Enantioselective Synthesis of N,S-Acetals by an Oxidative Pummerer Type Transformation Using Anionic Phase-Transfer Catalysis

• Published in: Angewandte Chemie International Edition 2017-12, Vol.57 (2), p.589-593
• Main Authors: Biswas, Souvagya, Kubota, Koji, Orlandi, Manuel, Turberg, Mathias, Miles, Dillon H., Sigman, Matthew S., Dean Toste, F.
• Format: Article
• Language: English
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201711277

We report the first enantioselective oxidative Pummerer-type transformation using anionic phase-transfer catalysis, resulting in the formation of enantioenriched sulfur bearing heterocycles. This reaction includes the direct oxidation of sulfides to the thionium intermediate, followed by an asymmetric intramolecular nucleophilic addition to form the chiral cyclic N,S-acetals with moderate to high enantioselectivites. Deuterium labelling experiments were performed to identify the stereodiscrimination step of this process. Further analysis of the reaction transition states by means of multidimensional correlations and DFT computations highlight the existence of a set of weak noncovalent interactions between the catalyst and substrate that governed the enantioselectivity of the reaction. The first catalytic enantioselective Pummerer type transformation has been developed employing chiral anion phase-transfer catalysis. This chemical transformation allows the facile construction of a wide variety of enantioenriched cyclic N,S -acetal motifs that were previously difficult to access.