Efficient syntheses of (−)-crinine and (−)-aspidospermidine, and the formal synthesis of (−)-minfiensine by enantioselective intramolecular dearomative cyclization. Issue 9 (12th July 2017)

• Record Type: Journal Article
• Authors: Du, Kang; Yang, He; Guo, Pan; Feng, Liang; Xu, Guangqing; Zhou, Qinghai; Chung, Lung Wa; Tang, Wenjun
• Is Part Of: Chemical science. Volume 8:Issue 9(2017)
• Page Start: 6247
• Page End: 6256
• Publication Date: 2017-07-12
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7sc01859b
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Palladium-catalyzed enantioselective dearomative cyclization has enabled the concise and enantioselective total syntheses of (−)-crinine and (−)-aspidospermidine, as well as a formal total synthesis of (−)-minfiensine. Abstract : Polycyclic alkaloids bearing all-carbon quaternary centers possess a diversity of biological activities and are challenging targets in natural product synthesis. The development of a general and asymmetric catalytic method applicable to the efficient syntheses of a series of complex polycyclic alkaloids remains highly desirable in synthetic chemistry. Herein we describe an efficient palladium-catalyzed enantioselective dearomative cyclization which is capable of synthesizing two important classes of tricyclic nitrogen-containing skeleton, chiral dihydrophenanthridinone and dihydrocarbazolone derivatives bearing all-carbon quaternary centers, in excellent yields and enantioselectivities. The P-chiral monophosphorus ligand AntPhos is crucial for the reactivity and enantioselectivity, and the choice of the N -phosphoramide protecting group is essential for the desired chemoselectivity. This method has enabled the enantioselective total syntheses of three distinctive and challenging biologically important polycyclic alkaloids, specifically a concise and gram-scale synthesis of (−)-crinine, an efficient synthesis of indole alkaloid (−)-aspidospermidine and a formal enantioselective synthesis of (−)-minfiensine.