Total syntheses of (+/-)-axamide-1 and (+/-)-axisonitrile-1 via 6-Exo-dig radical cyclization.
Total syntheses of (+/-)-axamide-1 (1) and (+/-)-axisonitrile-1 (2) were accomplished by using the alpha-carbonyl radical cyclization as the key step. Thienylcyanocuprate 24 mediated conjugated addition of 5-(trimethylsilyl)-4-pentynylmagnesium chloride (23) to 3-methylcyclopenten-1-one (22) and subsequent treatment with TMSCl afforded silyl enol ether 25. Iodination of 25 with NaI and m-CPBA afforded alpha-iodoketone 21. 6-Exo-dig radical cyclization of 21 and subsequent desilylation furnished hydroindane derivative 20. Bicyclic ketone 20 was converted to nitrile 19 via a three-step sequence involving Luche reduction, mesylation, and S(N)2 substitution reaction. Finally, tandem alkylation-reduction on nitrile 19 and subsequent functional group transformations afforded (+/-)-axamide-1 (1) and (+/-)-axisonitrile-1 (2).
Kuo
Yuan-Liang
YL
Department of Chemistry, National Tsing Hua University, Hsinchu 300, Taiwan, ROC.
Dhanasekaran
Manickam
M
Sha
Chin-Kang
CK
D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D005609:Free Radicals; D012717:Sesquiterpenes; C551684:axamide 1; C551683:axisonitrile 1