1. In pharmaceuticals and fine chemicals, many molecules are chiral: the same molecular formula and connectivity may exist as two non-superimposable mirror-image forms (enantiomers). (With only one stereogenic center, there is usually one enantiomeric pair; with multiple stereocenters, multiple stereoisomers may exist, such as diastereomers, etc.) Biological systems are highly sensitive to chirality; therefore, the two enantiomers may differ markedly in efficacy, toxicity/side effects, metabolism, and systemic exposure. Regulators have long emphasized this as well: for example, the FDA’s 1992 guidance and relevant EMA guidance documents highlight the need for independent study of enantiomers/racemates and for robust chiral analytical methodologies.
2. This leads directly to a highly “engineering” practical problem: how can one obtain the target enantiomer reliably in a scalable, reproducible, and cost-controllable way? If the synthesis route cannot achieve high enantioselectivity in a single step, one must rely on feasible resolution/separation routes and dependable chiral analysis methods.
3. Cinchona alkaloids are repeatedly discussed because they offer an exceptionally scarce combination: a naturally available rigid chiral scaffold + modifiable functional positions + paired stereochemical variants. Together, these features turn “chiral control” into an actionable tool system, supporting both routes—making (asymmetric synthesis) and separating (resolution/enantioseparation).
2. Definitions: What are Cinchona alkaloids, and how do they relate to “alkaloids” and “chirality”?
2.1 The chemical definition of alkaloids
Key points in the IUPAC (Gold Book) definition of alkaloids are: basic nitrogen-containing compounds (often heterocycles), mainly of plant origin but not excluding animal sources. (Note: the Gold Book also states that amino acids, peptides, nucleotides, etc. are generally not classified as alkaloids.)
2.2 Definition of Cinchona alkaloids
Cinchona alkaloids are a class of natural alkaloids obtained from the bark of Cinchona species. They belong to the quinoline alkaloid family. Traditionally they are well known for antimalarial use; in modern chemistry, their more critical identity is as widely used chiral resources and derivatization platforms for stereoselective synthesis and enantiomer separation.
2.3 Four foundational terms
Term | Meaning | Relationship to Cinchona alkaloids |
Chirality | A molecule and its mirror image are non-superimposable | Establishes the real-world problem of “same molecule, different enantiomers” |
Enantiomers | A pair of mirror-image isomers | The goal is often one enantiomer; the other may produce different effects |
Racemate | A 1:1 mixture of two enantiomers | A common starting form; requires asymmetric synthesis or resolution/separation |
Enantiomeric excess (ee) | A common metric of enantiomeric purity | Used to evaluate “how clean” the chirality obtained is |
3. Classification framework: Four core parents × pseudoenantiomer switching × a map of tool families
First locate the scaffold by identifying “which parent core,” then determine the stereochemical direction via the “pseudoenantiomer pair,” and finally enter one of three tool families by application: PTC / AD ligands / recognition & separation.
3.1 Layer 1: Natural parent cores (the four most commonly used “core members”)
Reviews and the broader literature typically discuss the following four as the major/most commonly used Cinchona alkaloids. They are also the “parent nuclei” for most downstream catalysts and chiral separation materials.
Category | English name | Why it matters |
Major Cinchona alkaloids | Quinine | Frequently used as a chiral parent scaffold; readily derivatized into multiple families of chiral catalytic/recognition tools |
Major Cinchona alkaloids | Quinidine | Forms a stereochemical paired version with quinine; commonly used for “opposite enantioselectivity” switching |
Major Cinchona alkaloids | Cinchonine | Another widely used parent; paired with cinchonidine to provide an “opposite chirality” option |
Major Cinchona alkaloids | Cinchonidine | Forms a stereochemical paired version with cinchonine; facilitates platform screening and direction switching |
3.2 Layer 2: Pseudoenantiomer pairs — the key classification for switching enantioselectivity direction
In asymmetric synthesis, a very practical concern is: if one switches the chiral source to another member within the same family, can the direction of enantioselectivity be predictably inverted?
