Pd-Catalyzed Amidations of Aryl Chlorides Using Monodentate Biaryl Phosphine Ligands:  A Kinetic, Computational, and Synthetic Investigation

Abstract

We present results on the amidation of aryl halides and sulfonates utilizing a monodentate biaryl phosphine-Pd catalyst. Our results are in accord with a previous report that suggests that the formation of kappa(2)-amidate complexes is deleterious to the effectiveness of a catalyst for this transformation and that their formation can be prevented by the use of appropriate bidentate ligands. We now provide data that suggest that the use of certain monodentate ligands can also prevent the formation of the kappa(2)-amidate complexes and thereby generate more stable catalysts for the amination of aryl chlorides. Furthermore, computational studies shed light on the importance of the key feature(s) of the biaryl phosphines (a methyl group ortho to the phosphorus center) that enable the coupling to occur. The use of ligands that possess a methyl group ortho to the phosphorus center allows a variety of aryl and heteroaryl chlorides with various amides to be coupled in high yield.

Chlorophenols in organic synthesis

“…The high yields were observed with low amounts of reagents, except the reaction with carboxamide [38].…”

“…Изучением этих реакций занималась группа исследова-телей под руководством S. L. Buchwald [38]. Сначала было изучено влияние различных условий на амидирование хлоранизолов 1b с бензамидом 40 с участием палладиевого катализатора и лиганда L4.…”

An Improved Synthesis of Imidazo[4,5‐b]pyridines and Imidazo[4,5‐b]pyrazines by Palladium Catalyzed Amidation using Xantphos in a 1,4‐Dioxane:tert‐Amyl Alcohol Solvent System

“…Conversely, bidentate phosphine ligands required the use of aprotic solvents for positive outcomes with little to no conversion observed in alcoholic solvents. [12,[25][26][27][28][29] Re-examination of our reaction revealed that XantPhos and DPEPhos in aprotic solvents produced the desired cyclization product 2a along with reduced pyridine 3 (entries 1-5, Table 1). The identity of 3 was confirmed through independent synthesis from 3-aminopyridine.…”

[3a,4]-Dihydropyrazolo[1,5a]pyrimidines: Novel, Potent, and Selective Phosphatidylinositol-3-kinase β Inhibitors

“…We were particularly interested in analogues, which modulated the basicity of the morpholine either by replacing the nitrogen or by converting it to an amide. The tetrahydropyranyl and pyridyl analogues 5a and 5e were prepared from the corresponding β-keto esters, and the morphlin-3-one analogue 5b was prepared via a Buchwald amidation 23 of the 5-chloro-7-hydroxypyrazolopyrimidone intermediate. The enzymatic activity of these analogues is shown in Table 2.…”