Cr-Catalyzed Asymmetric Cross Aza-Pinacol Couplings for β-Amino Alcohol Synthesis
Hui Hu and Zhaobin Wang*
*Zhejiang Province Department of Chemistry, School of Science, Westlake University, Hangzhou 310030, China,
Email: wangzhaobin
westlake.edu.cn
H. Hu, Z. Wang, J. Am. Chem. Soc., 2023, 145, 20775-20781.
DOI: 10.1021/jacs.3c08493
see article for more reactions
Abstract
A Cr-catalyzed asymmetric cross aza-pinacol coupling of aldehydes and N-sulfonyl imines provides β-amino alcohols bearing vicinal stereocenters. This protocol proceeds in a radical-polar crossover manner from the intermediacy of an α-amino radical instead of a ketyl radical.
see article for more examples
proposed mechanism
Reductive coupling of aldehydes and imines (for aromatic aldehydes)
Reaction set-up: In a nitrogen filled gloved box, an oven-dried 4 mL vial was charged with CrCl2 (3.7 mg, 0.03 mmol, 15 mmol%), ligand (10.6 mg) and a magnetic stir bar (3*12 mm). DME (1.0 mL) was added via a pipette. The mixture was stirred at room temperature for 2 hours. Next, Mn powder (22.0 mg, 0.4 mmol, 2.0 equiv), aldehyde (0.3 mmol, 1.5 equiv), imine (0.2 mmol, 1.0 equiv) and Cp2ZrCl2 (116.9 mg, 0.4 mmol, 2.0 equiv) were added sequentially. The vial was closed with a PTFE septum cap and taken out of the glove-box. The resulting suspension was stirred at room temperature for 48 hours.
Reaction work-up: After completion, 200 μL H2O was added to the reaction mixture. After stirring at room temperature for 10 min, the reaction mixture was filtered through a pad of silica gel. The solvent was concentrated in vacuo, the residue was purified by preparative TLC on silica gel to provide the desired product.
Reductive coupling of aldehydes and imines (for aliphatic aldehydes)
Reaction set-up: In a nitrogen filled gloved box, an oven-dried 4 mL vial was charged with CrCl2 (3.7 mg, 0.03 mmol, 15 mmol%), ligand (10.6 mg) and a magnetic stir bar (3*12 mm). DME (1.0 mL) was added via a pipette. The mixture was stirred at room temperature for 2 hours. Next, Mn powder (22.0 mg, 0.4 mmol, 2.0 equiv), LiBF4 (18.8 mg, 0.2 mmol, 1.0 equiv), aldehyde (0.4 mmol, 2.0 equiv), imine (0.2 mmol, 1.0 equiv) and Cp2ZrCl2 (116.9 mg, 0.4 mmol, 2.0 equiv) were added sequentially. The vial was closed with a PTFE septum cap and taken out of the glove-box. The resulting suspension was stirred at 50°C for 24 hours.
Reaction work-up: After completion, 200 μL H2O was added to the reaction mixture. After stirring at room temperature for 10 min, the reaction mixture was filtered through a pad of silica gel. The solvent was concentrated in vacuo, the residue was purified by preparative TLC on silica gel to provide the desired product.
Key Words
pinacol coupling, β-amino alcohols, Schwartz's reagent, manganese
ID: J48-Y2023
