Palladium-Catalyzed Benzene Arylation: Incorporation of Catalytic Pivalic Acid as a Proton Shuttle and a Key Element in Catalyst Design

Marc Lafrance and Keith Fagnou

J. Am. Chem. Soc., 2006, 128, 16496 -16497

DOI: 10.1021/ja067144j

Summary: C-H activation processes represent an important area of synthetic exploration since the starting materials required are less functionalized and potentially less expensive. A Pd-pivalic acid co-catalyst system has been utilized in the direct arylation of benzene and aryl bromides. Experimental and computational studies indicate that the pivalate anion is a key component in the palladation/C-H bond breaking event. Additionally, aryl chorides and iodides were found to be poor substrates.

8 examples: 55-85%

Palladium-Catalyzed Kumada-Corriu Cross-Coupling Reactions at Low Temperatures Allow the Use of Knochel-type Grignard Reagents

Ruben Martin and Stephen L. Buchwald
J. Am. Chem. Soc.; 2007, 129, 3844 - 3845.
DOI: 10.1021/ja070830d 
Summary: Biaryl compounds are important structural elements in natural products and medicinally useful drug substances. This paper reports a useful advance in the palladium-catalyzed Kumada-Corriu biaryl cross-coupling reaction. The significance of this work is derived from the ability to conduct the reactions at low temperature (-20 to -65 deg C). This was made possible by (i) the application of Knochel's methodology, to form the desired Grignard reagents, containing in many cases reactive functional groups on the aromatic ring and (ii) the proper choice of biaryl phosphine ligand. Martin and Buchwald were able to take advantage of this chemistry and and prepare a variety of biaryl compounds including heterocyclic and polyfluoro biaryls. Screening of aryl iodides and triflates with various ligands revealed that superior conditions utilized aromatic iodides in conjunction with either DavePhos or S-Phos. Nitriles, esters, acetals, and amines are compatible under these conditions.

21 examples: 55-96% yield