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

Raceimic 12-amino-6,7,8,1 1-tetrahydro-7,1 1-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 raceimic mixture, were readily converted to the corresponding anti-isomers (huprines) by stereospecific acid-promoted (AICI(3w) 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 situ to the more stable anti-regioisomers (B3LYP/6-31G*). (C) 2001 Elsevier Science Ltd. All rights reserved.