Technical articles
Why Small Molecules Can Also Serve as Catalysts: Judging Organocatalytic Systems from Reaction Objectives and Activatable Structural Sites
Why Small Molecules Can Also Serve as Catalysts: Judging Organocatalytic Systems from Reaction Objectives and Activatable Structural Sites
1. What Is an Organocatalyst?
Organocatalysts are catalysts whose active component is a small organic molecule. They do not rely on transition-metal centers, and they are different from the macromolecular active sites found in enzymatic catalysis. They can promote reactions because their molecular structures contain functional units capable of activating substrates. For example, secondary amines can react with carbonyl substrates such as aldehydes and ketones to form enamine or iminium intermediates, thereby changing the nucleophilicity or electrophilicity of the substrate. Thiourea molecules often interact with substrates through hydrogen bonding, helping electrophilic substrates enter a more reactive state. Such small molecules do not merely “participate in the reaction”; instead, they change the reaction pathway through specific modes of interaction, lower the activation energy of key steps, and regenerate within the catalytic cycle. When chiral organocatalysts are used, they can also influence the stereoselectivity of the product.
The core reason small molecules can act as catalysts is that they can change how a substrate reacts:
Role of the small-molecule catalyst | Effect on the substrate | Representative catalytic mode |
Forms transient covalent intermediates with the substrate | Changes the nucleophilicity or electrophilicity of the substrate | Enamine catalysis, iminium catalysis, N-heterocyclic carbene catalysis |
Forms hydrogen bonds or ion pairs with the substrate | Organizes substrate conformation and improves selectivity | Hydrogen-bond donor catalysis, chiral Brønsted acid catalysis |
Helps ions transfer between different phases | Promotes reactions in biphasic or solid–liquid systems | Phase-transfer catalysis |
Provides a chiral spatial environment | Induces formation of a specific enantiomer or diastereomer | Chiral organocatalysis |
The 2021 Nobel Prize in Chemistry was awarded to Benjamin List and David W. C. MacMillan for their contributions to the development of asymmetric organocatalysis. The official Nobel Prize materials describe asymmetric organocatalysis as a third type of catalysis built on small organic molecules.
2. First Clarify the Reaction Task: What Bond Is to Be Formed, and Which Site Is to Be Activated?
When selecting an organocatalytic system, the reaction task should be clarified first, rather than starting from the catalyst name. It is necessary to determine what bond needs to be formed in this step, which site’s reactivity needs to be changed, or what type of transformation needs to be completed. Only after identifying the structural site in the substrate that needs activation can one further judge whether to choose enamine catalysis, iminium catalysis, hydrogen-bond donor catalysis, phase-transfer catalysis, N-heterocyclic carbene catalysis, or an organic oxidation catalytic system.
Bond-forming or transformation objective | Common substrates | Organocatalytic direction to consider first | Key question |
Formation of a carbon–carbon bond or carbon–heteroatom bond at the α-position of a carbonyl compound | Aldehydes and ketones with α-hydrogens | Enamine catalysis | Is the goal to turn the carbonyl α-position into a nucleophilic reaction site? |
Addition or cycloaddition at the β-position of a conjugated system | α,β-Unsaturated aldehydes, and some conjugated carbonyl substrates capable of forming iminium intermediates with amine catalysts | Iminium catalysis | Is the goal to enhance the electrophilicity of the conjugated system through an iminium intermediate? |
Selective addition to imines, nitroalkenes, or activated alkenes | Electrophilic substrates that can be activated by hydrogen bonding or acid catalysis | Hydrogen-bond donor catalysis, chiral Brønsted acid catalysis | Is mild electrophile activation and stereoselectivity control required? |
Alkylation, substitution, or addition under biphasic or solid–liquid conditions | Active methylene compounds, phenols, thiols, and inorganic-base systems | Phase-transfer catalysis | Are ion transfer and interfacial mass transfer key issues? |
Reversal of the normal polarity of an aldehyde or acyl precursor | Aldehydes, enals, and acyl-related substrates | N-heterocyclic carbene catalysis | Is it necessary to form an acyl anion equivalent? |
3. Then Examine the Activatable Site in the Substrate: Where Does the Catalyst Act?
When selecting an organocatalytic system, it is not enough to ask whether the substrate is an aldehyde, ketone, imine, or alkene. It is also necessary to identify which structural site in the substrate can be recognized, bound, or activated by the catalyst. This site may be called the activatable structural site in the substrate. It determines which catalytic pathway the reaction is more likely to enter.
