ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
Short Total Syntheses of (±)-Sativene and (±)-cis-SativenediolOur approach to (±)-sativene (7) and (±)-cis-sdtivenediol (9) involves: (a) reaction of 3-methylbutanoyl chloride with Et3N/cyclopentadiene to give the endo-isopropyl-ketone 1 (here improved to 71%), (b) NBS bromination of 1 to a 5:1 mixture (87%) 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 52% of the brexenone derivative 4 (along with 8% of its epimer 16), (d) addition of dibromomethane to 4 forming 63% of the diene-alcohol 5 (along with 13% of the diene-carbaldehyde 38), and (e) carbenoid ring-expansion with MeLi applied to 5 resulting in 41% the diene-ketone 6 (along with 15% of a 1:3 mixture of the diene-ketones 32 and 33). Wolff-Kishner reduction of 6 led to 81% of (±)-sativene (7), when enough O2 was present, but to 97% of the diene 8 in the strict absence of O2. (±)-cis-Sativenediol (9) was obrained (86%) by OsO4 hydroxylation of 8. The brexenone derivatives 4 and 16 (6:1, 50%) were also produced when the NFD-reaction sequence was applied to the isomeric bromo-ketone mixture 13/13 (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 (97%) of a partial hydrogenation of 4. Addition of dibromomethane to 36 led t 62% of the methylidene-alcohol 39 (along with a little tetracyclic ether 40). Carbenoid ring expansion of 39 with MeLi afforded ca. 42% of the methylidene-ketone 41 (along with 7% of the methylidene-ketone 43 or, under slightly different condition, along with 9% of the methylidene-ketone 42 and 10% of the methylidene-carabaldehyde 44). The methylidene-alcohol 39 and the methylidene-ketone 43 were also obtained by partial hydrogenation of 5 and 33, respectively. Wolff-Kisher reduction converted 41 into (±)-sativene (7 99%); the same conditons applied to 42 afforded only ca. 8% 7 (along with three other hydrocarbons, one of them (ca. 21%) 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 reacton 39→41, but not during 36→39. These side reactons could largely be suppressed by keeping the reaction temperature low. An explanation is proposed.
Additional Material:
1 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19880710414
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