Copper(I)-catalyzed diastereo- and enantio-selective construction of optically pure exocyclic allenes

• Published in: Nature communications Vol. 11; no. 1; p. 4293
• Main Authors: He, Cheng-Yu, Tan, Yun-Xuan, Wang, Xin, Ding, Rui, Wang, Yi-Fan, Wang, Feng, Gao, Dingding, Tian, Ping, Lin, Guo-Qiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.08.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 140/131; 140/58; 639/638/403/933; 639/638/77/883; 639/638/77/888; Asymmetric synthesis; Asymmetry; Cascade chemical reactions; Chemical synthesis; Chemistry; Chinese medicine; Chirality; Construction; Copper; Functional groups; Humanities and Social Sciences; Laboratories; multidisciplinary; Natural products; Pharmaceuticals; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18136-x

Among about 150 identified allenic natural products, the exocyclic allenes constitute a major subclass. Substantial efforts are devoted to the construction of axially chiral allenes, however, the strategies to prepare chiral exocyclic allenes are still rare. Herein, we show an efficient strategy for the asymmetric synthesis of chiral exocyclic allenes with the simultaneous control of axial and central chirality through copper(I)-catalyzed asymmetric intramolecular reductive coupling of 1,3-enynes to cyclohexadienones. This tandem reaction exhibits good functional group compatibility and the corresponding optically pure exocyclic allenes bearing cis -hydrobenzofuran, cis -hydroindole, and cis -hydroindene frameworks, are obtained with high yields (up to 99% yield), excellent diastereoselectivities (generally >20:1 dr) and enantioselectivities (mostly >99% ee). Furthermore, a gram-scale experiment and several synthetic transformations of the chiral exocyclic allenes are also presented. Substantial efforts have been devoted to the construction of axially chiral allenes, however, the strategies to prepare chiral exocyclic allenes are still rare. This work describes a copper-catalyzed asymmetric synthesis of exocyclic allenes by simultaneous control of axial and central chirality.