C-C Bond Activation with Selective Functionalization: Preparation of Unsymmetrical Biaryls from Benzonitriles

Joseph A. Miller
Tetrahedron Letters; 2001, 42, 6991–6993
DOI:10.1016/S0040-4039(01)01476-9

Summary: Nickel catalysts have been known to coordinate and subsequently activate the C-CN bond of nitrile compounds. However, a practical procedure to perform a cross-coupling reaction with these substrates and an appropriate organometallic was unknown until the present work. Thus, reaction of a benzonitrile with an aryl Grignard derivative in the presence of a Ni catalyst, such as [NiCl2(PMe3)2], provides the corresponding unsymmetrical biaryl in high yield and with high selectivity. Ligand screening found that trimethylphosphine was the most effective ligand. The Grignard reagent was modified (for example, ArMgOt-Bu) to reduce the amount of direct addition of the organomagnesium reagent to the nitrile. This group has also expanded the methodology to alkyl, alkenyl, and alkynyl organometallics.

16 examples, 69-97% yield
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Rhodium-Catalyzed Arylative and Alkenylative Cyclization of 1,5-Enynes Induced by Geminal Carbometalation of Alkynes

Yiyun Chen and Chulbom Lee
J. Am. Chem. Soc., 2006, 128, 15598 -15599
DOI: 10.1021/ja067125+

Summary: A Rh(I)-catalyzed alkyne-boronic acid addition-cyclization has been developed to afford various alkenyl ketone derivatives. The reaction is believed to proceed through a metal vinylidene complex which eventually undergoes an intramolecular conjugate addition to provide the desired cyclized ketone adduct.

10 examples : Reaction Optimization (0-65% yield)
19 examples: Reaction Scope (11-84% yield)
2 examples: Deuterated substrates for mechanistic studies

Gold(I)-Catalyzed Intramolecular Hydroamination of Alkenyl Carbamates

Xiaoqing Han, Ross A. Widenhoefer
Angewandte Chemie International Edition; 2006, 45, 1747-1749
DOI: 10.1002/anie.200600052

Summary: This paper describes the intramolecular gold(I)-catalyzed hydroamination of olefinic carbamates for the preparation of functionalized saturated nitrogen heterocycles. The products incorporate either five or six membered ring system via an exo-trig cyclization. This Au(I)-catalyzed reaction overcomes several limitations of the corresponding Pt-mediated annulation such as substrate scope and reaction temperature. Determination of the optimized conditions (ligand and solvent studies - 8 examples: 7-98% yield) plus 15 additional examples using the optimized conditions: 59-97% yield

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