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

Vilsmeier–Haack ‐type cyclization of 1 H ‐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 1 H ‐indole to the 3 position was achieved by Vilsmeier–Haack reaction in the presence of K 2 CO 3 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 ).