CO2-Mediated Pd-Catalyzed Stereo- and Regioselective Arylation of Free Allylamines

04 June 2020, Version 3
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Mizoroki-Heck couplings are a powerful method for elaborating alkene feedstocks. While selective functionalization of terminal olefins has been achieved by catalyst design, selective functionalization of internal olefins has generally required use of directing groups except in the case of Michael acceptors. Allylamine substrates have typically required protection to be suitable for these reactions, decreasing the step and atom economy of these procedures. Herein we demonstrate that the addition of CO2 (dry ice) allows for the reproducible stereospecific arylation of both secondary and primary allylamines in the presence of a PdII catalyst. Notably, the product 3,3’-diarylallylamine motif is prevalent in a variety of biologically-relevant structures, and this method represents the most straightforward synthesis of these targets to date. Key features of the method are the ability to access relatively mild conditions that facilitate a broad substrate scope, as well as direct diarylation of terminal allylamine substrates. In addition, several complex and therapeutically-relevant molecules are included to demonstrate the utility of the transformation. Mechanistic studies point to an amine-directed reaction where CO2 serves to protect the substrate and product from degradation.

Keywords

Transient Directing Groups
Alkene Functionalization
Amines
Palladium Catalysis
carbon dioxide (CO2)
Allylamines
Cinnamylamines

Supplementary materials

Title
Description
Actions
Title
SI-Arylation of Allylamines - V3
Description
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.