Enantioselective construction of cis -hydroindole scaffolds via an asymmetric inverse-electron-demand Diels–Alder reaction: application to the formal total synthesis of (+)-minovincine

• Published in: Chemical science (Cambridge) Vol. 13; no. 19; pp. 5562 - 5567
• Main Authors: Zhang, Fangqing, Ren, Bing-Tao, Zhou, Yuqiao, Liu, Yangbin, Feng, Xiaoming
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 18.05.2022; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Asymmetry; Chemistry; Chemistry, Multidisciplinary; Diels-Alder reactions; Enantiomers; Functional groups; Natural products; Physical Sciences; Scaffolds; Science & Technology; Stereoselectivity; VINCA ALKALOIDS; LIGANDS; NATURAL-PRODUCTS; CYCLOADDITIONS; CHEMISTRY; BIOMIMETIC ALKALOID SYNTHESES; OCTAHYDROINDOLES; COORDINATION; MATCHED 2-PYRONES; CYCLIZATION
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/D2SC01458K

cis -Hydroindole scaffolds widely exist in a large number of natural products, pharmaceuticals, and organocatalysts. Therefore, the development of efficient and enantioselective methods for the construction of cis -hydroindoles is of great interest and importance. Herein, a novel approach for the enantioselective synthesis of cis -hydroindole scaffolds has been realized through a chiral N , N ′-dioxide/Mg(OTf) 2 complex catalyzed asymmetric inverse-electron-demand Diels–Alder (IEDDA) reaction of 2-pyrones and cyclic enamines. A series of substituted cis -hydroindole derivatives bearing multiple contiguous stereocenters and functional groups were obtained in good to excellent yields and enantioselectivities (up to 99% yield, and 95% ee) under mild reaction conditions. Moreover, the enantioselective formal total synthesis of (+)-minovincine was concisely furnished with high efficiency and stereoselectivity to demonstrate the synthetic potential of this method.