Enantioselective Synthesis of Oxazocines via MQ‐Phos Enabled Palladium‐Catalyzed Asymmetric Formal [4+4]‐Cycloadditions

Autor: Qiaojing Meng, Yinggao Meng, Qinglin Liu, Bing Yu, Zhong‐Jun Li, Er‐Qing Li, Junliang Zhang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 31, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
DOI: 10.1002/advs.202402170
Popis: Abstract Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long‐standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP‐Ligand P‐chiral stereocenter is first designed and synthesized, called MQ‐Phos, and successfully applied it in the Pd‐catalyzed enantioselective higher‐order formal [4+4]‐cycloaddition of α, β‐unsaturated imines with 2‐(hydroxymethyl)‐1‐arylallyl carbonates. The reaction features mild conditions, excellent regio‐ and enantiocontrol and a broad substrate scope (54 examples). Various medium‐sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ‐Phos is critical for synthesis of the medium‐sized ring in excellent catalytic reactivity and enantioselectivity.
Databáze: Directory of Open Access Journals
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