Aerobic Aliphatic Hydroxylation Reactions by Copper Complexes: A Simple Clip-and-Cleave Concept.

Area of Science:

• Organic Chemistry
• Catalysis
• Biomimetic Chemistry

Background:

• Selective functionalization of non-activated C-H bonds remains a significant challenge in organic synthesis.
• Developing efficient catalytic systems for oxidation reactions is crucial for sustainable chemistry.

Purpose of the Study:

• To develop a novel method for the selective hydroxylation of non-activated C-H bonds in aliphatic aldehydes.
• To utilize a copper complex and dioxygen as the oxidant for this transformation.

Main Methods:

• Formation of an imine from an aldehyde and N,N-diethyl-ethylenediamine.
• Complexation of the imine with a copper(I) salt to form a bidentate ligand complex.
• Reaction of the copper complex with dioxygen followed by acidic cleavage and workup.

Main Results:

• Selective β-hydroxylation of various aliphatic aldehydes, including trimethylacetaldehyde, adamantane, and diamantane 1-carbaldehydes, was achieved.
• High selectivities for the desired β-hydroxy aldehydes were obtained.
• Low-temperature stopped-flow measurements identified a bis(μ-oxido)dicopper complex as a key intermediate.

Conclusions:

• The developed imine clip-and-cleave concept provides an efficient route for selective C-H hydroxylation.
• Computational studies (DFT) support a concerted hydroxylation mechanism with low activation barriers, explaining the observed regioselectivity.