Synthetic Efforts toward Akuammiline Alkaloids from Tetracyclic 6,7-Seco Derivatives

Abstract

The addition of enolates derived from indole-3-acetic esters 1 − 3 to pyridinium salts 4, 23, and 24, followed by acid cyclization of the resulting 1,4-dihydropyridines, leads to tetrahydro-1,5-methanoazocino[3,4- b ]indoles 5 − 7, 25 − 27, which have been subsequently elaborated into 4 E -ethylidene(or 4α-ethyl)-hexahydro-1,5-methanoazocino[3,4- b ]indoles. Closure of the six-membered C ring of akuammiline alkaloids by formation of C-6/C-7 bond from appropriately N (b) -substituted derivatives of these tetracyclic ABDE substructures has been extensively investigated. In the N -unsubstituted indole series, both cyclization of thionium ions generated either by Pummerer reaction from sulfoxide 16 or by DMTSF treatment of dithioacetal 36 and photocyclization of chloroacetamide 47 occur upon the indole nitrogen to give pentacycles 18, 38, and 49, respectively. When the indole nitrogen is blocked by a substituent, the thionium ions derived from sulfoxides 17 and 43 and dithioacetals 37 and 44 do not cyclize and lead to different products depending on the reaction conditions, whereas chloroacetamides 48 and 51 undergo a reductive photodehalogenation. Attempted radical cyclization of seleno derivatives 53, 55, and 56 under a variety of conditions gives the corresponding reduced products. Finally, attempted photoisomerization of 1-acylindole 62 leads to the N (b) -methyl tetracycle 63 .