Enantioselective Synthesis of (−)-Anaferine Dihydrochloride by a Ruthenium-Catalysed Tandem Ring Rearrangement Metathesis

Blechert, Siegfried; Stapper, Christian

doi:10.1002/1099-0690(200208)2002:16<2855::aid-ejoc2855>3.0.co;2-1

Cited by 23 publications

(8 citation statements)

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“…This mild reducing agent was preferred to the most common LiAlH 4 , to avoid the conversion of the two Boc protecting groups into methyl amines [28]. The TBS protecting group was selectively cleaved using TBAF, affording the known intermediate 16, reported in Blechert and Stapper's synthesis of (-)-anaferine [24].…”

Section: Resultsmentioning

confidence: 99%

“…The last total synthesis of (-)-anaferine was accomplished in 2002 by Stapper and Blechert [24], while del Pozo et al recently reported the preparation of the (+)-enantiomer [25] (Figure 3). Stapper and Blechert's strategy took advantage of an enantiopure cycloheptene precursor, accessed in five steps from the commercially available tropone.…”

Section: Introductionmentioning

confidence: 99%

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Total Synthesis of (–)-Anaferine: A Further Ramification in a Diversity-Oriented Approach

et al. 2020

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The piperidine ring is a widespread motif in several natural bioactive alkaloids of both vegetal and marine origin. In the last years, a diversity-oriented synthetic (DOS) approach, aimed at the generation of a library of piperidine-based derivatives, was developed in our research group, employing commercially available 2-piperidine ethanol as a versatile precursor. Here, we report the exploration of another ramification of our DOS approach, that led us to the stereoselective total synthesis of (–)-anaferine, a bis-piperidine alkaloid present in Withania somnifera extract. This natural product was obtained in 9% overall yield over 13 steps, starting from a key homoallylic alcohol previously synthesised in our laboratory. Therefore, the collection of piperidine-derivatives accessible from 2-piperidine ethanol was enriched with a new, diverse scaffold.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Total Synthesis of (–)-Anaferine: A Further Ramification in a Diversity-Oriented Approach

et al. 2020

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“…Like other RRM reactions discussed, oligomerization is an important side reaction, which may be suppressed by the use of an ethylene atmosphere and by performing the reaction at higher dilution. and 84 led to the core of (−)-anaferine [41], (+)-dihydrocuscohygrine, and cuscohygrine [42] by just modifying the N-alkenyl chain length (Scheme 11.23). Tandem RRM was carried out under an inert atmosphere with catalyst [Ru]-I in refluxing CH 2 Cl 2 and provided bis-tetrahydropyridine derivative 85 after 48 hours in 87% yield.…”

Section: Rcm-rom-rcmmentioning

confidence: 99%

Cascade Metathesis in Natural Product Synthesis

Porta

Blechert

2010

Metathesis in Natural Product Synthesis

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IntroductionAlkene metathesis is well established as a valuable synthetic tool in organic chemistry, and has proven to be a unique technique for the construction of complex structures in a rapid and effective way [1]. Since all metathesis transformations (except diyne metathesis) can be promoted by the same carbene catalysts, it is possible to combine them in a sequential way and enable a metathesis cascade in one pot. A domino reaction has been defined as ''a process involving two or more bond-forming transformations which take place under the same reaction conditions without additional reagents and catalysts, and in which the subsequent reactions result as a consequence of the functionality formed in the previous step'' [2]. These domino processes, also called tandem, provide a tremendous increase in molecular complexity within the use of one single catalyst in one pot. By carefully adjusting the conditions and judicious choice of the catalytic complex, it is often possible to conduct the process with excellent regio-, chemo-, diastereo-, and even enantioselectivity. Domino processes are especially attractive not only because they provide elegance to the synthetic route but also for being ecologically and economically favorable since they minimize the amount of waste, solvents, reagents, and energy compared to stepwise reactions. Much effort has been invested in developing new methodologies involving metathesis domino processes that have been successfully applied to the preparation of biologically active and naturally occurring molecules. In this chapter, a selection of synthetic approaches with ruthenium-catalyzed domino reactions that include exclusively metathesis steps will be discussed, whereby syntheses involving tandem reactions connecting a metathesis reaction with a reaction of a different type [3] or several metathesis transformations occurring independently at the same time will not be described [4]. Through this collection of natural product syntheses, we would like to highlight the high efficiency and utility of metathesis domino reactions in organic synthesis, discuss its driving forces, limits, and scope, and ultimately illustrate the enormous synthetic potential of this transformation.

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“…The utility of strained disubstituted cycloheptenes in alkaloid syntheses is highlighted by Blechert's total syntheses of the bis-pyrrolidine alkaloid (+)-dihydrocuscohydrine (390) [161], the bis-piperidine alkaloid (-)-anaferin (in the form of its dihydrochloride 393) [162], and indolizine 167B (397) [163] (Scheme 77).…”

Section: Metathesis On Solid Supportmentioning

confidence: 99%

Diene, Enyne, and Diyne Metathesis in Natural Product Synthesis

Mulzer

Öhler²

2005

ChemInform

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Enantioselective Synthesis of (−)-Anaferine Dihydrochloride by a Ruthenium-Catalysed Tandem Ring Rearrangement Metathesis

Abstract: A stereoselective synthesis of (−)-anaferine dihydrochloride has been developed. The bis(tetrahydropyridine) system 10 was formed by a tandem ring rearrangement metathesis of the chiral bis(but-3-enylamino)cycloheptene derivative 9.

Cited by 23 publications

References 4 publications

Total Synthesis of (–)-Anaferine: A Further Ramification in a Diversity-Oriented Approach

Total Synthesis of (–)-Anaferine: A Further Ramification in a Diversity-Oriented Approach

Cascade Metathesis in Natural Product Synthesis

Diene, Enyne, and Diyne Metathesis in Natural Product Synthesis

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