Activatable structural site in the substrate | Possible catalytic mode | Applicability judgment |
Aldehydes or ketones with α-hydrogens | Enamine catalysis | Suitable for converting the carbonyl α-position into a nucleophilic reaction site; used in aldol reactions, Mannich reactions, Michael additions, and α-functionalization |
α,β-Unsaturated aldehydes, and some conjugated carbonyl substrates capable of forming iminium intermediates with amine catalysts | Iminium catalysis | Suitable for enhancing β-position electrophilicity through an iminium intermediate, promoting conjugate addition, cycloaddition, or cascade reactions |
Electrophilic acceptors such as imines, nitroalkenes, and maleimides | Hydrogen-bond donor catalysis, chiral Brønsted acid catalysis | Suitable for organizing substrates through hydrogen bonding, protonation, or ion pairing, thereby improving reactivity and controlling stereoselectivity |
Deprotonatable substrates such as active methylene compounds, phenols, and thiols | Phase-transfer catalysis | Suitable for liquid–liquid biphasic or solid–liquid reactions involving inorganic bases; used in alkylation, substitution, and addition reactions |
Aldehydes, enals, and related acyl precursors | N-heterocyclic carbene catalysis | Suitable for forming acyl anion equivalents, acyl azoliums, or related active intermediates; used in umpolung, acyl transfer, and cyclization reactions |
The same substrate may contain multiple activatable structural sites. For example, an α,β-unsaturated aldehyde contains both a carbonyl group and a conjugated double bond. It may undergo iminium activation to enhance β-position electrophilicity, but it may also enter other activation pathways under specific catalytic systems. Therefore, before choosing a catalyst, one should first clarify where the target reaction is expected to occur: a carbonyl-related transformation, conjugate addition, remote functionalization, or acyl transfer. Only after identifying the structural site on which the catalyst truly acts can the subsequent choice of enamine catalysis, iminium catalysis, hydrogen-bond donor catalysis, phase-transfer catalysis, or N-heterocyclic carbene catalysis be justified.
4. Judging by Catalytic Mode: What Problems Do Different Systems Solve?
4.1 Enamine Catalysis: Making the Carbonyl α-Position Nucleophilic
Enamine catalysis is commonly used for aldehydes and ketones containing α-hydrogens. A secondary amine catalyst forms an enamine intermediate with the carbonyl substrate, making the α-carbon behave as a nucleophilic site. This allows the substrate to participate in aldol reactions, Mannich reactions, Michael additions, and α-functionalization. In 2000, List and co-workers reported the proline-catalyzed direct asymmetric aldol reaction, which became one of the representative works in the development of modern asymmetric organocatalysis.
Situations where it should be considered first | Basis for judgment |
Direct bond formation at the α-position of an aldehyde or ketone | The substrate has α-hydrogens |
Avoidance of preformed strongly basic enolates | The substrate can form an enamine under relatively mild conditions |
Construction of a chiral center | A chiral secondary amine or amino acid catalyst can provide an asymmetric environment |
Situations where it should not be considered first | Reason |
The substrate has no α-hydrogen | It is difficult to form an enamine intermediate |
The substrate is highly prone to self-condensation or polymerization | Background reactions may interfere with catalytic control |
The substrate or product is sensitive to acids or bases | Decomposition, racemization, or side reactions may occur |
4.2 Iminium Catalysis: Enhancing the Electrophilicity of Conjugated Acceptors
Iminium catalysis is commonly used for α,β-unsaturated aldehydes and some conjugated carbonyl substrates capable of forming iminium intermediates with amine catalysts. After a chiral amine catalyst forms an iminium ion with the substrate, the electrophilicity of the conjugated system is enhanced, making it easier for nucleophiles or dienes to participate in the reaction. The highly enantioselective organocatalytic Diels–Alder reaction reported by MacMillan’s group in 2000 is a representative example of using a chiral amine to catalyze reactions of α,β-unsaturated aldehydes.
Situations where it should be considered first | Basis for judgment |
The conjugated acceptor needs to undergo nucleophilic attack | The substrate contains an α,β-unsaturated carbonyl structure |
The target reaction occurs at the β-position | The electrophilicity of the conjugated system needs to be enhanced |
Enantioselectivity needs to be controlled | A chiral amine catalyst can provide an asymmetric environment |
4.3 Hydrogen-Bond Donor Catalysis: Activating Electrophilic Substrates through Weak Interactions
Hydrogen-bond donor catalysis commonly relies on structures such as thioureas, ureas, and squaramides. These catalysts form one or more hydrogen bonds with the substrate, thereby enhancing electrophile reactivity and organizing the transition state. Small-molecule hydrogen-bond donors have become an important research direction in asymmetric catalysis. Thioureas and related hydrogen-bond donors are often used to activate imines, nitroalkenes, maleimides, and some carbonyl acceptors.
