Photocatalytic regioselective four-component radical relay carbonylation for α-aminoketones synthesis

Abstract

Regioselective transformation is among the long-standing challenges in organic synthesis, particularly involving gas trapping. We present here a novel photocatalytic strategy for the regioselective carbonylation reaction toward α-aminoketones. Experimental studies reveal that protonic acids dissociated from protonated amines facilitate the reactions of low-reactive aldehydes and enhance the electrophilicity of imines, thereby promoting the efficient coupling of less nucleophilic acyl radicals. This approach introduces a reliable framework for controlling regioselectivity in photocatalytic multi-radical-coupled CO trapping reactions, broadens the chemical space of α-aminoketones, and advances carbonylation reactions for sustainable development.

Fig. 1. Background of regioselective multi-radical reaction and our design.

Scheme 1. Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), 3 (0.24 mmol), CHCl₃ (2.0 mL), CO (40 bar), PC-2 (1.5 mol%), under 400–500 nm irradiation, at 30 °C for 24 h. Isolated yield.

Scheme 2. Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), 3 (0.24 mmol), CHCl₃ (2.0 mL), CO (40 bar), PC-2 (1.5 mol%), under 400–500 nm irradiation, at 30 °C for 24 h. Isolated yield.

Scheme 3. Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), 3 (0.24 mmol), CHCl₃ (2.0 mL), CO (40 bar), PC-2 (1.5 mol%), under 400–500 nm irradiation, at 30 °C for 24 h. Isolated yield.

Scheme 4. Radical capture experiments, and exploration of influencing factors of catalytic system. 1a, 2a and 3a: (f) CHCl₃ (0.1 M), CO (40 bar), PC-2 (1.5 mol%), under 400–500 nm irradiation, at 30 °C for 15 h. (g) 1a/2a/3a = 1/1/1.5, CHCl₃ (0.1 M), PC-2 (1.5 mol%), under 400–500 nm irradiation, at 30 °C for 15 h. Isolated yield.

Scheme 5. Plausible reaction mechanism for the photocatalytic regioselective carbonylation.