Rathnayake U,
Garner P.
*
Washington State University, Pullman, USA
Asymmetric Synthesis of Lysergic Acid via an Intramolecular (3+2) Dipolar Cycloaddition/Ring-Expansion
Sequence.
Org. Lett. 2021;
23: 6756-6759
DOI:
10.1021/acs.orglett.1c02337
Key words
1,3-dipolar cycloaddition - Oppolzer’s auxiliary - Cossy–Charette ring expansion
Significance
Amide derivatives of lysergic acid have been investigated for the treatment of various
neurological disorders. While many syntheses of lysergic acid itself have been disclosed
previously, Rathnayake and Garner describe a new strategy to afford the enantiopure
piperidine core.
Comment
Using Oppolzer’s camphorsultam auxiliary, an intramolecular 1,3-dipolar cycloaddition
of the in situ generated azomethine ylide and the alkyne established an enantiopure
dihydropyrrole. A subsequent aziridinium-mediated ring expansion then afforded the
piperidine core of lysergic acid.
