Ru₃(CO)₁₂-Catalyzed Coupling Reaction of sp³C−H Bonds Adjacent to a Nitrogen Atom in Alkylamines with Alkenes

Abstract

Catalytic reactions which involve the cleavage of an sp(3) C-H bond adjacent to a nitrogen atom in N-2-pyridynyl alkylamines are described. The use of Ru(3)(CO)(12) as the catalyst results in the addition of the sp(3) C-H bond across the alkene bond to give the coupling products. A variety of alkenes, including terminal, internal, and cyclic alkenes, can be used for the coupling reaction. The presence of directing groups, such as pyridine, pyrimidine, and an oxazoline ring, on the nitrogen of the amine is critical for a successful reaction. This result indicates the importance of the coordination of the nitrogen atom to the ruthenium catalyst. In addition, the nature of the substituents on the pyridine ring has a significant effect on the efficiency of the reaction. Thus, the substitution of an electron-withdrawing group on the pyridine ring as well as a substitution adjacent to the sp(2) nitrogen in the pyridine ring dramatically retards the reaction. Cyclic amines are more reactive than acyclic ones. The choice of solvent is also very important. Of the solvents examined, 2-propanol is the solvent of choice.

Cu-catalyzed cross-dehydrogenative coupling: A versatile strategy for C–C bond formations via the oxidative activation of sp 3 C–H bonds

“…The syntheses of these compounds have attracted much attention in industrial and academic research because of their biological and pharmaceutical properties. Recently, some excellent examples based on the direct sp 3 C-H bond activation adjacent to a nitrogen atom for C-C bond formations were reported by Murahashi et al (7), Murai and coworkers (8)(9)(10)(11), Ishii and coworkers (12), Sames and coworkers (13)(14)(15), Davies et al (16,17), Yoshimitsu et al (18), Yoshida and coworkers (19)(20)(21)(22), and Yi and coworkers (23). Although these are elegant methodologies, most of them required another functionalized substrate.…”

Ruthenium-Catalyzed Transfer Hydrogenation for C–C Bond Formation: Hydrohydroxyalkylation and Hydroaminoalkylation via Reactant Redox Pairs

“…[92][93][94] Indeed, with the exception of the present authors work, [95][96][97][98][99] all other late transition metal catalyzed hydroaminoalkylations require pyridyl directing groups in combination with mono-olefin reactants. [100][101][102][103][104][105][106][107][108] In a significant departure from prior art, it was found that ruthenium catalyzed hydrogen transfer from 4-aminobutanol to 1-substituted-1,3-dienes results in the generation of dihydropyrrole-allylruthenium pairs, which combine to form products of hydroaminoalkylation with good to complete control of anti-diastereoselectivity (Scheme 18). 95 As corroborated by deuterium labeling experiments, kinetically preferred hydrometalation of the terminal olefin of the 1-substituted-1,3-diene delivers a 1,1-disubstituted π-allylruthenium complex that isomerizes to the more stable monosubstituted π-allylruthenium complex.…”

Cα–H Oxidations of Amines to Amides: Expanding Mechanistic Understanding and Amine Scope through Catalyst Development

“…Path B would result in the formation of an iminium intermediate, which in turn would react with H 2 O as nucleophile. In path A, 18 O incorporation could occur if the putative iron-oxo intermediate attacking the C α -H bond is formed through reaction with H 2 O or if exchange between the oxo ligand and external H 2 O is possible. As such pathways have been documented in previous studies, 17 both pathways A and B are possible for the discussed amine oxidation.…”

“…Indeed, several methodologies in the literature are known that realize such amine C α -H functionalizations to form new C α -alkyl, 18,19 C α -alkynyl, 20 C α -Ar, 21 C α -Ac, 22 and C α -CN 23 bonds.…”