Asymmetric Synthesis of Spiroketals with Aminothiourea Catalysts

• Published in: Angewandte Chemie Vol. 127; no. 51; pp. 15717 - 15720
• Main Authors: Yoneda, Naoki, Fukata, Yukihiro, Asano, Keisuke, Matsubara, Seijiro
• Format: Journal Article
• Language: English; German
• Published: Weinheim WILEY-VCH Verlag 14.12.2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Aminothioharnstoff; Asymmetry; Bark; Cascades; Catalysis; Catalysts; Chemistry; Derivatives; Naturstoffe; Optical activity; Organokatalyse; Pheromones; Reaktionskaskaden; Spiroketale; Synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201508405

Chiral spiroketal skeletons are found as core structures in a range of bioactive compounds. These natural compounds and their analogues have attracted much attention in the field of drug discovery. However, methods for their enantioselective construction are limited, and easily available optically active spiroketals are rare. We demonstrate a novel catalytic asymmetric synthesis of spiroketal compounds that proceeds through an intramolecular hemiacetalization/oxy‐Michael addition cascade mediated by a bifunctional aminothiourea catalyst. This results in spiroketal structures through the relay formation of contiguous oxacycles, in which multipoint recognition by the catalyst through hydrogen bonding imparts high enantioselectivity. This method offers facile access to spiroketal frameworks bearing an alkyl group at the 2‐position, which are prevalent in insect pheromones. Optically active (2S,5S)‐chalcogran, a pheromone of the six‐spined spruce bark beetle, and an azide derivative could be readily synthesized from the bicyclic reaction product. Zweimal gefaltet: Die Titelreaktion verläuft über eine Kaskade aus intramolekularer Halbacetalisierung und Oxy‐Michael‐Addition und führt zu Spiroketalgerüsten mit 2‐Alkyl‐Substitution. Das Borkenkäfer‐Pheromon (2S,5S)‐Chalcogran und ein Derivat sind ausgehend von einem bicyclischen Reaktionsprodukt leicht zugänglich.