ADVERTISEMENT

Palladium-catalyzed Deoxygenative Amination Of Phenols

Arylamines serve as important structural units in pharmaceuticals, pigments and functional materials. They are also versatile intermediates in numerous transformations such as C-halo (the Sandmeyer and Schiemann reactions) or C-N (the Buchwald-Hartwig, the Chan-Lam, and the Ullmann reactions) bond formations.

Very recently, N-cyclohexyl anilines have been used as a ligand to promote dehydrogenative transformations, and as an antioxidant in food chemistry. To date, a series of elegant methods for the synthesis of N-cyclohexyl anilines have been developed, which can be divided into two categories: one involves the use of anilines as amino source, with coupling partners including arylboronic acids, phenols, anilines, cyclohexanones or cyclohexanols; and the other relates to the use of cyclohexylamines as precursors, with coupling partners covering various aryl sources such as haloarenes, phenol and its derivatives, arylboronic acids, and aryl Grignard reagents.

ADVERTISEMENT

However, most of these methods require the prefunctionalization, thereby decreasing the total reaction efficiency. Phenols are abundant and naturally occurring motifs in renewable lignocellulosic biomass and are important precursors of aryl or cyclohexyl groups. In 2015, our group developed a Pd-catalyzed reductive coupling of phenols with amines using sodium formate as a convenient hydrogen source to produce anilines or cyclohexylamines. Later, Taddei accomplished this transformation in a flow reactor.

In 2016, Beller reported a Pd-catalyzed deoxygenative coupling of phenols or aryl ethers to generate alkylated cyclohexylamines with Lewis acid Hf(OTf)4 as co-catalyst under molecular H2, and Fu’s group further investigated N-cyclohexylation of amines with phenols using Al2O3 supported palladium hydride (PdHx) catalyst.

The N-N bond cleavage of hydrazines has recently been utilized as a strategy for the formation of C-N bond through the transition-metal-catalyzed C-H bond functionalization. Indeed, it has earlier been documented that hydrazines served as a nitrogen source with carbonyl compounds to prepare amines via catalytically hydrogenative N-N cleavage. Yet to our knowledge, there seems to be no report regarding the synthesis of amines from phenols with hydrazine via the cleavage of C-O and N-N bonds.

In 2015, our group also reported a formal coupling of phenol with amines catalyzed by palladium to generate aniline products. In this paper, we present an efficient palladium-catalyzed direct deoxygenative coupling of phenols with hydrazine or hydroxylamine as nitrogen atom source via C-O bond and N-N/O bond cleavages, which can not only greatly improve the efficiency to synthesize the N-cyclohexyl aniline type substrates but also utilize biomass-derived phenols and common industrial starting materials or catalyst (hydrazine, hydroxyamine, Pd/C, sodium formate).

ADVERTISEMENT

For the scope of such a transformation, generally speaking, less hindered C-alkylated phenols such as cresols, the hydroxyl benzoates and hydroxyphenyl acetates and the aryl ethers which are more abundant structural units in biomass resources, for example, lignins, all proceeded smoothly under the standard conditions.

Mechanism studies suggest that this chemistry probably involves the sequential formations of various intermediates cyclohexanone or cyclohexanone, hydrazone or azine, and cyclohexylamine. This chemistry involves a complex sp2 C-O bond and N-N or N-O bond-cleavage process and enables access to a variety of N-substituted cyclohexyl anilines from lignin-derived phenols. Further deoxygenative transformations of biomass are underway in our lab.

This study, Palladium-Catalyzed Synthesis of N-Cyclohexyl Anilines from Phenols with Hydrazine or Hydroxylamine via N-N/O Cleavage was recently published by Jiang-Sheng Li, Zihang Qiu and Chao-Jun Li in the journal Advanced Synthesis & Catalysis.

Comments

READ THIS NEXT

10 Examples Of Proteins: In Food And Biology

Proteins are a type of biological molecule that is composed primarily out of amino acids. Proteins perform a vast array […]

Is A Drone With A Thermal Camera As Good At Locating Grassland Songbird Nests As Traditional Search Methods?

As captured in the phrase, “the canary in the coal mine,” songbirds are known to be indicators of ecosystem health. […]

Using Behavioral Treatment To Curb Conduct Problems In Children With Callous-Unemotional Traits

Behavior problems in children take many forms, including verbal defiance towards authority figures, non-compliance, and physical aggression – all of […]

Microplastics In The Environment Help Spread Antibiotic Resistance And Change Microbial Interactions

Plastics are low-cost, durable, and versatile materials used in the manufacture of many things we use for daily life, e.g., […]

What Is Federalism?

Federalism is the federal principle or system of government through which there are multiple governing bodies that have shared authority […]

What Is A Sand Dollar?

The term sand dollar refers to several species of flattened burrowing sea urchins that belong to the order Clypeasteroida. Sand dollars, […]

The Blind Spot – Reducing Knowledge Gaps In Urban Poverty With Earth Observation Interacting With Structured And Unstructured Geodata

We live in a period of one of the largest human migrations ever: the shift from rural to urban environments, […]

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?