Therefore, the most commonly used and most operational grouping at the application level is to use the four parent cores as two pseudoenantiomer pairs (often for “direction switching/parallel controls”):
1. Quinine ↔ Quinidine
2. Cinchonine ↔ Cinchonidine
Note: some references pair them as QD/CN and QN/CD; the core meaning is the same—enabling switchable enantioselectivity direction within closely related platforms. (QN = Quinine, QD = Quinidine, CN = Cinchonine, CD = Cinchonidine)
In strict structural classification, these are mostly diastereomers rather than true mirror-image enantiomers; however, in catalysis and recognition contexts they are often called “pseudoenantiomers” because they commonly deliver opposite enantioselectivity directions on similar reaction platforms.
Pseudoenantiomer pair | Application-level meaning |
Quinine / Quinidine | Often used to switch a reaction’s selectivity from “favoring one enantiomer” to “favoring the other,” reducing the cost of searching for a completely new chiral source |
Cinchonine / Cinchonidine | Provides another switchable stereochemical set; often used for reaction-platform screening and enantiomer-direction control |
3.3 “From parent to tools”: three high-frequency derivative families
In practical R&D, Cinchona alkaloids are rarely used “as-is.” More commonly, functionalization is performed at modifiable sites to form tool families for different tasks. The table below lists the three most frequently encountered classes.
Tool family (by application) | Typical structural features | Which “chiral pain point” does it solve? |
Cinchona quaternary ammonium phase-transfer catalysts (PTC) | Quaternization at the nitrogen site to form controlled ion pairs/phase-transfer capability | Enables high enantioselectivity under biphasic/basic conditions; commonly used for constructing α-amino acid derivatives and related motifs |
Dimerized / ligand-engineered Cinchona derivatives (Sharpless AD ligand systems, etc.) | Stronger chiral environments via dimerization and ligand design | Uses mature ligand systems to achieve predictably switchable enantiomer direction (e.g., DHQ vs. DHQD systems) |
Bifunctional H-bond / basic-site organocatalysts (modified Cinchona scaffolds) | Introduction of (thio)urea and other H-bond donors on the Cinchona scaffold while retaining the amine site | “Substrate positioning + reactive-site activation” simultaneously, improving enantioselectivity and substrate scope |
4. Core mechanism: How does Cinchona prioritize the substrate into a single chiral pathway?
Chiral induction by Cinchona alkaloids (and their derivatives) can usually be compressed into three steps:
1. Capture: use noncovalent interactions (ion pairing/H-bonding, etc.) to “bind” the substrate onto the catalyst;
2. Orient: the rigid chiral scaffold fixes the substrate in an asymmetric pocket, generating facial selectivity/configurational selectivity;
3. Organize the reaction environment: in systems such as PTC (phase-transfer catalysis), further organize the reaction into controllable mass-transfer and interfacial channels via phase transfer/ion pairing.
4.1 Key functional modules in Cinchona chiral induction: a “basic combination set” classified by mechanism
Functional module | What it does in the system (mechanistic role) | Observable effects |
Rigid chiral scaffold (Cinchona scaffold) | Provides an asymmetric space and conformational constraints, orienting the “captured” substrate toward a single attack face/transition state | ee/er strongly depends on catalyst configuration; switching to the enantiomeric catalyst often inverts selectivity |
Nitrogen site: tertiary amine (protonatable) / derivatizable to quaternary ammonium | Tertiary amine: acts as a base/acceptor for activation and positioning; quaternary ammonium: forms ion pairs and enables phase transfer (PTC) | PTC: highly sensitive to water/biphasic systems/solid bases/anion identity; tertiary-amine systems: sensitive to acidity/basicity and H-bond–competitive solvents |
H-bond module: parent 9-OH / introduced (thio)urea, squaramide, etc. | An additional “second handle”: simultaneous positioning + activation (often bifunctional: H-bonds engage electronegative sites; the amine site tunes the nucleophile/anion) | Higher ee, broader substrate scope; sensitive to H-bond–competitive solvents/additives; common trend: more precise capture → more stable selectivity |
