Synthetic Strategies toward Lysergic Acid Diethylamide: Ergoline Synthesis via α-Arylation, Borrowing Hydrogen Alkylation, and C-H Insertion.
The Journal of organic chemistry October 6, 2023 Jeremy R Tuck, Lee E Dunlap, David E Olson 7 citations
A novel seven-step formal synthesis of LSD has been developed, focusing on connecting the A- and D-rings first and then bridging the B- and D-rings last. The synthesis uses cross-coupling, intramolecular α-arylation, borrowing hydrogen alkylation, and rhodium-catalyzed C-H insertion to form the tetracyclic ergoline core. The methods enable the first introduction of substitutions on the C-ring, though each strategy faces unique challenges when elaborating to ergoline natural products. These findings provide insights that will guide future synthetic strategies toward ergolines and related compounds.