Practical Total Syntheses of Physostigmines and of Phenserines: A Synopsis

(+/-)-1,3-Dimethyl-3-cyanomethyl-5-methoxyoxindole (8), or (3S)-enriched 8 obtained by asymmetric alkylation, separated into the optically pure enantiomers (8a) and (8b) when chromatographed on a microcrystalline cellulose triacetate (MCTA) column. Asymmetric alkylation of (+/-)-1,3-dimethyl-5-tetrahydropyranyloxyoxindole (6) gave the nitrile (9) ((3S) 66 % ee) which could not be separated on the MCTA column. Optically pure eseroline (17a) was obtained by recrystallization of the fumarate salt (66 % ee) obtained from 9 after reduction with Vitride, reductive N-methylation, and treatment with 2N HCl.