Abstract
(±)‐Desoxynoreseroline (3), the basic ring structure of the pharmacologically active alkaloid physostigmine (1), was synthesized starting from 3‐allyl‐1,3‐dimethyloxindole (9). The latter was prepared from the corresponding 2__H__‐azirin‐3‐amine 6 by a BF~3~‐catalyzed ring enlargement via an amidinium intermediate 7 (Scheme 1). An alternative synthesis of 9 was also carried out by the reaction of N‐methylaniline with 2‐bromopropanoyl bromide (12), followed by intramolecular Friedel–Crafts alkylation of the formed anilide 13 to give Julian's oxindole 11. Further alkylation of 11 with allyl bromide in the presence of LDA gave 9 in an excellent yield (Scheme 3). Ozonolysis of 9, followed by mild reduction with (EtO)~3~P, gave the aldehyde 14, whose structure was chemically established by the transformation to the corresponding acetal 15 (Scheme 4). Condensation of 14 with hydroxylamine and hydrazine derivatives, respectively, gave the corresponding imine derivatives 16a–16d as a mixture of syn‐ and __anti‐__isomers. Reduction of this mixture with LiAlH~4~ proceeded by loss of ROH or RNH~2~ to give racemic 3 (Scheme 5).