Short Total Synthesis of (±)‐γ‐Lycorane by a Sequential Intramolecular Acylal Cyclisation (IAC) and Intramolecular Heck Addition Reaction

• Published in: Chemistry : a European journal 2017-04, Vol.23 (20), p.4750-4755
• Main Authors: Monaco, Alessandra, Szulc, Blanka R., Rao, Zenobia X., Barniol‐Xicota, Marta, Sehailia, Moussa, Borges, Bruno M. A., Hilton, Stephen T.
• Format: Article
• Language: English
• Subjects: Amaryllidaceae Alkaloids - chemical synthesis; Amaryllidaceae Alkaloids - chemistry; Catalysis; Coordination Complexes - chemistry; Coupling; Cyclization; erythrina; Heck reaction; Lewis acid; Lewis acids; Lewis Acids - chemistry; lycoranes; Methodology; Natural products; Palladium - chemistry; Stereoisomerism; Synthesis; Synthesis (chemistry); tandem cyclisation; Utilities
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201700143

An intramolecular acylal cyclisation (IAC) approach to the synthesis of a range of bicyclic heterocycles is reported. As an example of the utility of the IAC reaction, the methodology was applied in a protecting‐group‐free five‐step total synthesis of (±)‐γ‐lycorane, incorporating a new intramolecular Heck addition reaction to generate the pentacyclic core structure of the natural product in good yield. Tandem cyclisation: The pentacyclic structure of the natural product (±)‐γ‐lycorane was synthesized by a new sequential Lewis acid mediated intramolecular acylal cyclisation (IAC)/Heck coupling approach. By using this methodology, a range of bicyclic heterocycles was also synthesized in good yields demonstrating the potential of the IAC reaction to access complex heterocycles (see scheme).