Ligand-Accelerated Cross-Coupling of C(sp2)–H Bonds with Arylboron Reagents

Keary M. Engle, Peter S. Thuy-Boun, Michael Dang, and Jin-Quan Yu

J. Am. Chem. Soc., 2011, 133, 18183–18193

DOI: 10.1021/ja203978r

A palladium catalyzed C–H functionalization between Molander's arylboronate reagents and phenylacetic acid derivatives was demonstrated. From extensive screening, this synthetic method was found to be efficacious utilizing Ac-Ile-OH as the ligand and Ag2CO3 as the oxidant. As a result, a high yielding and experimentally straightforward procedure has evolved into a useful cross-coupling protocol between arylacetic acid derivatives and aryltrifluoroborates.  The authors also found that this ligand accelertated process has superb functional group tolerance and may also be beneficial when applied to catalytic cross-coupling conditions under an oxygen atmosphere thus providing alternative "Green" conditions for this biaryl transformation.

A Highly Enantio- and Diastereoselective Molybdenum-Catalyzed Asymmetric Allylic Alkylation of Cyanoester

Conditions:
10 mol% Mo(CO)6, 15 mol% ligand, 10 mol% NaH, BSA, THF, 60 deg C
99% yield, 20/1 Branched/Linear, 11/1 dr, 97% ee

Barry M. Trost, John R. Miller, and Christopher M. Hoffman, Jr
J. Am. Chem. Soc., 2011, 133, 8165–8167

DOI: 10.1021/ja2029602

Summary: An efficacious Mo-catalyzed enantioselective allylation of various cyanoester nucleophiles provided a number of highly functionalized branched cyanoesters containing a quaternary carbon stereocenter.  This synthetic method generates the desired allylic cyanoesters products with high yield, chemoselectivity, diastereoselectivity and enantioselectivity.

Rhodium-Catalyzed Asymmetric Synthesis of 3,3-Disubstituted 1-Indanones

Ryo Shintani, Keishi Takatsu, Tamio Hayashi

Angewandte Chemie International Edition; 2006, 46, 3537-3737
DOI: 10.1002/anie.200700226

Summary: Chiral indanones that are difficult to obtain by other synthetic methods can be prepared via an enantioselective addition of aryl boronates to aryl alkynyl ketones. The resulting substituted indanones arrive from a tandem Rh-catalyzed C-H functionalization-cyclization sequence. This reaction utilizes a rhodium catalyst system with the asymmetric induction originating from a chiral bisphosphine ligand.

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%

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

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