Substrates or systems where it should be considered first | Reason for applicability |
Imines, nitroalkenes, and maleimides | Electrophilicity can be enhanced through hydrogen bonding |
Substrates containing multiple hydrogen-bond acceptor sites | Directional binding can be formed more readily |
Substrates sensitive to strong acids, strong bases, or metal conditions | Activation can be achieved in a milder manner |
Hydrogen-bond donor catalysis relies on relatively weak noncovalent interactions. If the substrate cannot form effective hydrogen bonds, or if the system contains large amounts of competing hydrogen-bond donors or acceptors, the catalytic effect may decrease.
4.4 Chiral Brønsted Acid Catalysis: Providing Both Acid Activation and a Chiral Ionic Environment
Chiral Brønsted acid catalysis is commonly used for imines, acetals, enamine precursors, and systems capable of forming cationic or ion-pair intermediates. Chiral phosphoric acids are representative catalysts. They can influence both reactivity and stereoselectivity through Brønsted acidity, hydrogen bonding, ion pairing, and related modes of interaction.
Situations where it should be considered first | Basis for judgment |
Mild acid activation is needed | The substrate can be activated by protonation or hydrogen bonding |
Cationic or ion-pair intermediates need to be controlled | Reaction selectivity depends on the spatial organization of ion pairs |
The substrate contains imines, acetals, or related activatable structures | Controlled intermediates may be formed |
4.5 Phase-Transfer Catalysis: Solving Ion Transfer in Biphasic or Solid–Liquid Systems
Phase-transfer catalysis is commonly used in systems where an organic phase and an aqueous phase coexist, or where a solid base and an organic substrate are both present. Quaternary ammonium salts, phosphonium salts, crown ethers, and their chiral derivatives can help ionic reactants enter the organic phase or interfacial region, thereby promoting alkylation, substitution, Michael addition, and related reactions. Asymmetric phase-transfer catalysis has developed many organic transformations catalyzed by chiral onium salts and crown ethers.
Systems where it should be considered first | Basis for judgment |
Use of inorganic bases or inorganic salts | Active ions may have difficulty entering the organic phase |
The substrate and base are distributed in different phases | The reaction is affected by the phase interface and mass transfer |
Strong homogeneous base conditions need to be avoided | The concentration of active species can be controlled through the interface |
4.6 N-Heterocyclic Carbene Catalysis: Achieving Umpolung
N-heterocyclic carbene catalysis is often used for “umpolung” reactions. Umpolung refers to making a carbon center that normally behaves as an electrophilic site behave as a nucleophilic site under the action of a catalyst. N-heterocyclic carbenes can form Breslow intermediates with aldehyde substrates, giving aldehydes the reactivity of acyl anion equivalents and allowing them to participate in benzoin condensation and Stetter reactions. In other systems, N-heterocyclic carbenes can also form intermediates such as acyl azoliums, which are used in acyl transfer, cyclization, and cascade reactions.
Situations where it should be considered first | Basis for judgment |
An acyl anion equivalent is needed | The substrate usually contains an aldehyde or related acyl precursor |
Conventional electrophilic addition pathways cannot directly solve the problem | The inherent polarity of the substrate needs to be changed |
Acylation, cyclization, or tandem products need to be constructed | Catalytic intermediates can participate in multiple consecutive transformations |
5. Which Conditions Should Be Checked First during Experimental Screening?
After a catalytic mode has been selected, experimental success usually depends on whether the reaction conditions match the activation mode. The following variables should be checked first during initial screening.
Screening item | Question to answer | Main influence |
Catalyst loading | Does the current substrate require a relatively high catalyst concentration to initiate the reaction? | Conversion, selectivity, scale-up cost |
Catalyst salt form or activation method | When using a free base, hydrochloride, ammonium salt, imidazolium salt, or thiazolium salt, are bases, acids, or other additives needed to release the active catalytic species? | Initiation efficiency and side reactions in amine catalysis, N-heterocyclic carbene catalysis, and organic base catalysis |
Solvent | Does it favor intermediate formation, hydrogen bonding, or ion pairing? | Activity, selectivity, solubility |
Water content | Does water promote, suppress, or disrupt the catalytic cycle? | Iminium formation, hydrogen bonding, substrate stability |
Acid/base additives | Do they promote formation of the key intermediate? | Reaction rate, side reactions, substrate stability |
Temperature | Is the current priority to improve conversion or maintain selectivity? | Rate, enantioselectivity, side reactions |
Concentration | Are self-condensation, polymerization, or background reactions present? | Chemoselectivity, reproducibility |
Order of addition | Is it necessary to reduce the instantaneous concentration of a certain component? | Side-reaction control, exotherm control |
Stirring and phase behavior | Are there biphasic or solid–liquid mass-transfer limitations? | Phase-transfer catalysis results, scale-up stability |
6. Where Are the Advantages of Organocatalysis?
6.1 It Can Combine Substrate Activation with Chiral Control
Many organocatalysts can both activate substrates and provide a chiral environment. Therefore, in asymmetric synthesis, organocatalysis is often used to construct chiral centers directly. The official Nobel Prize materials also point out that asymmetric organocatalysis can be used to selectively construct a specific mirror-image form of a molecule.
