Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan

Pirola, Margherita; Puglisi, Alessandra; Raimondi, Laura; Forni, Alessandra; Benaglia, Maurizio

doi:10.3390/molecules24122260

Cited by 5 publications

(2 citation statements)

References 27 publications

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“…Benaglia et al [29] reported the stereoselective synthetic strategy for the preparation of trifluoromethylamine mimics of retro thiorphan, an inhibitor of metalloproteinase NEP (neutral endopeptidase). The crucial step is the stereoselective, catalytic reduction of a fluorinated enamine with trichlorosilane as a reducing agent in the presence of a chiral Lewis base.…”

Section: Homogenous Organocatalysis In Flowmentioning

confidence: 99%

Stereoselective organocatalysis and flow chemistry

Puglisi

Rossi

2021

Physical Sciences Reviews

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Organic synthesis has traditionally been performed in batch. Continuous-flow chemistry was recently rediscovered as an enabling technology to be applied to the synthesis of organic molecules. Organocatalysis is a well-established methodology, especially for the preparation of enantioenriched compounds. In this chapter we discuss the use of chiral organocatalysts in continuous flow. After the classification of the different types of catalytic reactors, in Section 2, each class will be discussed with the most recent and significant examples reported in the literature. In Section 3 we discuss homogeneous stereoselective reactions in flow, with a look at the stereoselective organophotoredox transformations in flow. This research topic is emerging as one of the most powerful method to prepare enantioenriched products with structures that would otherwise be challenging to make. Section 4 describes the use of supported organocatalysts in flow chemistry. Part of the discussion will be devoted to the choice of the support. Examples of packed-bed, monolithic and inner-wall functionalized reactors will be introduced and discussed. We hope to give an overview of the potentialities of the combination of (supported) chiral organocatalysts and flow chemistry.

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Section: Homogenous Organocatalysis In Flowmentioning

confidence: 99%

Stereoselective organocatalysis and flow chemistry

Puglisi

Rossi

2021

Physical Sciences Reviews

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“…In addition, fluorinated compounds are present in about 20% of drugs [20][21][22]. In general, the introduction of fluorine atoms or fluoroalkyl (perfluoroalkyl) groups into heterocyclic compounds increases lipophilicity, stability, solubility, reactivity, and biological properties [23][24][25][26][27]. Accordingly, the combination of two pharmacophoric entities such as the thiazolo-or oxazolo [3,2-a]pyrimidin-7-one scaffold and perfluoroalkyl groups could be an effective method to enhance the biological activity of these heterocycles.…”

Section: Introductionmentioning

confidence: 99%

Simple and Expedient Access to Novel Fluorinated Thiazolo- and Oxazolo[3,2-a]pyrimidin-7-one Derivatives and Their Functionalization via Palladium-Catalyzed Reactions

et al. 2022

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An efficient, versatile, and one-pot method for the preparation of novel fluorinated thiazolo- and oxazolo[3,2-a]pyrimidin-7-ones is described from 2-aminothiazoles or 2-amino-oxazoles and fluorinated alkynoates. This transformation, performed under transition-metal-free conditions, offers new fluorinated cyclized products with good to excellent yields. Moreover, the functionalization of these N-fused scaffolds via the Suzuki-Miyaura and Sonogashira cross-coupling reactions led to the synthesis of highly diverse thiazolo- and oxazolo[3,2-a]pyrimidin-7-ones.

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Enantioselective Organocatalytic Addition of Nitromethane to Trifluoromethyl Aryl Ketimines Promoted by Electron‐Rich Bifunctional Iminophosphoranes

et al. 2023

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Thiourea-based iminophosphorane (BIMP) organocatalysts featuring SPhos-or BI-DIME phosphine units have been developed and successfully applied in the asymmetric addition of nitromethane to N-Boc-protected trifluoromethyl aryl ketimines. α-Trifluoromethyl β-nitroamines were obtained in 40-82% isolated yields and 80-95% enantioselectivities. A careful evaluation of the catalytic activity of BIMPs indicates that the catalysts derived from the combination via Staudinger reaction of a chiral 1,2-amino alcoholderived thiourea-organoazide with electron-rich phosphines, promote the aza-Henry reaction on fluorinated ketimines with the highest enantioselectivity, leading to the amine featuring a tetrasubstituted stereocenter in up to 95% ee. The reaction was performed also on gram scale, without loss of enantioselectivity.

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Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan

Cited by 5 publications

References 27 publications

Stereoselective organocatalysis and flow chemistry

Stereoselective organocatalysis and flow chemistry

Simple and Expedient Access to Novel Fluorinated Thiazolo- and Oxazolo[3,2-a]pyrimidin-7-one Derivatives and Their Functionalization via Palladium-Catalyzed Reactions

Enantioselective Organocatalytic Addition of Nitromethane to Trifluoromethyl Aryl Ketimines Promoted by Electron‐Rich Bifunctional Iminophosphoranes

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