Enyne diketones as substrate in asymmetric Nazarov cyclization for construction of chiral allene cyclopentenones

• Published in: Nature communications Vol. 13; no. 1; pp. 3146 - 11
• Main Authors: Tang, Shengbiao, Zhang, Peng, Shao, Ying, Sun, Jiangtao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.06.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/403/935; 639/638/549/972; 639/638/77/883; Alkynes; Allene; Asymmetric synthesis; Asymmetry; Catalysis; Diketones; Enantiomers; Humanities and Social Sciences; Isomerization; multidisciplinary; Relay; Rhodium; Science; Science (multidisciplinary); Stereoselectivity; Substrates; Synthesis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-30846-y

The Nazarov cyclization is one of the most powerful tools for the stereoselective synthesis of various cyclopentenone scaffolds. Therefore, developing the new classes substrate of Nazarov reaction is an important endeavor in synthetic chemistry. Herein, we report enyne diketones, enables diastereo- and enantioselective construction of chiral allene cyclopentenones in moderate to good yields with good enantioselectivities (up to 97% ee). Importantly, it is a typical example for asymmetric synthesis of cyclopentanones with allene moiety using Nazarov cyclisation. Mechanistic studies indicate that this metal-organo relay catalysis protocol involves a rhodium-catalyzed tandem oxonium ylide formation/[2,3]-sigmatropic rearrangement/reverse benzylic acid rearrangement, followed by organo-catalyzed asymmetric Nazarov cyclization/alkyne-to-allene isomerization to give the final chiral allene cyclopentenones. Developing classes of substrates for the Nazarov reaction is an important endeavour for synthetic chemistry. Here, the authors report how enyne diketones undergo rhodium-catalyzed metal-organo relay catalysis for the enantioselective construction of chiral allene cyclopentenones via Nazarov cyclisation in good yields and enantioselectivities.