119124-76-4Relevant articles and documents
Short Total Syntheses of (+/-)-Sativene and (+/-)-cis-Sativenediol
Sigrist, von Rolf,Rey, Max,Dreiding, Andre S.
, p. 788 - 807 (2007/10/02)
Our approach to (+/-)-sativene (7) and (+/-)-cis-sativenediol (9) involves: a) reaction of 3-methylbutanoyl chloride with Et3N/cyclopentadiene to give the endo-isopropyl-ketone 1 (here improved to 71percent), b) NBS bromination of 1 to a 5:1 mixture (87percent) of the bromo-ketones 2 and 3, c) NFD-reaction sequence initiated by the attack of 1,2-butadienyl titanate (complex of 15, obtained from 2-butine) on 2/3 to afford 52percent of the brexenone derivative 4 (along with 8percent of its epimer 16), d) addition of dibromomethane to 4 forming 63percent of the diene-alcohol 5 (along with 13percent of the diene-carbaldehyde 38), and e) carbenoid ring-expansion with MeLi applied to 5 resulting in 41percent the diene-ketone 6 (along with 15percent of a 1:3 mixture of the diene-ketones 32 and 33).Wolff-Kishner reduction of 6 led to 81percent of (+/-)-sativene (7), when enough O2 was present, but to 97percent of the diene 8 in the strict absence of O2. (+/-)-cis-Sativenediol (9) was obtained (86percent) by OsO4 hydroxylation of 8.The brexenone derivatives 4 and 16 (6:1, 50percent) were also produced when the NFD-reaction sequence was applied to the isomeric bromo-ketone mixture 13/14 (1:3).The latter was obtained by NBS bromination of 10, which in turn was available by base epimerization of 1, followed by destructive removal of unreacted 1 by repeated gas-flow thermolysis.An analogous (less convenient) route to (+/-)-sativene (7) passed through a series of dihydro compounds (the ene series); it started with the methylidene-ketone 36, which was the product (97percent) of a partial hydrogenation of 4.Addition of dibromomethane to 36 led to 62percent of the methylidene-alcohol 39 (along with a little tetracyclic ether 40).Carbenoid ring expansion of 39 with MeLi afforded ca. 42percent of the methyldene-ketone 41 (along with 7percent of the methylidene-ketone 43 or, under slightly different conditions, along with 9percent of the methylidene-ketone 42 and 10percent of the methylidene-carbaldehyde 44).The methylidene-alcohol 39 and the methylidene-ketone 43 were also obtained by partial hydrogenation of 5 and 33, respectively.Wolff-Kishner reduction converted 41 into (+/-)-sativene (7, 99percent); the same conditions applied to 42 afforded only ca. 8percent 7 (along with three other hydrocarbons, one of them (ca. 21percent) probably being (+/-)-copacamphene (45)).In the diene series, the two succeeding reactions (4 -> 5 and 5 -> 6) competed with the same side reaction, a rearrangement leading to the brendene-aldehyde 38.In the ene series, the corresponding dihydro-by-product 44 was found in the reaction 39 -> 41, but not during 36 -> 39.These side reactions could largely be suppressed by keeping the reaction temperature low.An explanation is proposed.
