The feasibility of the proposed intramolecular cascade was first tested in the setting of a racemic synthesis of akuammicine (Fig. ). The required thiophene S,S-dioxide 8 was synthesised from the corresponding commercially-available 2-chlorothiophene ester via peroxyacid oxidation , while the synthesis of the indole dienophile 9 involved a simple N-alkylation of tryptamine with known sidechain 10 (prepared in two steps) . With these building blocks in hand, the key halide substitution / intramolecular cycloaddition / cheletropic extrusion cascade was investigated. Reaction of TDO 8 with amine 9 at room temperature, followed by warming to 75 °C, efficiently furnished the cycloaddition cascade product 11. Reduction of the enamine in 11 proved challenging; the combination of acetic acid and sodium cyanoborohydride at 65 °C was found to afford the desired diastereomer 12 and its epimer 12' in 63% overall yield (1:2.4 dr), in favour of 12' selectivity of this step likely derives from the preferred delivery of hydride to the less-hindered concave face of the intermediate iminium ion. We nonetheless found that this three step sequence could be streamlined by performing the enamine reduction in the same reaction flask immediately after the cycloaddition, such that the synthesis of 12/12' could be achieved in 62% combined yield from 9. An intramolecular Heck reaction of the desired isomer 12 (81%) completed the synthesis of akuammicine in three steps from tryptamine (five steps in the longest linear sequence (LLS) that includes assembly of the sidechain 10). This route represents the most concise assembly of (±)akuammicine to date and, aside from the use of organic solvents, also avoids the formation of any carbon-containing waste.