Gabriela A. Grasa

Catalytic cross-coupling reactions mediated by palladium/nucleophilic carbene systems

Abstract In this mini-review, we present a summary of our recent work in the field of palladium-catalyzed cross-coupling reactions, with emphasis on the use of nucleophilic N-heterocyclic carbenes (NHC) as ancillary ligand. The palladium-mediated coupling reactions investigated include the Suzuki–Miyaura, Kumada–Tamao–Corriu, Heck, Sonogashira, Stille, Hiyama and aryl amination reactions.

Catalytic activity of Pd(II) and Pd(II)/DAB-R systems for the Heck arylation of olefins

Abstract Palladium-catalyzed reactions of aryl bromides with various olefins involving Pd(II)/diazabutadiene (DAB-R) systems have been investigated. The scope of a coupling process using Pd(II) sources and an α-diimine as ligand in the presence of Cs2CO3 as base was tested using various substrates. The Pd(OAc)2/DAB-Cy (1, DAB-Cy=1,4-dicyclohexyl-diazabutadiene) system presents the highest activity with respect to electron-neutral and electron-deficient aryl bromides in coupling with electron rich olefins. The synthesis and X-ray characterization of a Pd(II)-diazabutadiene ligand is reported. Extensive optimization experiments showed that another Pd(II) source, Pd(acac)2 (acac=acetylacetonate), proved to activate aryl bromides at high temperatures, low catalyst loadings when the appropriate concentration of nBu4NBr additive was employed. The effect of the DAB-Cy ligand is important at very low catalyst loadings and high temperatures. Pd(acac)2 and Pd(acac)2/DAB-Cy precatalysts were very effective for the arylation of various olefins with aryl bromides with respect to reaction rate, catalyst loadings, and functional group tolerance.

Synthesis and X-ray structure determination of highly active Pd(II), Pd(I), and Pd(0) complexes of di(tert-butyl)neopentylphosphine (DTBNpP) in the arylation of amines and ketones.

The air-stable complex Pd(η(3)-allyl)(DTBNpP)Cl (DTBNpP = di(tert-butyl)neopentylphosphine) serves as a highly efficient precatalyst for the arylation of amines and enolates using aryl bromides and chlorides under mild conditions with yields ranging from 74% to 98%. Amination reactions of aryl bromides were carried out using 1-2 mol % Pd(η(3)-allyl)(DTBNpP)Cl at 23-50 °C without the need to exclude oxygen or moisture. The C-N coupling of the aryl chlorides occurred at relatively lower temperature (80-100 °C) and catalyst loading (1 mol %) using the Pd(η(3)-allyl)(DTBNpP)Cl precatalyst than the catalyst generated in situ from DTBNpP and Pd(2)(dba)(3) (100-140 °C, 2-5 mol % Pd). Other Pd(DTBNpP)(2)-based complexes, (Pd(DTBNpP)(2) and Pd(DTBNpP)(2)Cl(2)) were ineffective precatalysts under identical conditions for the amination reactions. Both Pd(DTBNpP)(2) and Pd(DTBNpP)(2)Cl(2) precatalysts gave nearly quantitative conversions to the product in the α-arylation of propiophenone with p-chlorotoluene and p-bromoanisole at a substrate/catalyst loading of 100/1. At lower substrate/catalyst loading (1000/1), the conversions were lower but comparable to that of Pd(t-Bu(3)P)(2). In many cases, the tri-tert-butylphosphine (TTBP) based Pd(I) dimer, [Pd(μ-Br)(TTBP)](2), stood out to be the most reactive catalyst under identical conditions for the enolate arylation. Interestingly, the air-stable Pd(I) dimer, Pd(2)(DTBNpP)(2)(μ-Cl)(μ-allyl), was less active in comparison to [Pd(μ-Br)(TTBP)](2) and Pd(η(3)-allyl)(DTBNpP)Cl. The X-ray crystal structures of Pd(η(3)-allyl)(DTBNpP)Cl, Pd(DTBNpP)(2)Cl(2), Pd(DTBNpP)(2), and Pd(2)(DTBNpP)(2)(μ-Cl)(μ-allyl) are reported in this paper along with initial studies on the catalyst activation of the Pd(η(3)-allyl)(DTBNpP)Cl precatalyst.

Structural characterization and catalytic activity of the rhodium–carbene complex Rh(PPh3)2(IMes)Cl (IMes=bis(1,3-(2,4,6-trimethylphenyl)imidazol-2-ylidene)

Abstract The rhodium–carbene complex Rh(PPh3)2(IMes)Cl (2) is an active catalyst for the hydroboration of simple olefins at room temperature. The reactivity of 2 was also tested in the methylenation of aldehydes. The crystal structure of 2 is also reported.

A Highly Efficient, Practical, and General Route for the Synthesis of (R3P)2Pd(0): Structural Evidence on the Reduction Mechanism of Pd(II) to Pd(0)

A highly efficient, practical, and general method was developed to synthesize a family of (R(3)P)(2)Pd(0) complexes, using a stoichiometric amount of phosphine ligands and readily available Pd(II) precursors. The stepwise pathway of reducing Pd(II) to Pd(0) was established by isolating two key intermediates. Both [t-Bu(2)(4-Me(2)NC(6)H(4))P](2)Pd and (t-Bu(2)NpP)(2)Pd are new compounds. Preliminary studies on [t-Bu(2)(4-Me(2)NC(6)H(4))P](2)Pd have indicated that it is a very active catalyst (84-95% isolated yield) in the Cu-free Sonogashira coupling involving aryl and heteroaryl chlorides at 0.5 mol % catalyst loading.

Synthesis of a hyaluronan neoglycopolymer by ring-opening metathesis polymerization.

A hyaluronan (HA)-derived disaccharide was synthesized bearing an n-pentenyl spacer arm, which facilitated disaccharide derivatization with a norbornene template. Subsequent ring opening metathesis polymerization of the monomer produced an HA-mimetic neoglycopolymer of low polydispersity.