East Indian sandalwood oil. 1. Stereoselective synthesis of (.+-.)-.beta.-santalene and (.+-.)-.beta.-santalol

Challenges in the Synthesis of Natural and Non‐Natural Volatiles

“…56 Macrocyclic musks in a pure form such as muscone (88) have been used in perfumery virtually since their structural determination by Ruzicka in 1926 and despite their high initial price. 56 The efficient synthesis of these large macrocyclic rings has been the subject of constant research and, in a novel three-step synthesis of racemic muscone (88), the radical mediated addition of acetone to 1, 9-decadiene (89) gave the diketone 90 (Scheme 7.18).…”

“…56 The efficient synthesis of these large macrocyclic rings has been the subject of constant research and, in a novel three-step synthesis of racemic muscone (88), the radical mediated addition of acetone to 1, 9-decadiene (89) gave the diketone 90 (Scheme 7.18). 57 Intramolecular aldol condensation of the diketone 90 followed by hydrogenation gave racemic muscone (88). The asymmetric hydrogenation of the pure (E)-and (Z)-isomers of enone 91 had previously been applied to the synthesis of (R)-muscone (88).…”

“…57 Intramolecular aldol condensation of the diketone 90 followed by hydrogenation gave racemic muscone (88). The asymmetric hydrogenation of the pure (E)-and (Z)-isomers of enone 91 had previously been applied to the synthesis of (R)-muscone (88). 58 Using another related aldol approach, non-natural unsaturated analogues such as (5Z)-muscenone (92) have been synthesised in stereoselective and enantioselective fashion (Scheme 7.19) confirming their highly appreciated nitro musk aspects.…”

“…86 For the industrial synthesis of the more appreciated (Z)-(À)-b-santalol (42) several challenges must be overcome, including the selective synthesis of the (Z)-allylic alcohol, the installation of the exo sidechain and the exo methylene functional group, whilst avoiding the facile rearrangement of the norbornane skeleton under acidic conditions. Despite many racemic, academic syntheses, 87 an asymmetric synthesis 85 and two theoretically industrially feasible racemic syntheses of (Z)-(À) -b-santalol (42) by Christenson and Willis (1979) 88 and Baumann and Hoffmann (1979), 89 neither synthetic (AE)-(Z)-a-santalol (119) nor (AE)-(Z) -b-santalol (42) are available commercially. Christenson and Willis described the racemic synthesis of 42 via buffered epoxidation of racemic camphene (122) followed by epoxide opening with the dianion of acetic acid and ring closure giving the spirolactone 123 (Scheme 7.20).…”

“…Christenson and Willis described the racemic synthesis of 42 via buffered epoxidation of racemic camphene (122) followed by epoxide opening with the dianion of acetic acid and ring closure giving the spirolactone 123 (Scheme 7.20). 88 Sulfuric acid mediated rearrangement gave the fused lactone 124 containing the three carbon atom-containing sidechain with the required exoconfiguration. Heating under acidic alcoholic conditions cleaved the lactone and generated the exo-methylene functionality in ester 125.…”