Side chain/aryl environment (often the key to going from “workable” to “excellent”) | By tuning pocket size and hydrophobic/π contacts around the catalyst, determines whether a substrate can “fit” and “sit correctly,” influencing substrate scope and the upper limit of ee (not always essential, but often decisive for broader compatibility) | The substrate scope changes most dramatically: with the same core, changing the side chain can cause large swings in ee/yield for certain substrates |
5. Three most common “deployment modes”: asymmetric catalysis, mature ligand methods, and enantiomer separation
Route | The task to solve (typical scenario) | Cinchona’s role (catalyst/ligand/stationary phase) | Direct benefits (why choose it) |
A. Asymmetric phase-transfer catalysis (PTC) | Build stereocenters under biphasic or strongly basic conditions; common in α-alkylation and amino-acid–scaffold platforms | Cinchona-derived quaternary ammonium salts as chiral PTC: “capture” anionic substrates/intermediates via ion pairing and impose chiral control during interfacial/mass-transfer processes | Engineering-friendly (biphasic/solid–liquid base compatible); organizes otherwise hard-to-control ionic reactions into a controllable chiral channel |
B. Mature ligand system: Sharpless asymmetric dihydroxylation (AD) | Construct vicinal diols with high enantioselectivity (very common intermediates; mature methodology) | Cinchona-derived ligands (DHQ/DHQD series and derivatives) with Os systems determine enantioselectivity direction; often used in an engineered AD-mix format | Switchable direction, mature platform, strong reproducibility; standardized conditions/formulations support scale-up and process development |
C. Chiral separation/analysis (CSP, etc.) | Synthesis cannot easily deliver high ee in one step, or QC/release is required: prove enantiomeric purity, separate enantiomers for downstream studies | Cinchona derivatives as chiral selectors/chiral stationary phases (CSP): enantiorecognition via ion pairing/H-bonding/π interactions; often advantageous for charged/zwitterionic analytes | No need to force the reaction to “ultimate ee” first: separate and quantify the two hands; serves as a process backstop and a QC tool |
6. Route-selection decision table: derive the next strategy from the starting conditions
Starting point (most common current situations) | Preferred route | Key criterion | Next critical actions |
The target needs a stereocenter, and the reaction can run under strong base and biphasic (or solid–liquid base) conditions | A. Asymmetric PTC | PTC often integrates “anionic substrate transfer + ion-pair orientation + chiral environment” into one catalytic cycle, making scale-up easier from the outset | Define substrate type (typically one forming a stable anion); select a Cinchona quaternary ammonium scaffold and counterion; troubleshoot common issues: emulsification/water-content drift, base strength and phase ratio, strong-coordination/strong H-bonding substrates causing ee loss, etc. |
The target is a vicinal diol fragment and you want a mature method with switchable direction and high reproducibility | B. Sharpless AD | Cinchona-ligand families (DHQ/DHQD) enable switchable enantioselectivity direction with highly standardized methodology | Choose the direction logic and substrate boundaries for AD-mix-α/β (or equivalent recipes); watch for side reactions (peroxidation/peroxide systems, over-oxidation, etc.) and the safety/compliance essentials of Os chemistry (toxicity, handling, waste disposal) |
You already have a racemate, or ee is unstable, but you must deliver a single enantiomer / provide an ee report | C. Chiral separation/analysis (CSP, etc.) | When synthesis is unstable, separation is often the fastest “delivery path,” while also meeting method development and QC/release needs | Judge suitability for Cinchona CSPs (ionizable/charged/zwitterionic systems often benefit); optimize mobile phase, ionic strength, and additive effects; establish method transferability and reproducibility (retention time, resolution, column-to-column consistency) |
7. Practical case: O’Donnell-type amino-acid alkylation—key “handles” and reproducibility points for Cinchona quaternary-ammonium PTC
1. Scenario
A chiral α-carbon center must be constructed, with the goal of obtaining a single enantiomer of an α-amino acid derivative (natural or non-natural amino-acid fragments fall into this category), commonly used in pharmaceutical intermediates and chiral building blocks.
2. Why choose this route
Classic studies show that under PTC (phase-transfer catalysis) conditions, Cinchona-alkaloid-derived chiral quaternary ammonium salts can organize deprotonatable substrates into a “chiral ion-pair channel,” enabling enantioselective alkylation under biphasic/basic conditions to build α-chiral amino-acid derivatives.
