Nickel‐Catalyzed Enantioselective Synthesis of Dienyl Sulfoxide

• Published in: Angewandte Chemie Vol. 136; no. 5
• Main Authors: Gao, Li, Wang, Yin‐Qi, Zhang, Ya‐Qian, Fu, Yi‐Han, Liu, Yi‐Yu, Zhang, Qing‐Wei
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 25-01-2024
• Subjects: Asymmetric synthesis; Asymmetric S−C Bond Formation; Asymmetry; Carbonates; Catalysis; Chemical synthesis; Chemistry; Chiral Sulfoxide; DFT Calculation; Diels-Alder reactions; Dynamic Kinetic Resolution; Enantiomers; Esters; Heavy metals; Nickel; Outersphere; Pharmaceutical industry; Poisoning (reaction inhibition); Stereoselectivity; Sulfoxides; Transition metals
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202317626

Sulfoxides are widely used in the pharmaceutical industry and as ligands in asymmetric catalysis. However, the efficient asymmetric synthesis of this structural motif remains limited. In this study, we disclosed a Ni‐catalyzed enantioconvergent reaction that utilizes both racemic allenyl carbonates and β‐sulfinyl esters. Our method employs cheap and more sustainable Ni(II) as a precatalyst and successfully overcomes the challenging poisoning effect and instability of sulfenate generated in situ. This enables the synthesis of a series of dienyl sulfoxides with enantioselectivity of up to 98 % ee. The product exhibits tremendous potential in various applications, including diastereoselective Diels–Alder reactions, coordination with transition metals, and incorporation into medicinal compounds, among others. Using a combination of experimental and computational methods, we have uncovered an interesting associated outersphere mechanism that contrasts with conventional mechanisms commonly observed in asymmetric transition metal catalysis.
Nickel catalyzed asymmetric synthesis of dienyl sulfoxides were accomplished with up to 98 % ee from both racemic allenyl carbonates and β‐sulfinyl esters employing cheap Ni(II) as precatalyst. Experimental and computational methods revealed an interesting associated outersphere mechanism which is uncommon in transition metal catalyzed asymmetric allylic nucleophilic substitution reactions.