Photoredox-catalyzed Direct Reductive Amination of Aldehydes without an External Hydrogen/Hydride Source

Abstract

The direct reductive amination of aromatic aldehydes has been realized using a photocatalyst under visible light irradiation. The single electron oxidation of an in situ formed aminal species generates the putative α-amino radical that eventually delivers the reductive amination product. This method is operationally simple, highly selective, and functional group tolerant, which allows the direct synthesis of benzylic amines by a unique mechanistic pathway.

Figure 1

Synthesis of aminal compound 5

Figure 2

Plausible mechanism for the reductive amination

Scheme 1

Photoredox-catalyzed reductive amination of aldehydes

Scheme 2. Reactivity of intermediate 5 under various conditions.^a

^a5 (1.0 equiv, 0.1 mmol), piperidine 3a (1.0 equiv), DIPEA (1.0 equiv), Ir catalyst 1 (2 mol %), MeCN-d₃ (0.20 M), rt, 24 h. ^bYield was determined by ¹H NMR using 1,3,5-trimethoxybenzene as an internal standard.

Scheme 3. Evaluation of Aldehydes and Amine Under Photoredox-Catalyzed Reductive Amination^a

^aGeneral reaction conditions: aldehyde 2 (1.0 equiv, 0.5 mmol), amine 3 (3.0 equiv, 1.5 mmol), B₂O₃ (1.0 equiv, 0.5 mmol), Ir-catalyst 1 (2 mol %), MeCN (0.20 M), rt, 24 h. ^bYield for the reaction using 2 equiv of amine. ^cYield for the 6.1 mmol scale reaction. ^dYield for the reaction (36 h) using 5 mol % 4CzIPN instead of 1. ^e10 mol % 2,6-dimethylbenzenethiol (7) was used. ^fYield for a 5.0 mmol scale reaction. ^gReaction time 48 h