Campus Units

Chemistry, Ames Laboratory

Document Type

Article

Publication Version

Published Version

Publication Date

1-2-2015

Journal or Book Title

Journal of the American Chemical Society

Volume

137

Issue

1

First Page

425

Last Page

435

DOI

10.1021/ja511250m

Abstract

The catalytic addition of alkenes and amines (hydroamination) typically provides α- or β-amino stereocenters directly through C–N or C–H bond formation. Alternatively, desymmetrization reactions of symmetrical aminodialkenes or aminodialkynes provide access to stereogenic centers with the position controlled by the substrate’s structure. In the present study of an enantioselective zirconium-catalyzed hydroamination, stereocenters resulting from C–N bond formation and desymmetrization of a prochiral quaternary center are independently controlled by the catalyst and reaction conditions. Using a single catalyst, the method provides selective access to either diastereomer of optically enriched five-, six-, and seven-membered cyclic amines from aminodialkenes and enantioselective synthesis of five-, six-, and seven-membered cyclic imines from aminodialkynes. Experiments on hydroamination of aminodialkenes testing the effects of the catalyst:substrate ratio, the absolute concentration of the catalyst, and the absolute initial concentration of the primary amine substrate show that the latter parameter strongly influences the stereoselectivity of the desymmetrization process, whereas the absolute configuration of the α-amino stereocenter generated by C–N bond formation is not affected by these parameters. Interestingly, isotopic substitution (H2NR vs D2NR) of the substrate enhances the stereoselectivity of the enantioselective and diastereoselective processes in aminodialkene cyclization and the peripheral stereocenter in aminodialkyne desymmetrization/cyclization.

Comments

Reprinted (adapted) with permission from Journal of the American Chemical Society 137 (2015): 425, doi: 10.1021/ja511250m. Copyright 2015 American Chemical Society.

Copyright Owner

American Chemical Society

Language

en

File Format

application/pdf

Included in

Chemistry Commons

Share

COinS