Total Syntheses of Pyroclavine, Festuclavine, Lysergol, and Isolysergol via a Catalytic Asymmetric Nitro-Michael Reaction

5 years ago

Total Syntheses of Pyroclavine, Festuclavine, Lysergol, and Isolysergol via a Catalytic Asymmetric Nitro-Michael Reaction

Subhajit Bhunia, Saikat Chaudhuri, Alakesh Bisai

A catalytic enantioselective construction of vicinal stereocenters is reported. The reaction takes advantage of thiourea-catalyzed intramolecular nitronate addition onto α,β-unsaturated ester to afford exceptional levels of enantioselectivity (up to 97 % ee) with moderate diastereoselectivity (up to 4:1). Using this method, a cross-conjugated ester was synthesized in few steps, from which a 6-endo-trig cyclisation led to the formation of all required functionalities for total syntheses of ergot alkaloids. The strategy not only offers first total syntheses of ergot alkaloids, festuclavine (1 c), and pyroclavine (1 e), and but also an efficient and general approach to other congeners such as, lysergol (1 b), and isolysergol (1 d). Vicinal stereocenter: Unified total syntheses of a number of ergot alkaloids has been envisioned via a key thiourea-catalyzed intramolecular nitronate addition onto α,β-unsaturated ester to achieve exceptional levels of enantioselectivity (up to 97 % ee) with moderate diastereoselectivity (up to 4:1; see scheme). This methodology ensures first total syntheses of pyroclavine (1 e), and festuclavine (1 c), in addition to other congeners such as, lysergol (1 b), and isolysergol (1 d).

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201702459