Selective Functionalization of 2-Amino-Azoles with Methanol and Ethanol Using a Pincer-(NHC)Mn(I) Complex

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Functionalization of heteroaromatic amines with alcohols presents synthetic challenges.
• Development of efficient and selective N-alkylation methods is crucial for accessing valuable chemical entities.

Purpose of the Study:

• To design a general and efficient protocol for the N-alkylation of heteroaromatic amines using alcohols.
• To explore the scope and limitations of the developed catalytic system.

Main Methods:

• Utilized a pincer-NHC carbene-based Mn(I) complex as the catalyst.
• Investigated the reaction with various 2-aminoazoles, aminopyridine, and aminoquinoline derivatives and a wide range of alcohols.
• Employed control experiments and density functional theory (DFT) calculations to elucidate the reaction mechanism.

Main Results:

• Achieved selective N-alkylation of diverse heteroaromatic amines with alcohols.
• Obtained good to excellent yields of monoalkylated products.
• Demonstrated the protocol's applicability in synthesizing bioactive molecules and enabling gram-scale synthesis.

Conclusions:

• The developed Mn(I)-catalyzed protocol provides an efficient and versatile approach for N-alkylation of heteroaromatic amines.
• The methodology broadens the synthetic utility of manganese catalysis in organic synthesis.
• The study offers valuable insights into the reaction pathway through mechanistic investigations.