Key transformations in a four-step synthesis of the ergot alkaloid scaffold include a novel cesium carbonate-mediated
hydrogen
autotransfer alkylation to generate the C(3)–C(4) bond and
an intramolecular Heck reaction that directly establishes the C(9)–C(10)
alkene of methyl lysergate. An ester reduction and a streamlined experimental
procedure establish a readily scalable, expedient total synthesis
of all four stereoisomers of lysergol and isolysergol, including the
previously unknown (−)-lysergol, for pharmacological evaluation
at 5-HT1A and 5HT2A,B,C receptors. A bicyclic
scaffold is also characterized for the first time in the intramolecular
Heck coupling.