An efficient route for the formal total synthesis of physostigmine (1) and physovenine (2), alkaloids from 5-methoxyindole-3-acetonitrile, through a Grignard reagent 1,4-addition, is described. 2-Hydroxyindolenine 5, the key advanced intermediate for the synthetic targets, was converted either to esermethole (12) via a high-yielding (28%) seven-step sequence or to the C-ring oxygenated analogue 15 in a five-step sequence and 23% overall yield. (1)H NMR and molecular modeling analyses of esermethole (12) and the furoindolines 13 and 15 were used to deconvolute weighted time-average vicinal coupling constants to provide definite solution-state conformational preferences in CD(2)Cl(2) solvent.