Synthesis and Transformations of Ethyl 3-Formyl-1H-indole-2-carboxylate. Preparation of Aplysinopsin and β-Carboline Thiohydantoin Analogues*

Recently, a series of alkyl 2-substituted 3-(dimethylamino)prop-2-enoates and related enaminones have been prepared as versatile reagents for the preparation of various dehydroalanine derivatives, heterocyclic systems, and natural product analogues. In extension, chiral cyclic enamino lactams and lactones, derived from α-amino acids and (+)-camphor have been used in the synthesis of functionalised heterocycles, such as heteroarylalanines, heteroarylalaninols, heteroarylpropanediols, 3-heteroaryl-(+)-camphors, and heterocyclic compounds with an α-amino acid or a dipeptide structural element incorporated into the ring system [1, 2]. Recently, alkyl 2-substituted 3-(dimethylamino)prop-2-enoates and related enaminones have been employed in combinatorial synthesis of heterocycles and N-acyldehydroalanine esters [3] and in the synthesis of natural product analogues, such as aplysinopsins [4], meridianins [5], and dipodazines [6]. 3-(Dimethylamino)prop-2-enoates and their chiral analogues are usually prepared by treatment of a suitably functionalised methylene compound with formamide acetal, e.g. with N,N-dimethylformamide dimethyl acetal (DMFDMA) or with tert-butoxybis(dimethylamino)methane (Bredereck’s reagent) [1].