Simple proline derivatives as recoverable catalysts for the large-scale stoichiometric aldol reactions

Li, Shi; Wu, Chuanlong; Long, Xiaoqin; Fu, Xiangkai; Chen, Guodong; Liu, Zhijian

doi:10.1039/c2cy00549b

Cited by 18 publications

(9 citation statements)

References 42 publications

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“…have been performed to excellent effect. [56,57,58] Similar scale accomplishments have been demonstrated for cyclopentanone and hydroxyacetone. [32b,59] Flow synthesis has also been considered and was recently reviewed for proline-based aldol reactions.…”

Section: Small and Large Scale In-water Reactions And Ball Millingmentioning

confidence: 74%

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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Section: Small and Large Scale In-water Reactions And Ball Millingmentioning

confidence: 74%

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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“…Proline is perhaps the most central catalytic scaffold within organocatalysis, and in analogy to the exploitation of the serine, threonine and cysteine amphiphiles just discussed, the application of proline amphiphiles prepared through acidic O -acylation reactions has also been exhaustively investigated [ 62 – 67 ]. The same research group that reported the comprehensive assortment of amphiphilic organocatalysts depicted in Scheme 10 also employed the same procedures on hydroxyproline ( Scheme 11 ) [ 62 ]. The O -diphenylacetoyl derivative was prepared using an analogous O -acylation procedure by Gruttadauria and co-workers in 2010 ( Scheme 11 ) [ 63 ].…”

Section: Reviewmentioning

confidence: 99%

“…These compounds proved very efficient as organocatalysts in asymmetric aldol reactions in aqueous media. Even catalyst recovery and reuse (up to seven cycles) for aldol reactions at large scale (200 mmol of substrate) were possible [ 62 ].…”

Section: Reviewmentioning

confidence: 99%

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Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

Kristensen¹

2015

Beilstein J. Org. Chem.

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SummaryAmino acids, whether natural, semisynthetic or synthetic, are among the most important and useful chiral building blocks available for organic chemical synthesis. In principle, they can function as inexpensive, chiral and densely functionalized starting materials. On the other hand, the use of amino acid starting materials routinely necessitates protective group chemistry, and in reality, large-scale preparations of even the simplest side-chain derivatives of many amino acids often become annoyingly strenuous due to the necessity of employing protecting groups, on one or more of the amino acid functionalities, during the synthetic sequence. However, in the case of hydroxyamino acids such as hydroxyproline, serine, threonine, tyrosine and 3,4-dihydroxyphenylalanine (DOPA), many O-acyl side-chain derivatives are directly accessible via a particularly expedient and scalable method not commonly applied until recently. Direct acylation of unprotected hydroxyamino acids with acyl halides or carboxylic anhydrides under appropriately acidic reaction conditions renders possible chemoselective O-acylation, furnishing the corresponding side-chain esters directly, on multigram-scale, in a single step, and without chromatographic purification. Assuming a certain degree of stability under acidic reaction conditions, the method is also applicable for a number of related compounds, such as various amino alcohols and the thiol-functional amino acid cysteine. While the basic methodology underlying this approach has been known for decades, it has evolved through recent developments connected to amino acid-derived chiral organocatalysts to become a more widely recognized procedure for large-scale preparation of many useful side-chain derivatives of hydroxyamino acids and related compounds. Such derivatives are useful in peptide chemistry and drug development, as amino acid amphiphiles for asymmetric catalysis, and as amino acid acrylic precursors for preparation of catalytically active macromolecular networks in the form of soluble polymers, crosslinked polymer beads or nanoparticulate systems. The objective of the present review is to increase awareness of the existence and convenience of this methodology, assess its competitiveness compared to newer and more elaborate procedures for chemoselective O-acylation reactions, spur its further development, and finally to chronicle the informative, but poorly documented history of its development.

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“…In spite of a variety of commercially available CSPs, most enantioseparations of aldols are reported on polysaccharide‐based selectors in which the sugar hydroxyls of the cellulose or amylose chiral backbone are derivatized with 3,5‐dimethylphenylcarbamate groups and specific compounds are better resolved on tris‐( S )‐α‐methylbenzylcarbamate amylose . Although optimal conditions for the analysis of a large number of chiral aldols have been developed in the context of the extensive research on asymmetric aldol reaction, a systematic study focused on the chromatographic features of this class of compounds on these CSPs is still missing.…”

Section: Introductionmentioning

confidence: 99%

Enantioseparation of aldols by high‐performance liquid chromatography on polysaccharide‐based chiral stationary phases that bear chlorinated substituents

Pedotti

Patti

2014

J of Separation Science

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Two families of aldols, obtained from the condensation of aromatic aldehydes with cyclohexanone or acetone (ten examples in each group), were analyzed by high-performance liquid chromatography in normal phase elution mode on three polysaccharide-based chiral stationary phases of the Lux series, namely, Lux Cellulose-2, Lux Cellulose-4 and Lux Amylose-2, which share the common feature of chlorinated substituents in the chiral selectors. Following simple optimization steps, the enantioseparation of all aldols derived from cyclohexanone was achieved and the highest values of separation factor (α, 1.32 < α < 2.20) and resolution (Rs , 4.5 < Rs <17.2) were observed on Lux Cellulose-2, with the only exception of the 4-nitro-substituted derivative that was better resolved on Lux Cellulose-4. On the contrary, Lux Amylose-2 was the best choice for aldols derived from acetone and only specific analytes in this group were resolved on the cellulose-based supports. A variable-temperature study of selected compounds allowed us to determine thermodynamic parameters of the enantioseparation process, which was enthalpy-controlled in all the cases except one.

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Simple proline derivatives as recoverable catalysts for the large-scale stoichiometric aldol reactions

Cited by 18 publications

References 42 publications

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.

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.

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

Enantioseparation of aldols by high‐performance liquid chromatography on polysaccharide‐based chiral stationary phases that bear chlorinated substituents

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