Enantioselective Alkoxycyclization of 1,6‐Enynes with Gold(I)‐Cavitands: Total Synthesis of Mafaicheenamine C

• Published in: Angewandte Chemie 2021-04, Vol.133 (17), p.9425-9430
• Main Authors: Martín‐Torres, Inmaculada, Ogalla, Gala, Yang, Jin‐Ming, Rinaldi, Antonia, Echavarren, Antonio M.
• Format: Article
• Language: English
• Subjects: alkoxycyclization; asymmetric synthesis; Carbazole; Carbazoles; Chemistry; Enantiomers; Gold; gold(I) cavitands; Isomerization; natural product synthesis; Synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202017035

Chiral gold(I)‐cavitand complexes have been developed for the enantioselective alkoxycyclization of 1,6‐enynes. This enantioselective cyclization has been applied for the first total synthesis of carbazole alkaloid (+)‐mafaicheenamine C and its enantiomer, establishing its configuration as R. The cavity effect was also evaluated in the cycloisomerization of dienynes. A combination of experiments and theoretical studies demonstrates that the cavity of the gold(I) complexes forces the enynes to adopt constrained conformations, which results in the high observed regio‐ and stereoselectivities. A new family of chiral gold(I)‐cavitand complexes was designed and applied to the development of the first enantioselective alkoxycyclization of phenyl‐linked 1,6‐enynes, giving high enantioselectivities and excellent yields. This approach was used for the first total synthesis of carbazole alkaloid (+)‐mafaicheenamine C. The cavity effect was studied theoretically supporting the high regio‐ and stereoselectivities.