Simplifying the Synthesis of Nonproteinogenic Amino Acids via Palladium-Catalyzed δ-Methyl C-H Olefination of Aliphatic Amines and Amino Acids

Trisha Bhattacharya; Prabhat Kumar Baroliya; Shaeel A Al-Thabaiti; Debabrata Maiti

doi:10.1021/jacsau.3c00215

Simplifying the Synthesis of Nonproteinogenic Amino Acids via Palladium-Catalyzed δ-Methyl C-H Olefination of Aliphatic Amines and Amino Acids

JACS Au. 2023 Jun 22;3(7):1975-1983. doi: 10.1021/jacsau.3c00215. eCollection 2023 Jul 24.

Authors

Trisha Bhattacharya¹, Prabhat Kumar Baroliya^{1

2}, Shaeel A Al-Thabaiti³, Debabrata Maiti¹

Affiliations

¹ Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
² Department of Chemistry, Mohanlal Sukhadia University, Udaipur 313001, India.
³ Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia.

Abstract

Transition metal-catalyzed directing group assisted C-H functionalizations provide a straightforward access to a wide variety of nonproteinogenic amino acids. While altering the side chain of an existing natural amino acids is one way, introducing a functional group to an aliphatic amine to synthesize versatile unnatural amino acids is another exciting avenue. In this work, we explore both the possibilities by the palladium-catalyzed δ-C(sp³)-H olefination of aliphatic amines and amino acids. A diverse substrate scope including sequential difunctionalizations followed by post synthetic transformations were achieved to understand the applicability of the current protocol. An in-depth mechanistic study was carried out to learn the mode of the reaction pathway.