboxylic group, react readily with cyclopentadiene to give 1 1 adducts in excellent yield. For example, the allene 12 gave, with very high yield and selectivity, the cycloadduct 13, used in a synthesis of (-)-P-santalene (3.19). An allene equivalent is vinyl triphenylphosphonium bromide, which is reported to react with a number of dienes to form cyclic phosphonium salts. These can be converted into methylene compounds by the usual Wittig reaction procedure (3.20). 

Cleavage of the C-3-C-4 bond of farnesane and connection of new bonds from C-2 to C-4, C-3 to C-7 and C-1 to C-4 lead to bicyclic p-santalane, which is another basic skeleton of substances found in sandalwood. Examples are (-)-p-santalene and (-)-( -p-santalol with a pleasant woody, slightly urinary odor used in perfumes and detergents... 

Independently, Koizumi et al. also reported [160] the use of nonracemic 3-p-tolylsulfinylacrylates as dienophiles in highly diastereoselective Diels-Alder reactions. The functionalized bicyclo[2.2.1]heptane derivatives such as (186), obtained by asymmetric Diels-Alder cycloaddition of ethyl p-tolylsulfinylmethylenepropionate with cyclopentadiene, have been used as intermediates for the synthesis of bicyclic sesquiterpenes such as (+)-epi-P-santalene (187) [161,162] (Scheme 5.61). 

Longifolene thus proved to be a simple elaboration of camphene (4) and structurally close to P-santalene (5). Molecular rotation considerations (75. 14) further showed that (-f )-longifolene is configurationally related... 

Yellow wormwood Artemisia xantaphora) is reported to contain, among other sesqui- and diterpenes, P-santalene (Corey et al., 1962). This bicyclic compound is presumably derived from farnesyl diphosphate by a somewhat more extensive series of rearrangements including those typical of other norbomane-type skeletons. Presumably, a process such as that shown in Scheme 11.62 is involved. 

Scheme 11.62. A representation of a possible route to P-santalene from farnesyl diphosphate.

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