Highly Selective Intramolecular Carbene Insertion into Primary C–H Bond of α-Diazoacetamides Mediated by a (p-Cymene)ruthenium(II) Carboxylate Complex

Abstract

Complex [(p-cymene)Ru(η(1)-O(2)CCF(3))(2)(OH(2))] mediated transformation of α-diazoacetamides ArCH(2)N(C(CH(3))(3))C(O)CHN(2) to result in carbene insertion into the primary C-H bond exclusively, with the γ-lactam products being isolated in up to 98% yield. This unexpected reaction is striking in view of the presence of usually more reactive sites such as secondary C-H bonds in the substrates. DFT calculations based on proposed Ru-carbene species provide insight into this unique selectivity.

Palladium Catalysis in the Intramolecular Carbene C–H Insertion of α‐Diazo‐α‐(methoxycarbonyl)acetamides to Form β‐Lactams

“…The competition between Csp 3 –H insertion leading to β‐lactams and intramolecular aromatic cycloaddition to give the corresponding cycloheptapyrrolone is also common in reactions of α‐diazoacetamides catalyzed by Rh II[11a] and Ru II catalysts. [11b], According to previous mechanistic studies on related Rh II ‐catalyzed transformations, the competitive formation of β‐lactams and aromatic ring reaction products is probably due to the stereoelectronic competition between the two conformational isomers of the metallacarbene undergoing the intramolecular reactions . A strategy to improve site‐selectivity in the transition‐metal‐catalyzed carbene reactions of α‐diazoacetamides involves replacing one of the N ‐substituents at the amide moiety with a bulky group, which sterically biases the conformational preference around the amide N–C(O) bond and makes the metallacarbene reaction at the remaining substituent more feasible.…”

Homologation Reaction of Ketones with Diazo Compounds

“…Due to the very reactive nature of the carbene species in most of these processes, transition metals able to stabilize the carbene are often employed. Despite the seminal reports on the use of copper as catalysts in the decomposition of diazo compounds more than 100 years ago, dirhodium carbenoids were reported in the 1970s as viable alternatives , to the more reactive copper carbenoids and they have been extensively investigated. ,,− Other metal complexes including palladium, , iridium, − cobalt, iron, ,− and ruthenium − centers have also been successfully reported to moderate the reactivity of the carbene moiety.…”

Reactivity and Selectivity in Catalytic Reactions of Enoldiazoacetamides. Assessment of Metal Carbenes as Intermediates

“…Strain energy inhibits the C–H insertion process, whereas dearomatization is a barrier for aromatic cycloaddition. The competition between C–H insertion and aromatic cycloaddition is common in reactions of diazoamides catalyzed by dirhodium­(II) compounds and has also been described for those catalyzed by a ruthenium porphyrin catalyst, but reactions with other catalysts whose results are documented in Table have not previously received attention. As has been previously reported, however, the 3 : 4 ratio is dependent on catalyst ligands.…”