Rhodium-Catalyzed Asymmetric Addition to 4- or 5-Carbonyl-cycloenones through Dynamic Kinetic Resolution: Enantioselective Synthesis of (-)-Cannabidiol
Wen-Cong Li, He Meng, Jialin Ming*, Shufeng Chen*
*Inner Mongolia Key Laboratory of Fine Organic Synthesis, Inner Mongolia University, 235 West University Street, Hohhot 010021, China,
Email: mingjialin
imu.edu.cn, shufengchenimu.edu.cn
W.-C. Li, H. Meng, J. Ming, S. Chen, Org. Lett., 2024, 26, 1366-1369.
DOI: 10.1021/acs.orglett.3c04281
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Abstract
Reactions of 4/5-carbonyl-cycloalkenones with organoboronic acids in the presence of a chiral diene (S,S)-Fc-tfb-rhodium catalyst gave disubstituted trans-cycloalkanones with high diastereo- and enantioselectivity. This highly efficient dynamic kinetic resolution is achieved by fast racemization of the substrate through the formation of a dienolate followed by kinetic resolution by the catalyst.
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ligand
proposed reaction pathway
Details
The document discusses a study on the rhodium-catalyzed asymmetric addition to 4- or 5-carbonylcycloenones through dynamic kinetic resolution (DKR), leading to the enantioselective synthesis of (−)-cannabidiol (CBD). The reaction involves 4/5-carbonyl-cycloalkenone 1 or its achiral isomer 1′ with organoboronic acid 2 in the presence of a chiral diene (S,S)-Fc-tfb-rhodium catalyst, producing disubstituted trans-cycloalkanone 3 with high diastereo- and enantioselectivity. This method achieves high efficiency through fast racemization of 1 via dienolate formation followed by kinetic resolution with the chiral catalyst. The study demonstrates the utility of this method by synthesizing key intermediates for biologically active compounds, including (−)-CBD and tetrahydrocannabinol (THC). The optimized conditions and substrate scope are detailed, showing high yields and excellent stereoselectivity. The method's synthetic practicability is highlighted by reducing the rhodium catalyst amount in a gram-scale reaction, maintaining high yield and selectivity. Mechanistic studies and control experiments provide insights into the reaction process, confirming the high efficiency and selectivity of the DKR method. The study concludes with the potential applications of this method in synthesizing key precursors for various biologically active compounds.
Key Words
ID: J54-Y2024
