Synthesis of a new chiral organocatalyst derived from (S)-proline containing a 1,2,4-triazolyl moiety and its application in the asymmetric aldol reaction. Importance of one molecule of water generated in situ

Sánchez-Antonio, Omar; Juaristi, Eusebio

doi:10.1016/j.tetlet.2019.151128

Cited by 10 publications

(5 citation statements)

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“…Thus, seeking to increase the reactivity of the halide as leaving group for SN 2 reactions, a Finkelstein-type reaction was carried out on (3-chloropropyl)triethoxysilane 1 to obtain the corresponding iodide derivative 2 in quantitative yield [ 82 ]. Siloxyiodide 2 was subjected to an SN 2 substitution reaction with thiol ( S )- 3 (synthetized according to the previously described procedure [ 74 ]) under basic conditions to obtain thioether ( S )- 4 in 72% yield. Subsequently 1.0 mmol of thioether ( S )- 4 was exposed to 2.64 g of commercial silica and heated to reflux for 24 h. The silica-supported derivative ( S )- 5 was filtered and treated with five drops of conc.…”

Section: Resultsmentioning

confidence: 99%

“…Table 1 summarizes the outcome of the reactions that were carried out initially. First, and according to previous work [ 74 ] it was assumed that best results would be observed under neat conditions or in the presence of water. However, as it can be appreciated in entries 1 and 2, although reaction yields were quite high, the observed stereoselectivities turned out to be low.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, our research group recently reported the preparation of three novel and efficient ( S )-proline-derived organocatalysts containing a 1,2,4-triazolyl-5-thione moiety, that proved highly efficient in asymmetric aldol reactions [ 74 ]. Relevantly, this organocatalytic system does not require of the presence of any additive to accomplish the desired transformation affording an eco-friendly protocol that avoids extra purification procedures to obtain the corresponding aldol products.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, one can take advantage of the 1,2,4-triazole moiety as a hydrogen bridge inducer to potentially anchor electrophilic aldehydes used in the aldol reaction (see ref. [ 74 ] for more details about the reaction’s mechanism and the synthesis of the catalyst).…”

Section: Introductionmentioning

confidence: 99%

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New Mesoporous Silica-Supported Organocatalysts Based on (2S)-(1,2,4-Triazol-3-yl)-Proline: Efficient, Reusable, and Heterogeneous Catalysts for the Asymmetric Aldol Reaction

et al. 2020

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Novel organocatalytic systems based on the recently developed (S)-proline derivative (2S)-[5-(benzylthio)-4-phenyl-(1,2,4-triazol)-3-yl]-pyrrolidine supported on mesoporous silica were prepared and their efficiency was assessed in the asymmetric aldol reaction. These materials were fully characterized by FT-IR, MS, XRD, and SEM microscopy, gathering relevant information regarding composition, morphology, and organocatalyst distribution in the doped silica. Careful optimization of the reaction conditions required for their application as catalysts in asymmetric aldol reactions between ketones and aldehydes afforded the anticipated aldol products with excellent yields and moderate diastereo- and enantioselectivities. The recommended experimental protocol is simple, fast, and efficient providing the enantioenriched aldol product, usually without the need of a special work-up or purification protocol. This approach constitutes a remarkable improvement in the field of heterogeneous (S)-proline-based organocatalysis; in particular, the solid-phase silica-bonded catalytic systems described herein allow for a substantial reduction in solvent usage. Furthermore, the supported system described here can be recovered, reactivated, and reused several times with limited loss in catalytic efficiency relative to freshly synthesized organocatalysts.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

New Mesoporous Silica-Supported Organocatalysts Based on (2S)-(1,2,4-Triazol-3-yl)-Proline: Efficient, Reusable, and Heterogeneous Catalysts for the Asymmetric Aldol Reaction

et al. 2020

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“…Juaristi et al ., [62] reported triazole‐substituted proline derivative 77 as a catalyst for asymmetric aldol reaction. Reduced yield and compromised stereoselectivity by protonation of the organocatalyst 77 or by adding water to the reaction medium implied that acidic/basic additives are unnecessary for the reaction.…”

