Precise control of the site selectivity in ruthenium-catalyzed C–H bond amidations using cyclic amides as powerful directing groups

Abstract

Selective C-H functionalizations aiming at the formation of new C-N bonds is of paramount importance in the context of step- and atom-economy methodologies in organic synthesis. Although the implementation of...

DLPNO-CCSD(T) and DFT study of the acetate-assisted C–H activation of benzaldimine at [RuCl2(p-cymene)]2: the relevance of ligand exchange processes at ruthenium(ii) complexes in polar protic media

“…In particular, PCM and SMD solvation models have been successfully employed to investigate many ruthenium( ii )-catalyzed C–H activation and functionalization processes in almost all kinds of solvents (as 2-MeTHF, dioxane, toluene, DCE, acetonitrile, MeOH, TFE, tert -butanol, HFIP, or AcOH). 12–33 Nevertheless, the suitability of implicit solvent models for the study of ionic reactions that are performed in protic solvents is still controversial, as strong, specific, solvent–solute H-bonding interactions are seemingly ignored. These kinds of directed interactions are not captured by the CPCM and SMD models and this deficiency could compromise the accuracy of our results.…”

“…Most of the current knowledge of the mechanism of carboxylate-assisted C–H activations by ruthenium( ii ) complexes is based on computational evidence. 17 DFT studies covering the reactions of phenylpyrazoles, 18 benzylamines, 19 phenylpyridines, 20 N -aryl-oxazolidinones, 21 naphthols, 22 aryl carboxylic acids, 23 arylphosphonates, 24 arylacetamides, 16 d ,25 benzamides, 26 pyridylindoles, 27 phenylketones, 28 hydroxy-chromones 29 or phenylimidazoles 30 promoted by [RuCl 2 ( p -cymene)] 2 and acetate anions (or preformed Ru(OAc) 2 ( p -cymene)) support initial substrate ( A ) binding to the ruthenium precursor ( B ) followed by dissociation of a ligand (from C ) and creation of a key intermediate with a vacant site at which the M–C bond can form (see Scheme 2). Most of these electrophilic intermediates are cationic in nature ( D + ) 31 but alternative routes involving neutral intermediates equipped with two acetate ligands bound to the ruthenium ( F L ) and showing η 6 – η 2 slippage 32 or substitution of the arene co-ligand by solvent or a second substrate molecule 33 have been also reported.…”

Access to Amides and Lactams via Pyridotriazole as a Transformable Directing Group

“…Amide and lactam scaffolds are a class of substantial motifs frequently found in pharmaceuticals and naturally occurring molecules like imatinib, lenalidomide, and elmenol H. − A wide range of approaches to constructing such indispensable amide bonds have been developed, ranging from conventional acylation of amines mediated by amide coupling agents , to modern strategies such as catalytic direct amidation , or visible light irradiation. , Among these studies, transition-metal-catalyzed C–H activation stands out as a simpler synthetic route for direct amidation of unactivated C–H bonds. − Many transition-metal-catalyzed C–H functionalization methods require directing groups (DGs), − especially transformable DGs, to enhance the regioselectivity and practicality. − By the DG-assisted C–H activation strategy, selectively installing nitrogen-based functional groups (FGs) into molecules via the direct addition of C–H bonds to unsaturated polar C–N π-bonds represents the most powerful and economical method for rapid amide and lactam synthesis. − We envisioned isocyanates to be particularly useful. As useful carbon synthons in organic synthesis, isocyanates have been extensively implemented in the construction of C–C bond formation for forging amides. − Hence, employing isocyanates as FGs would be a more straightforward approach to the synthesis of amides.…”