6.2 It Helps Reduce Issues Related to Metal Residues
Organocatalysts themselves usually do not contain transition-metal centers. This has practical significance in pharmaceutical intermediates, fine chemicals, and projects sensitive to metal impurities. This does not mean that the process is necessarily greener, but it does reduce the category of problems related to metal-residue control.
6.3 It Makes It Easier to Build a Screening Logic Based on the Reaction Task
Different organocatalytic modes correspond to different reaction problems:
Catalytic mode | Main question addressed |
Enamine catalysis | How to make the carbonyl α-position behave as a nucleophilic site |
Iminium catalysis | How to enhance the electrophilicity of a conjugated acceptor |
Hydrogen-bond donor catalysis | How to activate an electrophilic substrate through weak interactions |
Chiral Brønsted acid catalysis | How to achieve both acid activation and control by a chiral ionic environment |
Phase-transfer catalysis | How to solve ion transfer and interfacial reaction problems |
N-heterocyclic carbene catalysis | How to achieve umpolung |
6.4 It Can Align with Green Chemistry Goals, but Each Case Must Be Evaluated Separately
Organocatalysis is often associated with green chemistry. This association has a real basis, but it should not be simplified into the idea that “organocatalysis is greener as long as it is used.” Whether a process truly meets green chemistry goals depends on catalyst loading, solvent, reaction time, purification method, waste generation, and feasibility of scale-up.
7. When Should Organocatalysis Not Be the First Choice?
Situation | Why caution is needed |
The substrate has no clearly defined activatable site | The catalyst may have difficulty effectively recognizing or changing the substrate’s reactivity |
The background reaction is too fast | The catalyst may have difficulty controlling selectivity |
The substrate is highly sensitive to acid, base, or water | Decomposition, racemization, or side reactions may occur |
Catalyst loading remains difficult to reduce over time | Scale-up cost and purification pressure may increase |
The product and catalyst are difficult to separate | Workup becomes complicated and process value is affected |
A shorter and more robust metal-catalyzed or enzyme-catalyzed route already exists | There is no need to abandon a mature route merely for the sake of using organocatalysis |
8. Product Navigation Table for Small-Molecule Organocatalytic Systems: Selecting Tables 1–6 by Research or Experimental Objective
Research or experimental objective | Recommended table to check first | Why this table should be checked first | Recommended table for cross-reference | Navigation notes |
Establish an initial screening system for reactions involving biphasic systems, solid–liquid systems, or inorganic bases | Table 1 | Table 1 focuses on quaternary ammonium salts, crown ethers, and cinchona alkaloid frameworks, making it suitable for first judging whether the reaction is limited by ion transfer, interfacial mass transfer, or salt solubility | Table 5 | If the reaction also requires deprotonation by an organic base or nucleophilic catalysis, Table 5 can be consulted to compare organic-base and phase-transfer catalytic conditions |
Study α-position bond formation of aldehydes and ketones, such as aldol reactions, Mannich reactions, and α-functionalization | Table 2 | Table 2 focuses on proline, hydroxyproline, pipecolic acid, and prolinol derivatives, making it suitable for building a screening system around nucleophilic activation at the carbonyl α-position | Table 5 | If the reaction is sensitive to acid–base conditions, Table 5 can be consulted to examine the effects of organic bases, nucleophilic catalysts, and reaction environment on conversion |
Study conjugate addition, cycloaddition, or cascade reactions of α,β-unsaturated aldehydes | Table 2 | The imidazolidinone and prolinol silyl ether catalysts in Table 2 are suitable for iminium activation systems, allowing evaluation of enhanced β-position electrophilicity and chiral induction | Tables 3 and 4 | If the substrate also involves acid activation or hydrogen-bond recognition, Tables 3 and 4 can be consulted to compare noncovalent activation pathways |
Study imines, acetals, cationic intermediates, or ion-pair-controlled reactions | Table 3 | Table 3 focuses on BINOL-derived chiral phosphoric acids, which are suitable for imine activation, acetal activation, ion-pair control, and asymmetric acid-catalyzed reactions | Table 4 | If the substrate is suitable for hydrogen-bond-directed activation and does not require obvious acid activation, Table 4 can be consulted to compare thiourea-type hydrogen-bond donor catalytic systems |