Section: Proline‐derived Hybrid Catalystsmentioning

confidence: 99%

Stereoselective Aldol and Conjugate Addition Reactions Mediated by Proline‐Based Catalysts and Its Analogues: A Concise Review

2021

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The application of amino acids and small peptides as asymmetric organocatalysts in the aldol and conjugate addition reactions is a significant breakthrough in the past decade. The desired stereoselectivity in these reactions can be attained through tunable elements of diversity present in the amino acids/peptides. On this note, the current review highlights the organocatalytic aldol and conjugate addition by proline or its analogous in the form of amide/peptide derivatives. The wide‐ranging works of literature are classified based on the use of single amino acid or peptides as a catalyst. The designing of the aforementioned amide/amino acid/peptide catalyst, including their recent applications, is also detailed. Moreover, the analogous catalysts are also discussed, embedding other hetero‐organic functionalities that mimic the catalytic activity of proline in aldol/conjugate additions.

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A 2000 to 2020 Practitioner's Guide to Chiral Amine‐Based Enantioselective Aldol Reactions: Ketone Substrates, Best Methods, in Water Reaction Environments, and Defining Nuances.

et al. 2022

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An extensive introduction is provided for the non-expert regarding enantioselective, amine catalyzed, aldol reactions (Sections 1-3). There, a broad perspective is provided regarding: methodology limitations, mechanism, in-water versus on-water definitions and their theoretical basis, small-and large-scale physical-mechanical aspects, solid versus liquid starting material considerations, reproducibility, ball milling, diketone substrates, etc. The thematic emphasis then turns to practical outcomes for the reaction of nineteen aliphatic, cyclic, and aromatic ketones with 4-nitrobenzaldehyde and benzaldehyde prior to 2021. In doing so, 172 catalysts are highlighted. The ketone substrates are listed in the Table of Contents (Section 4) and their structures are shown in Figure 1. Each ketone is summarized by a: (i) schematic, (ii) text summary, (iii) catalyst Figures, and (iv) tabular reaction/ product data. Individual ketone summaries, at times, represent the distillation of over six hundred and fifty research articles, and the data refinement and its tabular reconstitution is not reproducible using a chemical database search with filters. In the review's broadest use, the Figure 1 ketone structures serve as templates to extrapolate to hypothetical substrates holding more functionality, but of related steric and electronic similarity. This pseudo matching permits a rapid answer to, "Does this methodology suit the ketone substrate at hand or not?" In a positive outcome, the best reaction conditions (stoichiometry, catalyst structure and loading, solvent, time, etc.) to affect aldol product formation (yield, dr, and ee) are delineated. A second envisioned use, allows the directed construction of diketone substrates (after viewing the tabularized data of Section 4) capable of undergoing regioselective mono-aldol product formation. This ketone regioselectivity tactic, reacting one carbonyl moiety while the other remains unreacted, avoids ketone protection-deprotection, and is demonstrated for the advantageous synthesis of an Alzheimer drug candidate.

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Synthesis of a new chiral organocatalyst derived from (S)-proline containing a 1,2,4-triazolyl moiety and its application in the asymmetric aldol reaction. Importance of one molecule of water generated in situ

Cited by 10 publications

References 50 publications

New Mesoporous Silica-Supported Organocatalysts Based on (2S)-(1,2,4-Triazol-3-yl)-Proline: Efficient, Reusable, and Heterogeneous Catalysts for the Asymmetric Aldol Reaction

New Mesoporous Silica-Supported Organocatalysts Based on (2S)-(1,2,4-Triazol-3-yl)-Proline: Efficient, Reusable, and Heterogeneous Catalysts for the Asymmetric Aldol Reaction

Stereoselective Aldol and Conjugate Addition Reactions Mediated by Proline‐Based Catalysts and Its Analogues: A Concise Review

A 2000 to 2020 Practitioner's Guide to Chiral Amine‐Based Enantioselective Aldol Reactions: Ketone Substrates, Best Methods, in Water Reaction Environments, and Defining Nuances.

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