Practical Imidazole‐Based Phosphine Ligands for Selective Palladium‐Catalyzed Hydroxylation of Aryl Halides

Abstract

The phenol countdown: Novel imidazole‐based phosphine ligands are synthesized on scales up to 100 g by a convenient lithiation–phosphorylation method. The phosphines are stable towards air and moisture and are successfully applied as ligands in the palladium‐catalyzed selective hydroxylation of aryl halides (see scheme, dba=dibenzylideneacetone).

Selectivity Control in the Palladium-catalyzed Cross-coupling of Alkyl Nucleophiles

“…[12] In this case a complete β-selectivity was observed, independent of the nature of the aryl bromide. A second-generation, N-phenylimidazole-based [13] ligand (L 2 ) was found to be superior to L 1 , and afforded good yields for a range of β-arylated products. Hydrogenation allowed the unveiling of the free amino group, which overall provided an interesting access to analogues of phenylalanine.…”

“…[5] More recently, we have designed a different strategy based on a migratory, 'chain walking' cross-coupling mechanism (Scheme 1b). [6] A functional group bearing a linear alkyl chain is first deprotonated at the acidic α C-H bond, and the resulting carbanionic species reacts with an in situ-generated LPd workers [13] and also known as CataCXium P ® , were found to provide higher migratory aptitude than their biphenyl counterparts.…”

Palladium-catalysed hydroxylation and alkoxylation

“…18 A series of ligands was synthesized and tested in the hydroxylation of aryl halides to explore the influence of the ligand scaffold on the reaction outcome. Two factors were found to be crucial for obtaining reasonable amounts of the product.…”

“…In order to get insight into the reaction mechanism operative in this unprecedented transformation, isotopic labeling studies were performed by running the hydroxyacetoxylation of trans-stilbene in the presence of 18 O-labeled water (20 equiv.) in dry acetic acid (Scheme 17).…”

“…in dry acetic acid (Scheme 17). MS-analysis of the final reaction mixture indicated the major presence of singly 18 O-labeled product (68%). Hydrolysis of the hydroxyacetate product with K 2 CO 3 in methanol afforded the corresponding cis-diol, which was essentially unlabeled (90%).…”