A practical approach to the fused β-carboline system.: Asymmetric synthesis of indolo[2,3-α]indolizidinones via a diastereoselective intramolecular α-amidoalkylation reaction

Fused beta-carboline systems, as indolo[2,3-a]indolizidinones, indolo[2,3-a]quinolizidinones, their 2-oxa analogues, and benzo[a]indolo[2,3-a]indolizidinones are prepared efficiently via an RLi addition-N-acyliminium ion cyclisation sequence on readily available imides. In an enantioselective variant of these alpha-amidoalkylation reactions, the addition of MeLi to a chiral non-racemic imide derived from tryptophan yielded an oxo amide, which was cyclised diastereoselectively upon treatment with BF3.OEt2, to afford 5,11b-trans-indoloindolizidinone in moderate yield and high ee (99%). (C) 2003 Elsevier Ltd. All rights reserved.