Kinetic resolution of racemic allylic alcohols via iridium-catalyzed asymmetric hydrogenation: scope, synthetic applications and insight into the origin of selectivity

Haibo Wu; Cristiana Margarita; Jira Jongcharoenkamol; Mark D Nolan; Thishana Singh; Pher G Andersson

doi:10.1039/d0sc05276k

Kinetic resolution of racemic allylic alcohols via iridium-catalyzed asymmetric hydrogenation: scope, synthetic applications and insight into the origin of selectivity

Chem Sci. 2020 Dec 8;12(5):1937-1943. doi: 10.1039/d0sc05276k.

Authors

Haibo Wu¹, Cristiana Margarita¹, Jira Jongcharoenkamol¹, Mark D Nolan¹, Thishana Singh², Pher G Andersson^{1

2}

Affiliations

¹ Department of Organic Chemistry, Stockholm University, Arrhenius Laboratory 106 91 Stockholm Sweden pher.andersson@su.se.
² School of Chemistry and Physics, University of Kwazulu-Natal Private Bag X54001 Durban 4000 South Africa.

Abstract

Asymmetric hydrogenation is one of the most commonly used tools in organic synthesis, whereas, kinetic resolution via asymmetric hydrogenation is less developed. Herein, we describe the first iridium catalyzed kinetic resolution of a wide range of trisubstituted secondary and tertiary allylic alcohols. Large selectivity factors were observed in most cases (s up to 211), providing the unreacted starting materials in good yield with high levels of enantiopurity (ee up to >99%). The utility of this method is highlighted in the enantioselective formal synthesis of some bioactive natural products including pumiliotoxin A, inthomycin A and B. DFT studies and a selectivity model concerning the origin of selectivity are presented.