817556-88-0Relevant articles and documents
Cyclometalated Ruthenium Catalyst Enables Ortho-Selective C–H Alkylation with Secondary Alkyl Bromides
Wang, Gang-Wei,Wheatley, Matthew,Simonetti, Marco,Cannas, Diego M.,Larrosa, Igor
supporting information, p. 1459 - 1468 (2020/05/25)
Although Ru-catalyzed meta-selective sp2 C–H alkylation with secondary alkyl halides is well established, ortho selectivity has never been achieved. We demonstrate that the use of a cyclometalated Ru-complex, RuBnN, as the catalyst results in a complete switch of the inherent meta-selectivity to ortho selectivity in the Ru-catalyzed sp2 C–H alkylation reaction with unactivated secondary alkyl halides. The high catalytic activity of RuBnN allows mild reaction conditions that result in a transformation of broad scope and versatility. Preliminary mechanistic studies suggest that a bis-cycloruthenated species is the key intermediate undergoing oxidative addition with the alkyl bromides, thus avoiding the more common SET pathway associated with meta-selectivity. Direct C–H functionalization is a powerful tool for milder and more environmentally friendly syntheses of biologically active compounds, as well as offering easy access to unexplored chemical space in drug discovery. However, major challenges remain for these methods to be widely applicable. The development of new catalysts with diverse and superior reactivity is key to address these challenges. Here, we show for the first time that cyclometalated Ru-complexes are able to catalyze the directed ortho-C–H alkylation of arenes with secondary alkyl bromides, enabling the late-stage functionalization and diversification of pharmaceuticals. The obtained regioselectivity is in stark contrast to that delivered by the commonly used arene-bound Ru-complexes, which afford exclusive meta-alkylation. Our work points a way to further rationally design next-generation Ru-catalysts with improved control over selectivity and reactivity, and a richer synthetic toolbox for chemists in the future. Here, we report the first ortho-selective sp2 C–H bond alkylation with secondary alkyl bromides in the Ru catalytic platform, enabled by cyclometalated ruthenium(II) complex RuBnN. Mechanistic studies indicate that the formation of a bis-cycloruthenated intermediate enables an oxidative addition to occur, thus avoiding the single-electron transfer (SET) pathway associated with meta-selectivity in other Ru catalytic systems. The reaction is tolerant of a variety of medicinally relevant functional groups and has been used to modify existing pharmaceuticals.
Cobalt-catalyzed chelation-assisted alkylation of arenes with primary and secondary alkyl halides
Gao, Ke,Yamakawa, Takeshi,Yoshikai, Naohiko
, p. 2024 - 2039 (2014/08/05)
Cobalt-N-heterocyclic carbene catalytic systems have been developed for chelation-assisted ortho-alkylation of aromatic compounds with alkyl halides. Aryl imines can be selectively monoalkylated at room temperature by various primary or secondary alkyl chlorides or bromides. The catalytic system can also be applied to 2-arylpyridine derivatives, which in the absence of steric hindrance are amenable to dialkylation by an excess of the alkyl halide. Mechanistic experiments, including reactions of stereochemical probes and radical clocks, indicate that the reaction involves single-electron transfer from the cobalt center to the alkyl halide to form the corresponding alkyl radical, which has a finite lifetime before it undergoes C-C bond formation. Georg Thieme Verlag Stuttgart, New York.
Ruthenium-catalyzed para-selective oxidative cross-coupling of arenes and cycloalkanes
Guo, Xiangyu,Li, Chao-Jun
supporting information; experimental part, p. 4977 - 4979 (2011/11/12)
A novel, direct para-selective oxidative cross-coupling of benzene derivatives with cycloalkanes catalyzed by ruthenium was developed. A wide range of arenes bearing electron-withdrawing substituents was functionalized directly with simple cycloalkanes with high para-selectivity; arenes with electron-donating groups were mainly para-functionalized. Benzoic acid can be used directly.
