Total Syntheses of (±)-Axamide-1 and (±)-Axisonitrile-1 via 6-<i>Exo-dig</i> Radical Cyclization

Abstract

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).