No Transition Metals Required - Oxygen Promoted Synthesis of Imines from Primary Alcohols and Amines under Ambient Conditions

Abstract

The synthesis of imines denotes a cornerstone in organic chemistry. The use of alcohols as renewable substituents for carbonyl-functionality represents an attractive opportunity. Consequently, carbonyl moieties can be in situ generated from alcohols upon transition-metal catalysis under inert atmosphere. Alternatively, bases can be utilized under aerobic conditions. In this context, we report the synthesis of imines from benzyl alcohols and anilines, promoted by KO^t Bu under aerobic conditions at room temperature, in the absence of any transition-metal catalyst. A detailed investigation of the radical mechanism of the underlying reaction is presented. This reveals a complex reaction network fully supporting the experimental findings.

Keywords: DFT; imines; oxidation reactions; radical mechanisms; transition metal free.

Scheme 1

Transition metal catalyzed synthesis of imines from alcohols and amines (top) and base/oxygen promoted imine synthesis in the absence of a transition‐metal catalyst (bottom).

Scheme 2

¹⁸O‐Labeling experiment for the base/oxygen promoted synthesis of imines.

Scheme 3

Simplified reaction mechanism for the formation of benzaldehyde from benzyl alcohol through various pathways. The red O‐atoms represent the ¹⁸O‐labeling. The inserted EPR spectrum depicts a radical species (C or D) observed in experiment.

Figure 1

Simplified energy profiles of the various radical reaction pathways to form benzaldehyde. Paths A and B are water assisted, while path F denotes the water‐free pathway. The value for the transition state TS^EK−F is only an estimate, based on reaction path optimization. All values are free energies ΔG, in kcal/mol, calculated with DLPNO‐CCSD(T)/def2‐QZVP//PBE0/def2‐TZVP/D4. The ¹⁸O‐label is depicted in red. Due to the nature of CCSD, accurate energies are not achievable for the MECP points. In there cases, the energy differences are obtained from B2PLYP/def2‐TZVP/D4//PBE0/def2‐TZVP/D4 (for more information see computational methodology section and SI).