Esters are valuable electrophiles for cross-coupling due to their ubiquity and ease of synthesis. However, harsh conditions are traditionally required for the effective cross-coupling of ester substrates. Utilizing a recently discovered precatalyst, Pd-catalyzed Suzuki-Miyaura and Buchwald-Hartwig reactions involving cleavage of the C(acyl)-O bond of aryl esters that proceed under mild conditions are reported. The Pd(II) precatalyst is highly active because it is reduced to the Pd(0) active species more rapidly than previous precatalysts.

Aryl carbonates, a common protecting group in synthetic organic chemistry, are potentially valuable electrophiles in cross-coupling reactions. Here, after performing a thorough evaluation of different precatalysts, we demonstrate that (dcypf)­Ni­(2-ethylphenyl)­(Br) (dcypf = 1,1-bis­(dicyclohexylphosphino)­ferrocene) is an efficient precatalyst for Suzuki–Miyaura reactions using a variety of aryl carbonates as substrates. Mechanistic studies indicate that (dcypf)­Ni­(2-ethylphenyl)­(Br), which contains a bidentate phosphine that binds in a trans geometry, is an effective precatalyst for these reactions for two reasons: (i) it rapidly forms the Ni(0) active species and (ii) it minimizes comproportionation reactions between the Ni(0) active species and both the unactivated Ni­(II) precatalyst and on-cycle Ni­(II) complexes to form catalytically inactive Ni­(I) species. In contrast, the state of the art precatalyst (dppf)­Ni­(o-tolyl)­(Cl) (dppf = 1,1-bis­(diphenylphosphino)­ferrocene), which contains a bidentate phosphine that binds in a cis geometry, forms Ni­(I) species during activation and is essentially inactive for aryl carbonate couplings. Although the exact reasons on a molecular level why the dcypf system is more active than the dppf system are unclear, our results indicate that in general Ni catalysts supported by the dcypf ligand will give better performance for catalytic reactions involving substrates which undergo relatively slow oxidative addition, such as aryl carbonates.

Transition metal-catalyzed transformations of amino acids and peptides could provide a powerful method for their site-selective modification. Here, we report non-decarbonylative Pd-catalyzed Suzuki-Miyaura reactions of phenyl ester derivatives of aspartic acid to form aryl-amino ketones. These products are potentially important in the synthesis of pharmaceuticals and our methodology represents a new route to access molecules of this type.

The synthesis of triarylmethanes via Pd-catalyzed Suzuki–Miyaura reactions between diarylmethyl 2,3,4,5,6-pentafluorobenzoates and aryl boronic acids is described. The system operates under mild conditions and has a broad substrate scope, including the coupling of diphenylmethanol derivatives that do not contain extended aromatic substituents. This is significant as these substrates, which result in the types of triarylmethane products that are prevalent in pharmaceuticals, have not previously been compatible with systems for diarylmethyl ester coupling. Furthermore, the reaction can be performed stereospecifically to generate stereoinverted products. On the basis of DFT calculations, it is proposed that the oxidative addition of the diarylmethyl 2,3,4,5,6-pentafluorobenzoate substrate occurs via an SN2 pathway, which results in the inverted products. Mechanistic studies indicate that oxidative addition of the diarylmethyl 2,3,4,5,6-pentafluorobenzoate substrates to (IPr)­Pd(0) results in the selective cleavage of the O–C­(benzyl) bond in part because of a stabilizing η3-interaction between the benzyl ligand and Pd. This is in contrast to previously described Pd-catalyzed Suzuki–Miyaura reactions involving phenyl esters, which involve selective cleavage of the C­(acyl)–O bond, because there is no stabilizing η3-interaction. It is anticipated that this fundamental knowledge will aid the development of new catalytic systems, which use esters as electrophiles in cross-coupling reactions.