A Highly Efficient Large‐Scale Asymmetric Direct Intermolecular Aldol Reaction Employing <scp>L</scp>‐Prolinamide as a Recoverable Catalyst

Yang, Yang; He, Yan‐Hong; Guan, Zhi; Huang, Weida

doi:10.1002/adsc.201000355

Cited by 33 publications

(8 citation statements)

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“…Notwithstanding, catalyst 148 led to better results in the related reaction using tetrahydro-4H-pyran-4-one (140b) [199]. The use of catalyst 150 in the reaction between several acyclic and cyclic ketones and aromatic and heteroaromatic aldehydes provided the corresponding aldol products 54 in good results, and the catalyst was recovered and reused up to five times with only a slight decrease in the enantioselectivity ((3), Scheme 3.35) [200]. In the reaction between acetone and cyclohexanone and aromatic aldehydes, using (1-butyl-3-methylimidazolium)tetrafluoroborate ([bmim][BF 4 ])-water as the reaction media, bisprolinamide 151 was also recoverable up to five times without affecting the achieved results ((4), Scheme 3.35) [201].…”

Section: Proline Derivatives As Organocatalysts 189mentioning

confidence: 94%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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The use of catalytic enantioselective methods to perform an aldol reaction provides a direct entry for the synthesis of chiral compounds and is probably the most attractive way to achieve this goal with high control of the chemo-, regio-, diastereo-, and enantioselectivity. The application of biochemical methods based on enzyme aldolases or antibodies, which are discussed in other chapters, avoid the use of preformed enolates or their equivalents for enhancing the global atom efficiency of the process [1] for which the narrow substrate scope is a major drawback. The discovery of methodologies to carry out the enantioselective direct aldol reaction [2] has eluded the production of stoichiometric by-products increasing the substrate scope. This task could be accomplished by using small molecules as catalysts, such as metal complexes (which are covered along this book) and organic molecules, also known as organocatalysts [3]. The growth of this last research area and the direct aldol reaction are closely linked [4], with the report on the use of (S)-proline as catalyst for the intermolecular aldol [5] definitely being the push for the development of the organocatalytic methods as a competitive methodology for the synthesis of chiral compounds.In a strict sense, an organocatalyzed reaction is a process in which all the involved reagents and catalysis are purely organic compounds of low-molecular weight, excluding boron-and silicon-containing derivatives. However, in some cases, the presence of a silyl group only plays a steric role and therefore can also be considered as an organocatalyzed process. Also, if the organocatalyst involved in a reaction is immobilized in a polymer, a dendrimer, or even an inorganic material that serves only as a support to facilitate its recovery [6], it could still be considered as an organocatalyst, although those types of derivatives have been scarcely used in the natural product synthesis and therefore will be excluded from this chapter. Therefore, a comprehensive overview of the direct aldol reaction [7], emphasizing the reactivity, scope, selectivity, and limitations of the methodology and giving several examples of their application to the synthesis of biologically active compounds, is discussed in this chapter.

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Section: Proline Derivatives As Organocatalysts 189mentioning

confidence: 94%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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“…(Figure 3) 5 90 > 99 : 1 > 99 48 h/rt neat C. Qi 2013 [7] 3 2 -8 (Figure 3) 5 91 > 98 : 2 98 30 h/0 °C neat Alonso 2009 [8] 4 4 3-MBA [e] (5.0) Z. Guan 2010 [9] Cheong, Carter 2010 [10] [a] Catalyst number and establish. For this purpose, the reaction of isobutyraldehyde with the most studied ketone substrate, cyclohexanone, is summarized in Scheme 2, Figure 4, and Table 2.…”

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confidence: 99%

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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“…The catalyst can be recovered and reused with a slight loss of enantioselectivity after five cycles. The catalyst can be used in large‐scale reactions with maintained the enantioselectivity, which is great practice for industrial use …”

Section: Prolinamide Catalysed Direct Asymmetric Aldol Reactionmentioning

confidence: 99%

Prolinamide‐Catalysed Asymmetric Organic Transformations

2019

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Proline was reported as an enantioselective organocatalyst for direct asymmetric aldol reaction in the early 1971 s by two independent groups of researchers and the reaction was called the Hajos‐Parrish‐Eder‐ Sauer Wiechert reaction. The breakthrough of enantioselective organocatalysis was demonstrated by List and co‐workers in 2000 for intermolecular aldol reaction between benzaldehydes and ketone using proline as a catalyst. After this report many researchers were applied the proline as a catalyst for other organic transformation. The proline has a carboxylic functional group which can easily convert to the amide and known as prolinamide. Prolinamides were found to be a better catalyst compared to proline in the most of cases. In this review article we are compiling the results of the prolinamides catalyzed asymmetric organic transformation with insight of the mechanism of catalysis.

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A Highly Efficient Large‐Scale Asymmetric Direct Intermolecular Aldol Reaction Employing L‐Prolinamide as a Recoverable Catalyst

Cited by 33 publications

References 46 publications

Organocatalyzed Aldol Reactions

Organocatalyzed Aldol Reactions

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.

Prolinamide‐Catalysed Asymmetric Organic Transformations

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