Study hydrogen-bond donor catalysis, bifunctional catalysis, and noncovalent activation | Table 4 | Table 4 focuses on diaryl thioureas, chiral thiourea–tertiary amines, and cinchona alkaloid-derived thioureas, which are suitable for screening electrophilic substrate activation through hydrogen bonding and chiral addition reactions | Tables 3 and 1 | If the reaction requires acid activation, Table 3 can be consulted; if phase interfaces or ion transfer are involved, Table 1 can be consulted |
Study aldehyde umpolung, benzoin condensation, Stetter reactions, or acyl transfer | Table 5 | Table 5 lists carbene precursors such as thiazolium salts, imidazolium salts, and thiamine hydrochloride, which are suitable for reactions involving acyl anion equivalents, umpolung, and acyl transfer | Tables 2 and 3 | If the substrate also involves α-position activation of aldehydes or ketones, Table 2 can be consulted; if acidic additives or chiral acids are involved, it is necessary to first evaluate whether they inhibit N-heterocyclic carbene formation before deciding whether to use an acid–base cooperative strategy |
Study organic base catalysis, nucleophilic catalysis, esterification, acylation, or deprotonative activation | Table 5 | Table 5 includes diazabicyclooctane, diazabicycloundecene, triazabicyclodecene, and dimethylaminopyridine, making it suitable for comparing basicity, nucleophilicity, and acyl-transfer ability | Table 1 | If inorganic salts, inorganic bases, or phase interfaces have a significant effect on the reaction, Table 1 can be consulted to examine the cooperative effects of phase-transfer catalysts or crown ethers |
Study selective oxidation of alcohols, hydrogen atom transfer, or small-molecule organic oxidation catalysis | Table 6 | Table 6 focuses on nitroxyl radicals and N-hydroxyimide-type oxidative catalyst precursors, which are suitable for screening conditions for alcohol oxidation, benzylic oxidation, and radical oxidation | Table 5 | If the oxidation system requires a base, nucleophilic catalyst, or acid–base regulation, Table 5 can be consulted to optimize reaction conditions |
Compare the effect of catalyst configuration on product enantioselectivity | Tables 2, 3, and 4 | These three tables include multiple pairs of enantiomers or chiral frameworks, which can be used to observe how catalyst configuration, steric hindrance, and hydrogen-bonding sites affect product configuration | Table 1 | If the reaction occurs in a biphasic system, Table 1 can be consulted to judge whether the phase-transfer process affects chiral control |
Establish an initial screening route for small-molecule organocatalysis based on activatable structural sites in the substrate | Tables 2–6 | The carbonyl α-position, conjugated acceptors, electrophilic substrates, ionic substrates, aldehyde-derived acyl precursors, and oxidation substrates correspond to different tables, allowing rapid positioning of catalytic systems based on substrate structure | Table 1 | When the reaction involves inorganic bases, inorganic salts, biphasic systems, or solid–liquid systems, Table 1 should also be checked to avoid judging reaction success only from catalyst structure |
Table 1｜Phase-Transfer Catalysts, Crown Ethers, and Chiral Phase-Transfer Catalytic Frameworks
Category | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Quaternary ammonium phase-transfer catalyst | 32503-27-8 | Tetrabutylammonium hydrogensulfate (TBAHS) | Anhydrous, ≥97% | Acidic quaternary ammonium salt that can promote anion entry into the organic phase; suitable for screening base-mediated alkylation, substitution, and Michael addition systems | |
Crown ether ion-pair regulator | 17455-13-9 | 18-Crown-6 | Ion-pair chromatography grade, ≥99% (GC) | Shows pronounced coordination ability toward potassium ions; can modify salt solubility and ion-pairing states; used for solid–liquid phase transfer and activation of anionic reactions | |
Quaternary ammonium phase-transfer catalyst | 1112-67-0 | Tetrabutylammonium chloride | Ion-pair chromatography grade, ≥99% | Common tetrabutylammonium salt suitable for initial screening of liquid–liquid or solid–liquid phase-transfer conditions; used in nucleophilic substitution, alkylation, and interfacial reactions | |
Quaternary ammonium phase-transfer catalyst | 1643-19-2 | Tetrabutylammonium bromide | Ion-pair chromatography grade, ≥99% | Common bromide quaternary ammonium salt that can improve effective transfer of inorganic salts or anions into the organic phase; suitable for comparing phase-transfer catalytic conditions | |
