Experimental and Computational Studies on Remote γ-C(sp³)–H Silylation and Germanylation of Aliphatic Carboxamides

Abstract

A Pd­(II)-catalyzed protocol for highly regioselective distal γ-C–H silylation and germanylation of aliphatic carboxylic acids is reported. Bidentate 8-aminoquinoline as the directing group was found to stabilize the six-membered palladacycle. A variety of aliphatic carboxylic acids and amino acids were silylated and germanylated in good yields and high diasteroselectivities. Detailed mechanistic studies involving isolation of a Pd­(II) intermediate, determination of the reaction rate and order, control experiments, and isotopic labeling and DFT studies were found to be crucial for elucidating the elementary steps involved in this distal aliphatic functionalization.

Directed C−H Bond Oxidation of Bridged Cycloalkanes Catalyzed by Palladium(II) Acetate

“…To summarize the mechanistic investigation we have proven that the catalytic cycle can be divided in two consecutive steps: reversible C−H activation to palladacycle C2 and irreversible oxidation to complex C4 , which proceeds with retention of configuration. The nature of the oxidation step is not yet proven,,, (two plausible pathways are proposed: concerted demetalation–oxidation or oxidation of Pd II complexes to Pd IV ) (Figure ).…”

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…Silylation of unactivated aliphatic chains, α-amino acid derivatives by means of Pd-catalysis at the β-position and even at the γ-one were studied by Zhang ( Scheme 84G ), 514 Shi ( Scheme 84H ) 515 and Maiti ( Scheme 84I ), 516 respectively. Albeit an excess of the coupling partners was generally necessary, with these three protocols functionalisation at the β- and even at the γ-position when the β-position was di-substituted was possible and extension to germanylation was even possible as depicted by Maiti.…”

Combining transition metals and transient directing groups for C–H functionalizations

“…at various positions (a, b, g and d) of different aliphatic systems. [16][17][18][19][20][21][22] Although enormous progress has been observed in DG assisted C-H bond activation, the major drawback of this approach is the installation of the DG in the substrate and also the removal at the end, and these oen demand tedious synthetic procedures. To resolve this problem, two alternative solutions have been applied: (i) use of a transient mediator 23 in a stoichiometric ratio and (ii) implementation of a traceless directing group.…”