Oxidative Cross-Coupling of α-Amino Ketones with Alcohols Enabled by I2-Catalyzed C-H Hydroxylation
Yingwei Wang, Mingrong Yang, Chichou Lao, Hanxuan Wang and Zhihong Jiang*
*State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China,
Email: zhjiang
must.edu.mo
Y. Wang, M. Yang, C. Lao, H. Wang, Z. Jiang, J. Org. Chem., 2023, 88, 14470-14486.
DOI: 10.1021/acs.joc.3c01469
see article for more reactions
Abstract
An I2-catalyzed oxidative cross-coupling of α-amino ketones with a wide range of alcohols provides α-carbonyl N,O-acetals with high functional group tolerance. Using a combination of air and dimethyl sulfoxide as oxidants, the protocol allows an efficient late-stage modification of biorelevant structures. Moreover, the use of other nucleophiles enables additional functionalization of α-amino ketones.
see article for more examples
proposed mechanism
General Procedure for Oxidative Cross-Coupling of α-Amino Ketones with Nucleophiles
A screw-capped vial was charged with α-amino ketone (0.2 mmol, 1.0 equiv), nucleophile (unless otherwise noted, 0.24 mol, 1.2 equiv), I2 (10.2 mg, 0.04 mmol, 20 mol %), and DMSO (21.3 μL, 0.3 mmol, 1.5 equiv), followed by the addition of anhydrous CHCl3 (1 mL). The vial was tightly capped and stirred at 80 °C for 15 h in an oil bath. When the reaction was completed, the crude reaction mixture was allowed to reach room temperature. The solution was then quenched with 10% Na2S2O3 (2 mL) solution (w/w) and extracted with CH2Cl2 (2 × 4 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel to afford the desired product.
Key Words
α-hydroxylation, N,O-acetals, DMSO, oxygen
ID: J42-Y2023