Quaternary ammonium phase-transfer catalyst | 311-28-4 | Tetrabutylammonium iodide (TBAI) | Ion-pair chromatography grade | Iodide quaternary ammonium salt that can participate in halide exchange and phase-transfer promotion; used for screening halide substitution, etherification, and alkylation reactions | |
Quaternary ammonium phase-transfer catalyst | 71-91-0 | Tetraethylammonium bromide | Ion-pair chromatography grade | Small-volume tetraethylammonium salt suitable for comparing the effects of ammonium salt hydrophobicity and ion-transfer ability on phase-transfer reactions | |
Chiral phase-transfer catalytic framework | 118-10-5 | (+)-Cinchonine | Moligand™, ≥98% | Cinchona alkaloid chiral framework that can be used in the design and preparation of chiral quaternary ammonium salts, thioureas, and bifunctional organocatalysts | |
Chiral phase-transfer catalytic framework | 56-54-2 | Quinidine | Moligand™, ≥98%, contains 5–15% dihydroquinidine | Cinchona alkaloid chiral framework that can be used to construct asymmetric phase-transfer catalysts and bifunctional organocatalysts | |
Chiral phase-transfer catalytic framework | 485-71-2 | Cinchonidine | Moligand™, ≥98% | Cinchona alkaloid chiral framework commonly used in derivatization studies of chiral ammonium salts, chiral bases, and hydrogen-bond donor catalysts | |
Chiral phase-transfer catalytic framework | 130-95-0 | Quinine | Moligand™, ≥97% | Natural chiral cinchona alkaloid framework that can be used for developing chiral phase-transfer catalysts, thiourea catalysts, and bifunctional catalysts | |
Benzyl quaternary ammonium phase-transfer catalyst | 56-37-1 | Benzyltriethylammonium chloride | ≥98% | Benzyl quaternary ammonium salt commonly used in phase-transfer catalysis for anion transfer, nucleophilic substitution, and screening of base-promoted reaction conditions | |
Crown ether ion-pair regulator | 14187-32-7 | Dibenzo-18-crown-6 | ≥98% | Aryl-substituted crown ether that can regulate metal cation coordination and anionic reactivity; used in studies of ion-pairing effects | |
Benzyl quaternary ammonium phase-transfer catalyst | 23616-79-7 | Benzyltributylammonium chloride (BTBAC) | ≥98% | Hydrophobic benzyl quaternary ammonium salt suitable for promoting anion transfer and interfacial reactions in the organic phase; used in alkylation and substitution reactions | |
Benzyl quaternary ammonium phase-transfer catalyst | 56-93-9 | Benzyltrimethylammonium chloride (TMBAC) | ≥98% | Small-volume benzyl quaternary ammonium salt that can be used to compare the effects of ammonium salt structure on phase-transfer efficiency, phase behavior, and reaction rate | |
Crown ether ion-pair regulator | 33100-27-5 | 15-Crown-5 | ≥97% | Common crown ether for sodium-ion coordination; can modify the effective anionic reactivity in sodium salt systems; used in solid–liquid phase-transfer reactions |
Table 2｜Enamine Catalysis, Iminium Catalysis, and Chiral Amine Catalysts
Category | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Proline-type enamine catalyst | 147-85-3 | L-Proline | UltraBio™, ≥99.5% | Classical small-molecule chiral amine catalyst; can be used in studies of aldol reactions, Mannich reactions, and carbonyl α-functionalization | |
Proline-type enamine catalyst | 344-25-2 | D-Proline | Moligand™, ≥99% | Proline enantiomer that can be used to compare the effects of catalyst configuration on carbonyl α-position bond formation and product configuration | |
Proline-derived enamine catalyst | 51-35-4 | trans-4-Hydroxy-L-proline | Moligand™, ≥99% | Hydroxyproline-containing derivative that can be used in structural modification of chiral amine catalysts and in studies of carbonyl reaction conditions | |
Cyclic amino acid enamine catalyst | 3105-95-1 | L-Pipecolic acid | ≥98% | Six-membered cyclic amino acid framework that can be used to compare the effects of ring size on enamine formation, reaction activity, and stereochemical induction | |
Chiral secondary amine catalyst | 112068-01-6 | S474479 | (S)-(−)-α,α-Diphenyl-2-pyrrolidinemethanol | 99% | Diphenylprolinol framework that can be used to develop aldehyde/ketone enamine catalysis and conjugated acceptor iminium activation systems |
Chiral secondary amine catalyst | 848821-76-1 | (S)-α,α-Bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrolidinemethanol | ≥98% | Strongly electron-withdrawing aryl-substituted prolinol framework that can be used to adjust steric hindrance and electronic effects in chiral amine catalysis | |
MacMillan-type iminium catalyst | 278173-23-2 | (5S)-(−)-2,2,3-Trimethyl-5-benzyl-4-imidazolidinone monohydrochloride | ≥97%, ≥98% (ee) | Chiral imidazolidinone salt that can be used for iminium activation of α,β-unsaturated aldehydes and studies of asymmetric conjugate addition | |
