Pd‐PEPPSI‐IPent: An Active, Sterically Demanding Cross‐Coupling Catalyst and Its Application in the Synthesis of Tetra‐Ortho‐Substituted Biaryls

Abstract

Incredible Bulk: A series of N-heterocyclic carbene catalysts (see picture) were prepared and evaluated in the Suzuki-Miyaura reaction. A variety of sterically encumbered tetra-ortho-substituted biaryl products were formed from unreactive aryl chlorides using the isopentyl-substituted catalyst at temperatures ranging from 65 degrees C to room temperature. The cyclopentyl-substituted catalyst was virtually inactive, demonstrating that "flexible bulk" is essential to promote these transformations.

An N-heterocyclic carbene-palladium-η3-allyl chloride complex for the Suzuki-Miyaura coupling of aryl halides

“…This fact could explain why the catalyst is active for aryl bromides and activated aryl chlorides, but moderately active for non-activated aryl chlorides, under the conditions employed. In fact, catalysts with more sterically demanding ligands are more active even for sterically demanding aryl chlorides [32,33]. The bulkiness around the metal could be responsible for the catalytic activity of the complex.…”

Metal Complexes of Very Bulky N,N′‐Diarylimidazolylidene N‐Heterocyclic Carbene (NHC) Ligands with 2,4,6‐Cycloalkyl Substituents

“…The synthesis of the respective gold complexes [(5a)AuCl] and [(5b)AuCl] was possible, which in turn could be purified easily by chromatography to provide the first NHC metal complexes with six cyclohexyl or six cyclopentyl groups (Scheme 2). An NHC ligand with four cyclopentyl groups in the 2,6-positions, which is closely related to imidazolium salt 5a (which has six cyclopentyl groups in the 2,4,6-positions), was first mentioned by Organ et al, [18] but neither a synthetic protocol nor any characterization data were reported.…”

Selective Monoarylation of Primary Amines Using the Pd‐PEPPSI‐IPentCl Precatalyst

“…[15] To address this deficiency,w en ext examined the ability of phenolate derivatives to promote the selective formation of 8. Theuse of potassium chromanoxide (10), previously reported by us to affect the arylation of highly functionalized starting materials with the Pd-PEPPSI-IPent catalyst, [15a] resulted in complete conversion of 6 but with no selectivity for 8 (entry 6). However, the use of the isolated potassium salt of BHT [2,6-di-tert-butyl hydroxytoluene (11)] did show enhanced selectivity (7.4:1 8/9)w ith full conversion of the electrophile.U nfortunately,t here was only 63 %c onversion into 8 (entry 7).…”

“…[9] Despite these efforts,n os ingle universal catalyst, which is capable of promoting the amination of aryl and five-and six-membered heteroaryl halides using either simple or functionalized primary amines,h as been developed. We have previously reported that the Pd-PEPPSIIPent family [10] of palladium precatalysts has shown extremely high reactivity for the coupling of secondary alkyl amines [11] and primary and secondary anilines [12] with six-membered aryl and heteroaryl chlorides and bromides.H erein, we demonstrate the application of these catalysts in the selective amination of six-and five-membered (hetero)aryl chlorides and bromides using simple or functionalized primary aliphatic amines governed under one general protocol.…”