Total Synthesis of (−)-Rhazinilam and Formal Synthesis of (+)-Eburenine and (+)-Aspidospermidine: Asymmetric Cu-Catalyzed Propargylic Substitution

Abstract

A total synthesis of (-)-rhazinilam and formal syntheses of (+)-eburenine and (+)-aspidospermidine that rely on a copper(I)-catalyzed asymmetric propargylic substitution as the key step are reported. A salient feature of the reaction is the asymmetric construction of a quaternary stereocenter in high yield and enantiomeric excess.

Diastereo‐ and Enantioselective Propargylation of 5H‐Thiazol‐4‐ones and 5H‐Oxazol‐4‐ones as Enabled by Cu/Zn and Cu/Ti Catalysis

“…Since the pioneering studies– of the groups of Murahashi, Marseeven, Nishibayashi, Hu, and many others, remarkable progress has been made in this APS reaction. The power of this reaction is also illustrated by its application in the total synthesis and direct functionalization, of natural products.…”

Synthetic Approaches to Tricyclic Aminoketones in the Total Synthesis of Aspidosperma and Kopsia Alkaloids

“…Tricyclic vinylogous amides are also received close attention from organic researchers because they can be converted into both cis ‐ or trans ‐CDE rings tricyclic aminoketones 1 under different conditions [24–28] . This synthetic strategy provides a powerful help for the determination of the configuration of 1 .…”

“…Therefore, this review will summarize the synthetic approaches to the tricyclic aminoketones 1 since 1963, including highlight the construction of the C‐/D‐/E‐ring with the all‐carbon quaternary stereogenic center, and subsequent give a brief introduction to complete the synthesis of aspidosperma and kopsia alkaloids. In addition, this review will discuss the formation of tricyclic aminoketones 1 based on their precursors, including tricyclic lactams, [10–23] tricyclic vinylogous amides, [24–28] tricyclic enones, [29–31] tricyclic ethers, [32] tricyclic ketals, [33] tricyclic esters, [34] and non‐tricyclic precursors [35–38] …”

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…Subsequent Fischer indolization with phenyl hydrazine resulted (+)‐eburenine 677 which upon further reduction yielded (+)‐aspidospermidine 678 (Scheme 166). [189] …”

“…Subsequent Fischer indolization with phenylh ydrazine resulted (+ +)-eburenine 677 which upon further reduction yielded( + +)-aspidospermidine 678 (Scheme 166). [189] In 2013, Banwell and co-workersr eportedt otal synthesis of Pimpinellin 680 by utilizing Au-catalyzed intramolecular hydroarylation reaction of benzofuran-tetheredp ropiolate ester 679. Transformation of 679 in presenceo f3mol %J ohnPhosAu(-MeCN)SbF 6 in CH 2 Cl 2 furnished Pimpinellin in 72 %y ield.…”