MacMillan-type iminium catalyst | 346440-54-8 | (2S,5S)-(−)-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone | ≥97% (GC) | Substituted imidazolidinone chiral amine catalyst that can be used for condition screening in conjugated acceptor activation, cycloaddition, and asymmetric addition | |
MacMillan-type iminium catalyst | 390766-89-9 | (2R,5R)-(+)-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone | ≥97% | Enantiomer of a substituted imidazolidinone; can be used to verify the role of catalyst configuration in controlling product enantioselectivity | |
MacMillan-type iminium catalyst | 323196-43-6 | (5R)-(+)-2,2,3-Trimethyl-5-benzyl-4-imidazolidinone monohydrochloride | ≥97% | Enantiomeric chiral imidazolidinone salt that can be used to compare product configuration reversal and mechanisms in iminium-catalyzed reactions | |
Chiral secondary amine silyl ether catalyst | 848821-61-4 | (S)-α,α-Bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrolidinemethanol trimethylsilyl ether | ≥97% | Silyl ether-protected prolinol catalyst that can be used in aldehyde enamine catalysis, iminium catalysis, and asymmetric addition reactions | |
Chiral secondary amine silyl ether catalyst | 943757-71-9 | (R)-(+)-α,α-Diphenyl-2-pyrrolidinemethanol trimethylsilyl ether | ≥96% | Enantiomer of diphenylprolinol silyl ether; can be used to compare the relationship between chiral amine catalyst configuration and product stereoselectivity | |
Chiral secondary amine silyl ether catalyst | 848821-58-9 | (S)-(−)-α,α-Diphenyl-2-pyrrolidinemethanol trimethylsilyl ether | ≥95% | Common chiral amine silyl ether catalyst that can be used in studies of aldehyde α-position activation, conjugate addition, and cascade reactions |
Table 3｜Chiral Brønsted Acid Catalysts
Category | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
BINOL-derived phosphoric acid Brønsted acid | 35193-63-6 | (±)-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate | ≥99% | Parent BINOL phosphoric acid structure that can be used in Brønsted acid catalysis, ion-pair activation, and structural comparison of chiral acid catalysts | |
Chiral BINOL-derived phosphoric acid catalyst | 791616-63-2 | (R)-3,3′-Bis(2,4,6-triisopropylphenyl)-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate | ≥98% | Bulky chiral phosphoric acid that can be used for imine activation, ion-pair control, and screening of asymmetric acid-catalyzed reactions | |
Chiral BINOL-derived phosphoric acid catalyst | 791616-62-1 | (R)-3,3′-Bis[3,5-bis(trifluoromethyl)phenyl]-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate | ≥98% | Electron-withdrawing aryl-substituted chiral phosphoric acid that can be used to tune acidity and the chiral pocket for activation of imine and acetal substrates | |
Chiral BINOL-derived phosphoric acid catalyst | 878111-17-2 | (S)-(+)-3,3′-Bis(3,5-bis(trifluoromethyl)phenyl)-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate | ≥98% | Enantiomer of an electron-withdrawing aryl-substituted chiral phosphoric acid; can be used to verify the chiral origin and product configuration in ion-pair catalysis | |
Chiral BINOL-derived phosphoric acid catalyst | 874948-63-7 | (S)-3,3′-Bis(2,4,6-triisopropylphenyl)-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate | ≥98% | Enantiomer of a bulky chiral phosphoric acid; can be used in studies of asymmetric addition, cyclization, and ion-pair-controlled reactions | |
Chiral BINOL-derived phosphoric acid catalyst | 35193-64-7 | (S)-(+)-1,1′-Binaphthyl-2,2′-diyl hydrogen phosphate | ≥97% | Basic chiral BINOL phosphoric acid structure that can be used in model Brønsted acid-catalyzed reactions and synthesis of chiral acid derivatives | |
Chiral BINOL-derived phosphoric acid catalyst | 361342-51-0 | (R)-3,3′-Bis(9-anthracenyl)-1,1′-binaphthyl-2,2′-diyl hydrogenphosphate | ≥95% | Anthracenyl-substituted bulky chiral phosphoric acid that can be used in acid-catalyzed asymmetric reactions requiring strict control of substrate approach direction |
Table 4｜Hydrogen-Bond Donor Catalysts and Bifunctional Thiourea Catalysts
Category | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Diaryl thiourea hydrogen-bond donor | 1060-92-0 | 1,3-Bis[3,5-bis(trifluoromethyl)phenyl]thiourea | ≥98% | Strong hydrogen-bond donor thiourea that can be used in studies of noncovalent activation of imines, nitroalkenes, and activated alkenes | |
