Asymmetric Synthesis of Spiroketals with Aminothiourea Catalysts. Issue 51 (29th October 2015)

• Record Type: Journal Article
• Authors: Yoneda, Naoki; Fukata, Yukihiro; Asano, Keisuke; Matsubara, Seijiro
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 51(2015)
• Page Start: 15497
• Page End: 15500
• Publication Date: 2015-10-29
• Subjects: aminothiourea -- cascade reactions -- natural products -- organocatalysis -- spiroketals; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201508405
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 (2 S, 5 S )‐chalcogran, a pheromone of the six‐spined spruce bark beetle, and an azide derivative could be readily synthesized from the bicyclic reaction product. Abstract : Around and around : A catalytic asymmetric synthesis of spiroketals through an intramolecular hemiacetalization/oxy‐Michael addition cascade with a bifunctional aminothiourea catalyst was developed. This method offers facile access to spiroketal frameworks bearing an alkyl group at the 2‐position. Optically active (2 S, 5 S )‐chalcogran, a pheromone from the six‐spined spruce bark beetle, and a derivative were readily synthesized from the bicyclic reaction product.