Synthesis of a-Santalol

10-bromocamphor (6.13) can then be treated with potassium hydroxide in a nucleophilic substitution reaction to give 10-hydroxycamphor (6.14). 

The answer, of course, is that the natural material is the Z-isomer, whereas Guha and Battacharyya had synthesised the F-isomer. There was nothing that they could do about this at that time. In 1944, the only method for selective synthesis of Z-isomers of olefins was the Lindlar hydrogenation of acetylenes and that is clearly inappropriate in this instance as the target is a trisubstituted olefin. Lindlar hydrogenation is only suitable for the synthesis of 1,2-disubstituted Z-olefins. 

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Further studies on the biosynthesis of ovalicin (57) have demonstrated the use of deuterium magnetic resonance in biosynthetic studies. Compounds (59)—(62), structurally related to (-)-a-santalene (58), have been isolated from the essential oil of Lavandula ojficinalis and L. hybrida " An alternative synthesis of a-santalol... 

In the course of developing stereospecific routes to trisubstituted double bonds, Corey et al. have completed an efficient synthesis of a-santalol (132), many stages of which involve recent synthetic techniques from Corey s laboratory. Thus (—)-7r-bromotricyclene (133) was converted into (134) by successive treatment with lithio-l-trimethylsilylpropyne, silver nitrate (desilylation), and potassium... 

Total synthesis of a-santalol.2 a-Santalol (7) has been synthesized from (—)-ir-bromotricyclene (1) by essentially the same procedure used previously by Corey and Kirst for the synthesis of trans,frans-farnesol (2, 240-241). The starting material was converted into the terminal acetylene (2) by reaction with lithio-1-trimethylsilylpropyne followed by desilylation (2, 239-240). This was converted into the propargylic alcohol (3) by way of the lithium derivative by reaction with paraformaldehyde. /run.v-Hydroaluruination was then effected by treatment with H-buty(lithium followed by diisobutylaluminum hydride. Treatment with iodine... 

Tricyclanes and Quadricyclanes.—A new synthesis of a-santalol (466) has been described. Reaction of the (7r-allyl)nickel bromide complex (464) with the bromotri-cyclene (465) gave the benzyl ether (467) and its -isomer. Reductive cleavage with... 

Electrophilic species, other than a proton, can be used, thus adding to the synthetic utility of this variation. One such example is the end-game solution to the total synthesis of a-santalol 61. ° The advanced intermediate 60 was treated with ylide 16. Formation of the P-oxido ylide with -BuLi and addition of formaldehyde provided a one-step procedure for alkene formation and elaboration to 61. 

A facile synthetic route to a-santalol (105) from the previously known aldehyde (106) has been reported by Corey et a/. in which a stereospecific modified Wittig reaction [(i) ethylidenetriphenylphosphorane, (ii) n-butyl-lithium, and (iii) paraformaldehyde] yielded the desired cis-isomer. Erman and co-workers, in a continuation of their synthetic work on the santalols, have reported the preparation of -santalol (107) from 3-methylnorcamphor. The route also provided a sample of the tmns-isomer which had previously been considered to be the natural isomer. The use of a borate ester as a protecting group for a hydroxy-function facilitated the synthesis of dihydro- -santalol (108) as outlined in Scheme 3. (These borate esters are stable to anhydrous acid or base but are readily hydrolysed in aqueous media.)... 

This reaction has been used or h synthesis of tricyclo-efca-santalol (3), a minor constituent of sandalwood oil (equation I). 

This sequence was used in a remarkably simple synthesis of the essential oil constituent a-santalol (6) from the aldehyde (5). This substance had been synthesized previously by the reaction of (5) with (carboethoxyethylidene)triphenyl-... 

The complete details of the chemistry and synthesis of copabomeol (97) have been described by Kolbe-Haugwitz and Westfelt. The starting material was a commercial sample of santalol (a Pca.l 3), which was converted to a mixture of syn and anti keto-esters (98) and (99) of which only the syn isomer (98) underwent a Michael cyclisation to the tricyclo-keto-ester (100). Conversion of the... 

The dione (100) reacted exclusively at the exocyclic carbonyl in a synthesis of methyl 9-cis- (101) and 9-rra/i5 -trisporates B. Although ( )-dihydro-j8-santalol (103) was obtained from (102) in 90% yield if the hydroxy-group was protected as the borate ester, use of unprotected (102) gave predominantly the isomeric olefin (104). Similarly the hydroxy-ketone (105) gave the olefin (106), but similar rearrangements did not occur using the isopropylidene- or ethoxycarbonylmethylene-phosphoranes. 

The complete details of the synthesis of racemic dihydro-) -santalol (66) have been published. A new three-step synthesis of j8-santalene (71) has been... 

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