Ullmann‐Goldberg and Buchwald‐Hartwig C−N Cross Couplings: Synthetic Methods to Pharmaceutically Potential N‐Heterocycles

Abstract

The Carbon-Nitrogen bond formation has always been an important and useful tool in drug discovery. Its wide applications in synthesizing N-heterocycles, known as the most prevalent moiety in the active pharmacophores, have attracted increasing attention from researchers. In recent years many works were devoted to finding new and more rapid and effective chemo-and regio-selective methods for the synthesis of N-containing heterocycles. Buchwald-Hartwig and Ullman-Goldberg are two proven efficient methods for synthesizing five, six, and seven-membered heterocycles found abundantly in literature. Here, we study these two amination methods more precisely, based on the reaction conditions and the products.

Mechanochemical C−X/C−H Functionalization: An Alternative Strategic Access to Pharmaceuticals

“…Transition metal‐catalyzed C−N cross‐coupling is an important approach for the construction of nitrogen‐containing bioactive molecules and have been widely used in medicinal chemistry [55] . These methods involves Ullmann‐Goldberg reaction, [25f,56] Buchwald‐Hartwig amination [57] and Chan‐Lam coupling reaction [58] . Among them, Pd‐catalyzed Buchwald‐Hartwig cross‐coupling is at the forefront in practical settings [59] .…”

Blue light enhanced Heck arylation at room temperature applied to allenes

“…10 However, a pivotal role is played by Pd. Named reactions such as Ullmann–Goldberg, Buchwald–Hartwig 14 and aza-Heck 15–17 are frequently applied to form new C–N bonds affording saturated heterocycles.…”

Green-Solvent Selection for Acyl Buchwald–Hartwig Cross-Coupling of Amides (Transamidation)

“…The Buchwald–Hartwig amination has emerged as one of the most central and widely utilized cross-coupling methods in organic synthesis enabling the assembly of key structural motifs in pharmaceuticals, agrochemicals, and natural products. − This class of reactions takes advantage of transition-metal catalysts that operate through the well-defined catalytic cycle and enable C­(sp 2 )–N cross-coupling in a highly predictable manner with excellent functional group tolerance. − …”