A Novel Synthetic Approach to (±)‐Desoxynoreseroline

(±)‐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 ).