ADVERTISEMENT

An Application Of Rhodium Catalyst In Directed C-H Functionalization Of Quinoline N-Oxides

Over the past few decades, transition-metal-catalyzed C−H functionalization has emerged as a powerful strategy to synthesize complex molecules. The development of direct methods for activating the inactive C-H bonds to generate C-C bonds is more attractive but challenging due to the higher bond dissociation energy (BDE). Nevertheless, how to control the regioselectivity if the substrates have more than one reacting C−H bond remains a challenge. Therefore, the chelation-assisted transformation has become a common and powerful method for the regioselective functionalization of C–H bonds.

Quinoline is an important molecular skeleton in the medical industry, especially in many drugs and biologically active molecules. Accordingly, the development of efficient methods to produce substituted quinoline is of great significance. Recently, much effort has been made in the area of C−H functionalization of quinoline at different positions. N-oxide as a directing group has attracted significant attention, which has been used to achieve the desired regioselective control.

ADVERTISEMENT

A significant number of methods exist for transition-metal-catalyzed functionalization at the C-2 position of quinoline N-oxides. By contrast, only a few examples have been reported for the selective C-8 functionalization of quinoline N-oxides. Organoboron reagents, especially alkyl boron reagents, have been used extensively in C−H functionalization.

Our research group (Prof. Liu’s group, SIMM, Shanghai, China) has focused on C-H bond functionalization. In a recent study, we have developed Rhodium(III)-catalyzed site-selective C–H alkylation and arylation of pyridones using organoboron reagents. Inspired by the previous work, we disclose a Rh(III)-catalyzed C-8 methylation and arylation of quinoline N-oxides with potassium trifluoroborate reagents.

After extensive optimization, the standard conditions for the Rh-catalyzed C-H functionalization reaction are: 5 mol% [RhCp*Cl2]2, 20 mol% AgSbF6, 2 equiv of AgOAc, and 2 equiv of MeBF3K in DME at 65 °C for 18 h under argon. C-8 methylated and arylated quinolines have been synthesized at good yields with the optimal reaction conditions. This finding has been utilized for the synthesis of selective agrochemical fungicide quinoxyfen derivatives.

The mechanism was proposed based on preliminary mechanistic experiments. The rhodacycle has been synthesized, isolated and characterized. The reaction could also proceed well with the synthesized rhodacycle, illustrating that this rhodacycle should be the active intermediate species in the catalytic cycle.

ADVERTISEMENT

In summary, we developed a simple, highly efficient Rh(III)-catalyzed direct site-selective methylation and arylation of quinoline N-oxides at the C-8 Position using potassium trifluoroborates under mild conditions. This concise protocol and further chemical transformations of the products might have important applications in the synthesis of biologically active compounds.

This study, Cp*Rh(III)-Catalyzed Directed C-H Methylation and Arylation of Quinoline N-Oxides at the C-8 Position was recently published in the journal Advanced Synthesis & Catalysis.

Comments

READ THIS NEXT

Potential Probing Techniques For Future Energy Supply System-Solid Oxide Fuel Cells (SOFCs)

Currently, a brand new worldwide consensus is gradually forming: hydrogen energy acts as an interactive link among a variety of […]

A Novel Method For Fluoride Detection

Paracelsus’ old adage “the dose makes the poison” is well exemplified by fluoride. Many people know that fluoride is commonly […]

Searching For Life: Methane May Hold Answers To Life On Mars & The Universe

The search for life in the universe has far-reaching effects, as it would bring into question our place as humans […]

Are We At A Tipping Point For Climate Change?

In a new study published in the Proceedings for the National Academy of Sciences, climatologist Will Steffen from Australian National […]

Baby Rattlesnake

A baby rattlesnake typically has similar markings to an adult rattlesnake but are overall darker in appearance and lack the […]

Aluminum Ion Batteries For High-Demand Applications

Aluminum ion batteries are being developed to meet high demand applications, such as electrically-powered vehicles for private, public, and commercial […]

Eating Extra Virgin Olive Oil Found To Lower Risk Of Alzheimer’s Disease

The Mediterranean diet is ranked as one of the most healthful diets on the planet. It incorporates different foods which […]

Science Trends is a popular source of science news and education around the world. We cover everything from solar power cell technology to climate change to cancer research. We help hundreds of thousands of people every month learn about the world we live in and the latest scientific breakthroughs. Want to know more?