Cetalox and analogues: synthesis via acid-mediated polyene cyclizations.
Using a novel, acid-mediated cyclization methodology, a direct access to Cetalox ((+/-)-1; a commercially important ambergris-type odorant) and various structurally related didehydro (i.e., 19, 26, and 30) and tetradehydro (i.e., 28 and 37/38) analogues is described. Treatment of either (E,E)-14 or (E)-15 with an excess of FSO(3)H in 2-nitropropane at -90 degrees stereospecifically afforded (+/-)-1 in 40 and 42% yield, respectively. Under similar conditions, cyclization of (E)-18 or 20 furnished 19 in 60 and 64% yield, respectively. Analogously, using an excess of ClSO(3)H in CH(2)Cl(2) at -80 degrees, 26 is formed with high stereoselectivity by cyclization of either (E)-24 or (Z)-25 (52 and 31% yield, resp.); in the same manner, 28 was prepared from 27 (22% yield). The same principle was applied to the synthesis of racemic Superambrox (30), via cyclization of 35, but only with poor selectivity (22%) and low yield (7%). Another approach via cyclization of (E)-40 under solvolysis conditions (excess TFA in CH(2)Cl(2) at -10 degrees) gave a higher yield (15%) with improved selectivity (43%). Finally, cyclization of 34 (1:1 diastereoisomer mixture) afforded 37/38 (10:1) in 27% yield. The qualitative organoleptic properties of 19, 26, 28, 30, and 37/38 (10:1) are briefly discussed.
Snowden
Roger L
RL
Firmenich SA, Corporate R&D Division, P. O. Box 239, CH-1211 Geneva 8. roger.snowden@firmenich.com
D003500:Cyclization; D005459:Fluorides / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D010476:Perfume / Q000138:chemical synthesis* / Q000737:chemistry; D011090:Polyenes / Q000737:chemistry*; D013237:Stereoisomerism; D013464:Sulfuric Acids / Q000737:chemistry*
D005663:Furans; D009281:Naphthalenes; D010476:Perfume; D011090:Polyenes; D013464:Sulfuric Acids; C531910:cetalox; C046106:fluorosulfonic acid; D005459:Fluorides