Model Construction for the A–B–C Ring System of Lysergic Acid via Vilsmeier–Haack‐Type Cyclization of 1H‐Indole‐4‐propanoic Acid Derivatives

Abstract

AbstractVilsmeier–Haack‐type cyclization of 1H‐indole‐4‐propanoic acid derivatives was examined as model construction for the A–B–C ring system of lysergic acid (1). Smooth cyclization from the 4 position of 1H‐indole to the 3 position was achieved by Vilsmeier–Haack reaction in the presence of K2CO3 in MeCN, and the best substrate was found to be the N,N‐dimethylcarboxamide 9 (Table 1). The modified method can be successfully applied to an α‐amino acid derivative protected with an N‐acetyl function, i.e., to 27 (Table 2); however, loss of optical purity was observed in the cyclization when a chiral substrate (S)‐27 was used (Scheme 5). On the other hand, the intramolecular Pummerer reaction of the corresponding sulfoxide 20 afforded an S‐containing tricyclic system 22, which was formed by a cyclization to the 5 position (Scheme 3).