Synthesis of Chiral Cyclophanes via Pd(II)-Catalyzed Atroposelective C-H Macrocyclization: Total Synthesis of
Lei Wang1, Yuan Xu1, Wen-Kui Yuan1
1State Key Laboratory of Soil Pollution Control and Safety, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.
Abstract:
Chiral cyclophanes are structurally intriguing macrocycles found in natural products and pharmaceuticals with promising biological activities. The development of efficient asymmetric macrocyclization strategies is therefore of great importance, yet remains a formidable challenge due to the entropic penalty and stereochemical complexities inherent to macrocyclization. Here, we report a palladium-catalyzed atroposelective C-H macrocyclization using l-tert-leucine as a chiral transient directing group. This method enables the efficient construction of a broad range of chiral cyclophanes with varied ring sizes in good yields (up to 88%) and excellent enantioselectivities (up to 99% ee) and further allows the dynamic kinetic resolution of prochiral macrocycles via intermolecular C-H olefination. The synthetic utility of this strategy is demonstrated by the asymmetric total synthesis of isoplagiochin D, which was completed in 10 linear steps with 16.8% overall yield and 97% ee.
More Related Videos
Related Concept Videos
Cycloaddition Reactions: Overview
Prochirality
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Stereoisomerism of Cyclic Compounds


![Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F60786.jpg&w=3840&q=50)