Kinetic and Dynamic Kinetic Resolution of Racemic Tertiary Bromides by Pentanidium-Catalyzed Phase-Transfer Azidation

Jingyun Ren; Xu Ban; Xin Zhang; Siu Min Tan; Richmond Lee; Choon-Hong Tan

doi:10.1002/anie.202000138

Kinetic and Dynamic Kinetic Resolution of Racemic Tertiary Bromides by Pentanidium-Catalyzed Phase-Transfer Azidation

Angew Chem Int Ed Engl. 2020 Jun 2;59(23):9055-9058. doi: 10.1002/anie.202000138. Epub 2020 Mar 24.

Authors

Jingyun Ren^{1

2}, Xu Ban², Xin Zhang², Siu Min Tan³, Richmond Lee³, Choon-Hong Tan²

Affiliations

¹ Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi, 710127, P. R. China.
² Division of Chemistry and Biological Chemistry, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore, Singapore.
³ Science and Mathematics Cluster, Singapore University of Technology and Design, 8 Somapah Road, Singapore, 487372, Singapore.

PMID: 32125069
DOI: 10.1002/anie.202000138

Abstract

We have developed a method to afford enantiomerically enriched tertiary azides and bromides through pentanidium-catalyzed kinetic resolution (KR) of racemic tertiary bromides under base-free conditions. We found that the absence of water is crucial to attain a high selectivity factor (s). On the other hand, new experimental observations and DFT modeling led us to propose that enantioconvergent azidation of tertiary bromides proceeded through dynamic kinetic resolution (DKR). The investigations particularly identified the crucial roles of base and water in the enantioconvergent process, thus supporting the proposal that the tertiary bromide isomerizes in the presence of base and water through a S_N 2X pathway.

Keywords: SN2X substitution; asymmetric catalysis; dynamic kinetic resolution; kinetic resolution; pentanidium catalysts.

Publication types

Research Support, Non-U.S. Gov't