Palladium-catalyzed stereoselective construction of chiral allenes bearing nonadjacent axial and two central chirality

• Published in: Organic & biomolecular chemistry Vol. 21; no. 42; pp. 8516 - 852
• Main Authors: Liu, Li-Xia, Huang, Wen-Jun, Yu, Chang-Bin, Zhou, Yong-Gui
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.11.2023; Royal Society of Chemistry
• Subjects: Alkylation; Chemistry; Chemistry, Organic; Chirality; Flavonoids; Palladium; Physical Sciences; Science & Technology; Stereoselectivity; ASYMMETRIC-SYNTHESIS
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d3ob01315d

It is challenging to enantioselectively construct molecules bearing multiple nonadjacent stereocenters, in contrast to those bearing a single stereocenter or adjacent stereocenters. Herein, we report an enantio- and diastereoselective synthesis of substituted chiral allenes with nonadjacent axial and two central chiral centers through a combination of retro-oxa-Michael addition and palladium-catalyzed asymmetric allenylic alkylation. This methodology exhibits good functional-group compatibility, and the corresponding allenylic alkylated compounds, including flavonoid frameworks, are obtained with good yields and diastereoselectivities and excellent enantioselectivities (all >95% ee). Furthermore, the scalability of the current synthetic protocol was proven by performing a gram-scale reaction. An enantioselective synthesis of substituted chiral allenes with nonadjacent axial and two central chiral centers is reported, using a combination of retro-oxa-Michael addition and palladium-catalyzed asymmetric allenylic alkylation.