On the regioselectivity of the Friedländer reaction leading to huprines: stereospecific acid-promoted isomerization of syn-huprines to their anti-regioisomers

Abstract Racemic 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[ b ]quinoline derivatives ( syn -huprines) substituted at the 9-position with a methyl or ethyl group, and both enantioenriched forms of the 9-ethyl derivative, obtained by chiral MPLC resolution of the racemic mixture, were readily converted to the corresponding anti -isomers (huprines) by stereospecific acid-promoted (AlCl 3 or triflic acid) isomerization of the endocyclic CC double bond from the 9(10)- to the 8(9)-position. These results support the hypothesis that the hitherto unseen syn -huprines are also formed under the usual acidic Friedlander reaction conditions used to prepare the known huprines, but rearrange in…