Dearomative Spirocyclization of Ynamides

07 August 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Spiro N-heterocycles, particularly aza-spiro piperidines, have shown significant promise in pharmaceutical applications due to their ability to enhance physicochemical properties. Despite their potential, the preparation of these complex structures poses significant challenges. To address this, we propose a one-pot dearomative spirocyclization reaction of ynamides. This method involves a copper-catalyzed carbomagnesiation reaction, achieving chemo-, regio-, and stereoselective formation of (Z)-vinyl metal intermediates. Upon the addition of a Lewis acid, these intermediates undergo a regioselective nucleophilic dearomatization event, facilitating the synthesis of diverse aza-spiro piperidine scaffolds with multiple functional handles. Various Grignard reagents, diverse ynamides, and acylating reagents, have been explored, producing complex spirocyclic structures with potential medicinal relevance.

Keywords

Dearomative functionalization
Carbometalation
Ynamides
Heterocycles
Functional molecules

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.