Synthesis of (−)-Stemoamide Using a Stereoselective <i>anti</i>-Aldol Step

Olivo, Horacio F.; Tovar-Miranda, Ricardo; Barragan, Efrain

doi:10.1021/jo052364l

Cited by 45 publications

(16 citation statements)

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“…The strategy developed by Olivo's group97g made use of a chiral auxiliary and relied on installation of the correct configurations at the three contiguous stereocenters (C‐8, C‐9, C‐9a) before the RCM step was performed (Scheme ). The diastereoselective addition of a Ti IV enolate of a chiral N ‐acyl thiazolidinethione ( 73 ) to a cyclic N ‐acyl iminium ion was thus used to prepare the adduct 72 with the necessary configuration at C‐9a, and 72 was then employed in an anti ‐aldol reaction with cinnamaldehyde, which provided the required configurations at C‐8 and C‐9.…”

Section: Synthetic Strategies In the Stemoamide And Tuberostemospimentioning

confidence: 99%

Strategies for the Synthesis of Stemona Alkaloids

Alibés

Figueredo

2009

Eur J Org Chem

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Keywords: Stemona alkaloids / Natural products / Synthesis design / Synthetic methods / AlkaloidsThe extracts of several plants of the Stemonaceae family have long been used in Asian countries against different diseases and for their antiparasitic properties. Significant constituents of these extracts are a series of structurally related secondary metabolites named Stemona alkaloids. All the Stemona alkaloids are polycyclic and contain multiple stereocenters. Most of them present a central pyrrolo[1,2-a]-azepine system and the majority also incorporate at least one α-methyl-γ-butyrolactone substructure. Their challenging molecular architectures have motivated the development of new strategies for the construction of their skeletons, but

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Section: Synthetic Strategies In the Stemoamide And Tuberostemospimentioning

confidence: 99%

Strategies for the Synthesis of Stemona Alkaloids

Alibés

Figueredo

2009

Eur J Org Chem

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“…This method has since been applied to the enantioselective total of (−)-stemoamide. 24 The key step in the synthesis was an anti-selective MgBr 2 ·Et 2 O-catalyzed aldol addition of a somewhat complex N-acylthiazolidinethione onto cinnamaldehyde (eq 20). This example illustrates the potential generality of the reaction in terms of thiazolidinethione employed since even this complex thioimide, with additional coordinating functionality in the molecule, performed well in the reaction.…”

Section: Use Of Mgbr 2 2 2 In Aldol Additions and Related Chemistrymentioning

confidence: 99%

Magnesium Bromide

Black¹,

Fader²

2007

Encyclopedia of Reagents for Organic Synthesis

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“…[15,16] Stemoamide, one of the Stemona alkaloids, was isolated from the Chinese traditional medicine Stemona tuberosa Lour by Xu and coworkers in 1992. [15,16] Stemoamide, one of the Stemona alkaloids, was isolated from the Chinese traditional medicine Stemona tuberosa Lour by Xu and coworkers in 1992.…”

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“…To demonstrate the synthetic value of this titanocenecatalyzed reaction, we developed an efficient six-step total synthesis of (AE)-9,10-diepi-stemoamide. [15,16] Stemoamide, one of the Stemona alkaloids, was isolated from the Chinese traditional medicine Stemona tuberosa Lour by Xu and coworkers in 1992. [17] Recently, the groups of Khim and Cossy have independently developed an asymmetric synthesis of (À)-9,10-diepi-stemoamide [15c] and a stereoselective synthesis of its racemat, [15a,b] respectively, by employing a 7-exo-trig radical ring-closure strategy.…”

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Umpolung of Hemiaminals: Titanocene‐Catalyzed Dehydroxylative Radical Coupling Reactions with Activated Alkenes

et al. 2013

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Bis(cyclopentadienyl)titanium(III) chloride (Nugents reagent) [1] is an efficient single-electron reductant and has been used as a versatile tool in organic synthesis, [2,3] owing to the ease of handling, its functional-group compatibility, and a broad array of reactions that can be effected under relatively mild conditions. Today, [Cp 2 TiCl] is used as a catalyst for several types of radical reactions by employing a catalytic amount of [Cp 2 TiCl 2 ] as a catalyst precursor and a metal (such as Mn, Zn, Al, In, Mg, and Sm) [4] as a coreductant in the presence of TMSCl or protic acids. Among the [Cp 2 TiCl]-catalyzed radical reactions, reductive epoxide opening reaction, [5] first demonstrated by Nugent and Rajan-Babu, [1] then by Gansäuer et al., [5b,c] has been the subject of intensive studies and found applications in natural product synthesis. [6] In this reaction, a [Cp 2 TiCl]-initialized homolysis of CÀO bonds is involved. As an extension of this feature, Barrero and co-workers recently described a deoxygenation of alcohols usually mediated by a stoichiometric amount of [Cp 2 TiCl]. In addition, catalytic examples have also been reported. [7] In view of these precedents, the [Cp 2 TiCl]catalyzed dehydroxylative coupling reactions of alcohols and other hydroxy-containing compounds, such as sugars, hemiacetals, and hemiaminals seemed possible.It is known that umpolung of hemiaminals can provide radical carbon intermediates in a position to amino groups through dehydroxylation and one-electron reduction of the corresponding carbenium ions. [8] We have recently developed a SmI 2 -mediated dehydroxylative radical cross-coupling reaction of hemiaminals with activated alkenes [Scheme 1, Eq. (1)], [9] which was assumed to proceed through a SmI 2based single-electron reduction of N-acyliminium ions. This methodology provides a useful and efficient strategy for C À C bond formation at the carbon atoms in a position to amino groups, and can be employed for the synthesis of alkaloids and other pharmaceuticals. [10] Based on these considerations, it would be particularly interesting and valuable to develop transition-metal-catalyzed dehydroxylative radical coupling reactions of hemiaminals under mild conditions, which have not been reported so far. We envisioned that the singular ability of [Cp 2 TiCl] to cleave a CÀO bond might help us to achieve this goal.Herein we report titanocene-catalyzed dehydroxylative radical coupling reactions of hemiaminals with activated alkenes [Scheme 1, Eq. (2)]. This novel reaction was performed by using a [Cp 2 TiCl 2 ] (cat.)/Mg/TMSCl reduction system [11] in the presence of tert-butanol. An application of this radical methodology has been demonstrated by an efficient synthesis of (AE)-9,10-diepi-stemoamide.We began our study with the treatment of hemiaminal 1 [12] and methyl acrylate (2.0 equiv) with [Cp 2 TiCl 2 ] (0.025 equiv), Mg powder (2.0 equiv), and TMSCl (2.0 equiv); the desired cross-coupling product 2 a was obtained in 54 % yield (Table 1, entry 1). The influence of othe...

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Synthesis of (−)-Stemoamide Using a Stereoselective anti-Aldol Step

Cited by 45 publications

References 17 publications

Strategies for the Synthesis of Stemona Alkaloids

Strategies for the Synthesis of Stemona Alkaloids

Magnesium Bromide

Umpolung of Hemiaminals: Titanocene‐Catalyzed Dehydroxylative Radical Coupling Reactions with Activated Alkenes

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