Bifunctional thiourea catalyst | 851477-20-8 | 1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(1S,2S)-(+)-2-(dimethylamino)cyclohexyl]thiourea | ≥97% | Chiral thiourea–tertiary amine bifunctional catalyst that can provide both hydrogen-bond activation and a basic site; used in asymmetric addition reactions | |
Bifunctional thiourea catalyst | 620960-26-1 | 1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(1R,2R)-2-(dimethylamino)cyclohexyl]thiourea | ≥97% | Enantiomer of a chiral thiourea–tertiary amine bifunctional catalyst; can be used to compare the effect of catalyst configuration on asymmetric reaction outcomes | |
Monoaryl thiourea hydrogen-bond donor | 175277-17-5 | 1-(3,5-Bis(trifluoromethyl)phenyl)thiourea | ≥95% | Electron-withdrawing aryl thiourea structure that can be used in the synthesis of hydrogen-bond donor catalysts and studies of noncovalent activation systems | |
Cinchona alkaloid-derived bifunctional thiourea catalyst | 852913-25-8 | N-[3,5-Bis(trifluoromethyl)phenyl]-N′-[(9R)-6′-methoxy-9-cinchonanyl]thiourea | ≥90% | Cinchona alkaloid-derived thiourea catalyst containing both a chiral basic framework and hydrogen-bond donor site; used in studies of asymmetric nucleophilic addition |
Table 5｜N-Heterocyclic Carbene Precursors, Organic Bases, and Nucleophilic Catalysts
Category | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
N-heterocyclic carbene precursor | 67-03-8 | Thiamine hydrochloride | PharmPure™, USP | Thiazolium-type catalytic precursor that can be used in model studies of benzoin condensation and acyl anion equivalent reactions | |
Tertiary amine organic base/nucleophilic catalyst | 280-57-9 | Triethylene diamine (DABCO) | Moligand™, ≥98% | Bicyclic tertiary amine organic base that can be used for screening base catalysis, nucleophilic catalysis, and some addition reaction conditions | |
Strong organic base catalyst | 6674-22-2 | 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) | ≥99% | Non-nucleophilic strong organic base that can be used in deprotonation, elimination, addition, and organic base-catalyzed reaction systems | |
Acyl-transfer nucleophilic catalyst | 1122-58-3 | 4-Dimethylaminopyridine | ≥99% | Common acyl-transfer catalyst that can promote esterification, acylation, and carbonate formation; used in nucleophilic catalysis model studies | |
N-heterocyclic carbene precursor | 173035-10-4 | 1,3-Bis(2,4,6-trimethylphenyl)imidazolinium chloride | ≥98% | Imidazolinium salt-type carbene precursor that can be used to generate stable carbene active species and participate in umpolung and coupling reaction studies | |
Strong organic base catalyst | 5807-14-7 | 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (Hhpp) | ≥98% | Guanidine-type strong organic base that can be used in deprotonative activation, base-catalyzed addition, and polymerization-related reaction studies | |
N-heterocyclic carbene precursor | 4568-71-2 | 3-Benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride | ≥98% | Thiazolium salt-type carbene precursor that can be used in benzoin condensation, Stetter reactions, and acyl umpolung studies | |
N-heterocyclic carbene precursor | 250285-32-6 | 1,3-Bis(2,6-diisopropylphenyl)imidazolium chloride | ≥97% | Bulky imidazolium salt-type carbene precursor that can be used in carbene catalysis, coupling reactions, and umpolung systems |
Table 6｜Organic Nitroxyl Radicals and Hydrogen Atom Transfer Oxidation Catalysts
Category | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Nitroxyl radical oxidation catalyst | 2564-83-2 | TEMPO | Sublimed, ≥99% | Stable nitroxyl radical catalyst, commonly used with a terminal oxidant or co-oxidation system for selective alcohol oxidation, oxidation mechanism studies, and green oxidation condition development | |
Nitroxyl radical oxidation catalyst | 14691-89-5 | 4-Acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl free radical | ≥98% (GC) | Functionalized nitroxyl radical catalyst that can be used for alcohol oxidation, selective oxidation, and comparison of catalyst structural effects | |
Hydrogen atom transfer oxidation catalyst precursor | 524-38-9 | N-Hydroxyphthalimide | ≥98% | N-Hydroxyimide-type oxidative catalyst precursor that can participate in hydrogen atom transfer processes; used in hydrocarbon and benzylic oxidation studies | |
Nitroxyl radical oxidation catalyst | 7123-92-4 | KetoABNO | ≥95% | Bridged bicyclic nitroxyl radical catalyst, commonly used with a terminal oxidant or co-oxidation system for alcohol oxidation and screening of oxidation conditions for sterically hindered substrates |
Note: The products above are representative Aladdin products. For more product specifications, search by “product name/CAS/catalog number” on the Aladdin website.
References
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