[reaction: see text] The palladium-catalyzed coupling reaction of 2-pyridyl esters with organoboron compounds is described. The reaction is compatible with various functional groups and proceeds under mild reaction conditions. The coordination of the nitrogen atom to Pd is a key step for efficient reaction.

The ruthenium-catalyzed carbonylation at the C-H bond of five-membered N-heteroaromatic compounds is described. The reaction of imidazoles with CO and olefins in toluene in the presence of a catalytic amount of Ru(3)(CO)(12) results in carbonylation of the C-H bond at the 4-position (adjacent to the sp(2)-nitrogen) of the imidazole ring to give acylated imidazoles in good to high yields. A wide range of olefins can be utilized in the carbonylation reaction, and a variety of functional groups are compatible under the reaction conditions. Other five-membered N-heteroaromatic compounds, such as pyrazoles, oxazoles, and thiazoles, can also be used for the carbonylation reaction, and in all cases, carbonylation takes place exclusively at a C-H bond alpha to the sp(2) nitrogen. The reactivity of the five-membered heterocycles corresponds to the pK(a) of the conjugate acid of these heterocycles. The higher the pK(a) of the substrate, the higher is the reactivity. This indicates that the pK(a) values are related to the ability of the nitrogen atom in the substrates to coordinate to a ruthenium center. The coordination of the substrates to the ruthenium center in the catalyst complex is a necessary prerequisite for the carbonylation to proceed.

Rhodium catalyzed conjugate addition of an aryl boronic acid to α-methylamino acrylates followed by enantioselective protonation of the oxa-π-allylrhodium intermediate provides access to aryl substituted β 2 -amino acids. The impact of the different variables of the reaction on the levels of enantioselectivity has been assessed.Rhodium catalyzed conjugate addition of organoboron, 1 organosilicon, 2 and organotin 3 reagents to α,β-unsaturated systems has seen tremendous advances in the past decade. Hayashi, Miyaura and others have developed highly efficient enantioselective protocols for these conjugate additions that allows for the establishment of a new chiral center at the β-carbon. 4 In contrast, use of this strategy to establish a stereocenter at the α-carbon has met with limited success. 5 Recently several examples of enantioselective rhodium enolate protonations leading to enantioenriched α-amino acids and succinates have been reported. 6Development of new methods for the synthesis of β-amino acids is important. 7 There are a number of enantioselective methods for the synthesis of β-substituted-β-amino acids (β 3 -amino acids). 8 In contrast, there are few methods for the synthesis of α-substituted-β-amino acids (β 2 -amino acids) enantioselectively. 7 This substitution pattern is of interest since it is present in naturally occurring amino acids as well as compounds with potential therapeutic value. 9We have recently developed a novel method for the synthesis of β 2 -amino acids using free radical chemistry. 10 The stereochemistry in these reactions was established by an enantioselective H-atom transfer after conjugate radical addition. 11 One deficiency of the Hatom transfer methodology was the inability to incorporate aromatic groups into the targets. We surmised that a rhodium catalyzed conjugate addition of an aryl boronic acid to 1 followed by enantioselective protonation of the oxa-π-allylrhodium intermediate 2 1 could provide access to aryl substituted β 2 -amino acids (Scheme 1). 12 Recently Frost and co-workers have reported a racemic version of the transformation shown in Scheme 1. 13 In this work we have evaluated several variables for the conversion of 1 to 3 including the nature of the proton source, chiral ligand, catalyst, nitrogen protecting group, and the ester substituent and report a reasonably efficient method for the synthesis of enantioenriched β 2 -amino acids.Our work began with the identification of an optimal rhodium catalyst for the addition of phenylboronic acid to compound 5a using BINAP as the chiral ligand and water as the proton source. Our initial choice of catalyst, ligand, and proton source was based on the work of Hayashi, 14 Genet, 6a Reetz, 6b and Frost. 6c Results from these experiments are presented in Table 1. The catalyst rhodium (acac)bisethylene complex gave good yield of the addition product with modest enantioselectivity (entry 1). The reactions were effective at 50 °C.Mukund.Sibi@ndsu.edu.

The Ru3(CO)12-catalyed cross-coupling reaction of esters with organoboron compounds leading to ketones is described. A wide variety of functional groups can be tolerated under the reaction conditions. Aromatic boronates function as a coupling partner to give aryl ketones. Acyl-alkyl coupling to dialkyl ketones is also achieved by the use of 9-alkyl-9-BBN in place of boronates. The Ru3(CO)12-catalyzed decarbonylative reduction of esters with ammonium formate (HCOONH4) leading to hydrocarbons is also described. No expected aldehydes are produced, and controlled experiments indicate that aldehydes are not intermediate for the transformation. A hydrosilane can also be used as a reducing reagent in place of HCOONH4. A wide variety of functional groups are compatible for both reactions. The key step for both catalytic reactions is the directing group-promoted cleavage of an acyl carbon-oxygen bond in esters, leading to the generation of acyl transition metal alkoxo complexes.

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