Pergamon Tetrahedron Letters 41 (2000) 1993–1996 TETRAHEDRON LETTERS N-Acyliminium ion cyclisation versus rearrangement. The synthesis of 13,13-dimethylberberines and 3,4-dimethylisoquinolin-1-ones Harry Heaney * and Mutasem O. Taha Department of Chemistry, Loughborough University, Loughborough, Leicestershire LE11 3TU, UK Received 18 November 1999; accepted 11 January 2000 Abstract The regioselective reduction of a range of N-substituted-4,4-dimethylhomophthalimide derivatives gave the related carbinol amides that function as acyliminium ion precursors in the presence of Lewis or protic acids; the fate of the acyliminium ions is determined in part by the nucleophilicity of the β-arylethyl group on nitrogen, the electrophile used to generate the ion, and the precise reaction conditions and led either to cyclisation reactions or methyl migration. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: amido-alcohols; cyclisation; diastereoselection; nitrogen heterocycles. The chemistry of acyliminium ions has been studied in considerable detail during the past two decades, 1 and the method continues to attract considerable attention. 2 A number of research groups have used the chemistry of acyliminium ions in routes to alkaloids or in the synthesis of compounds with potential biological activity. 3 Other targets have included isoquinolones by Friedel–Crafts amidoacylation reactions, 4a and antagonists of platelet aggregation. 4b Our interest in this area is concerned with both mechanistic and synthetic applications of acyliminium ions. 5 Our most recent work has been concerned with ring annelated tetrahydroisoquinolin-1[2H]-ones in which a key synthetic step involved 1,2-alkyl-shifts involving cations derived from 4,4-dialkyl-3-hydroxy-3,4-dihydroisoquinolin- 1[2H]-one derivatives. 5c A limited number of cyclisation reactions of N-β-arylacyliminium ions have been reported. 6 We now describe the use of a number of protic and Lewis acids in reactions of carbinolamides that result in the formation of 13,13-dimethylberberine derivatives and 3,4- dimethylisoquinolones. The carbinolamides were prepared in three steps from commercially available homophthalic anhydride. Heating the anhydride with a variety of arylalkylamines at 200°C for 90–120 min gave the homophthalimide derivatives (1a–e) in yields ranging from 31 to 92%. The methylation of the compounds (1a–e) was carried out in aqueous ethanolic sodium hydroxide solution with an excess of * Corresponding author. Fax: 44 + 1509 223925; e-mail: h.heaney@lboro.ac.uk (H. Heaney) 0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(00)00081-2 tetl 16359