Model Construction for the A–B–C Ring System of Lysergic Acid Via Vilsmeier–Haack‐Type Cyclization of 1h‐indole‐4‐propanoic Acid Derivatives

Vilsmeier-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 a-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).