Submission Date

4-28-2025

Document Type

Paper- Restricted to Campus Access

Department

Chemistry

Adviser

Julianne Yost

Committee Member

Amanda Reig

Department Chair

Mark Ellison

External Reviewer

Graham E. Dobereiner

Distinguished Honors

This paper has met the requirements for Distinguished Honors.

Project Description

Buchwald-Hartwig aminations form new C–N bonds by coupling an aryl halide with an amine. Due to the nature of this reaction, using traditional synthetic routes to conduct amination reactions on indoles generally includes protecting the indole N–H, carrying out the cross-coupling reaction, and then deprotecting. Such sequences are long and are not necessarily functional group tolerant. To date, although Buchwald-Hartwig aminations on unprotected, functionalized indoles have been reported, few such transformations containing reactive moieties have been studied. Therefore, novel methods for amination reactions are needed to keep reaction sequences short with high atom economy. This study explored the development of a Buchwald-Hartwig amination to couple an amine with an unprotected, functionalized indole. Overall, a method was developed to install a primary, aromatic amine in moderate yield. Scope of both the amine coupling partner and bromoindole was investigated. Additionally, proof of concept for a greener transformation, as well as methods for the installation of secondary and benzylic amines were provided. Future studies will include optimizing the work-up procedure to isolate the desired compounds in high yield. Continued progression towards a greener transformation, mechanistic studies, and scope of the reaction with additional amines are also underway.

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