Efficient syntheses of (−)-crinine and (−)-aspidospermidine, and the formal synthesis of (−)-minfiensine by enantioselective intramolecular dearomative cyclization

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.

Recent Advances in Synthetic Strategies for the C4a,C9a-Fused Tetracyclic Hydrocarbazole Core Structure of Minfiensine and Related Akuammiline Alkaloids

“…Tang and co-workers reported a synthesis of tetracyclic hydrocarbazole 65 via palladium-catalyzed asymmetric dearomative cyclization of diarylamine 58 followed by intramolecular cyclization of allylic alcohol 63 derived from dienone 60 (Scheme 11). 44 Specifically, they performed palladium-catalyzed asymmetric dearomative cyclization of diarylamine of 58 to obtain dienone 60 in 63% yield with 90% ee.…”

Synthetic Approaches to Tetracyclic Indolines as Versatile Building Blocks of Diverse Indole Alkaloids

“…In 2017, Tang and co‐workers reported an enantioselective palladium‐catalyzed intramolecular dearomative cyclization for the synthesis of tetracyclic indoline skeleton . As depicted in Scheme , a palladium‐catalyzed Buchwald‐Hartwig amination of o ‐dibromobenzene with aniline 157 , obtained from commercially available starting material 156 through N‐protection generated the compound 158 .…”

“… A palladium‐catalyzed enantioselective dearomative cyclization approach to tetracyclic indoline 162 (Tang et al …”

“…In 2017, Ta ng andc o-workersr eported an enantioselective palladium-catalyzed intramolecular dearomativec yclization for the synthesis of tetracyclic indoline skeleton. [50] As depicted in Scheme 19, ap alladium-catalyzed Buchwald-Hartwiga mination of o-dibromobenzene with aniline 157,o btained from commerciallya vailables tartingm aterial 156 through N-protection generated the compound 158.T hen, the introduction of the N-phosphoramide group and deprotection of the methoxy group are essential for the achievemento fe xcellent chemoselectivity in the palladium-catalyzed intramolecular dearomative cyclization. [51] The fourth ring was introduced by aTMSOTf-promotedd eprotection of Boc group and an in situ intramolecular aza-Michael addition cascade reaction.…”

The Chemical Synthesis of the Crinine and Haemanthamine Alkaloids: Biologically Active and Enantiomerically-Related Systems that Serve as Vehicles for Showcasing New Methodologies for Molecular Assembly

“…The synthesis of (−)-crinine [(−)- 26 ] reported in 2017 by Tang [ 102 , 103 ] employs an intriguing variation of the para-para -biaryl coupling that has featured extensively in the biomimetic syntheses of the title alkaloids. The route starts ( Scheme 52 ) with a reductive amination reaction between the bromopiperonal 340 and aniline 398 that produces the 2°-amine 399 .…”