3. Key handles and reproducibility points in the case
Key step | What you are doing (the essential action) | Why enantioselectivity arises (the mechanistic handle) | Key control (no added complexity) |
1. Choose a “glycine imine/ester” type substrate | Convert the target α-position into a controllable “anionic equivalent” (a deprotonatable nucleophile precursor) | Selectivity is mainly decided at the bond-forming step involving the anion; the substrate platform determines whether a “controllable channel” can exist | First confirm that the substrate can stably generate the reactive species under the chosen base (no mechanism probing needed—just whether it can enter the reaction) |
2. Use a Cinchona-derived quaternary ammonium salt as chiral PTC | Form and carry an “anion–catalyst” ion pair in a biphasic/solid–liquid base environment | The chiral ion pair provides an asymmetric microenvironment that determines the nucleophile’s attack face; phase transfer confines effective reaction to a controllable channel | Run a “no catalyst or achiral phase-transfer salt” control: if the background reaction is already very fast, high ee is often hard to achieve |
3. Switch configuration direction using pseudoenantiomers | Replace the catalyst with a paired Cinchona stereochemical variant (use as a pair) | If the system is truly dominated by chiral ion pairing, the selectivity direction often switches with the catalyst stereochemical variant | Change only the catalyst stereochemical variant and keep everything else constant: check whether ee direction predictably inverts (tests whether a “chiral channel” is real) |
4. Use ee / yield / reproducibility as “delivery metrics” | Translate “understandable” into “doable and reproducible” | ee measures selectivity, yield measures usability, reproducibility measures whether the process window is stable | Fix temperature, stirring/phase ratio, and water control, then repeat: if ee/conversion still drifts, the channel is likely easily perturbed by phase behavior or salt effects |
8. Failure diagnosis & correction table: key-variable troubleshooting paths for the three routes (PTC / AD / chiral separation)
Route | Typical phenomenon (observable symptom) | Primary suspects (check 1–2 first) | Priority verification actions (no added complexity) | Correction direction |
PTC (Cinchona quaternary ammonium salts) | ee is very low or fluctuates strongly between batches | (1) Nonselective background pathway too strong (catalyst channel cannot “dominate”); (2) water/salt effects/phase behavior drift disrupts ion-pair organization | A) Compare “no catalyst or achiral PTC salt” to assess background strength; B) repeat with fixed temperature and stirring; C) switch pseudoenantiomer and see whether ee direction changes | First prove that “the ion-pair channel can dominate”: suppress background, stabilize water content and phase ratio, avoid salts/additives that disrupt ion-pair structure; verify direction switching with pseudoenantiomers |
PTC (Cinchona quaternary ammonium salts) | Conversion is slow or stalls | (1) Mass transfer/phase transfer insufficient (layering, poor mixing); (2) deprotonation insufficient (base strength or effective contact insufficient) | A) Increase mixing efficiency first (rule out mass transfer); B) before changing route, run “base strength/phase ratio” controls | Build a stable baseline of “mass transfer + deprotonation” first, then refine selectivity; for scale-up, treat stable phase behavior as a hard requirement |
PTC (Cinchona quaternary ammonium salts) | Emulsification; scale-up becomes uncontrollable | (1) Stirring shear/addition sequence induces stable emulsions; (2) salts/byproducts change interfacial tension | A) Run a stirring-intensity gradient; B) observe whether a persistent emulsion/turbid layer forms and resists phase separation | Prioritize “clean phase separation”: adjust stirring mode, phase ratio, and addition order; break emulsions before discussing ee (otherwise data are not comparable) |
Sharpless AD (AD-mix-α/β) | ee direction is wrong / opposite to expectation | (1) Incorrect mapping of α/β to ligand system; (2) substrate type outside the empirical model | A) First verify the ligand correspondence in AD-mix-α/β; B) run α vs β side-by-side on the same substrate and see whether ee direction flips | The first control knob for direction is the ligand set: align “label/ligand” first, then discuss substrate effects; if needed, return to a known benchmark substrate as a reference |
Sharpless AD (same) | Reaction is slow / many side reactions | (1) Reagents/reoxidation system deviates from the standard window (ratio, activity, solvent/temperature control) | A) Run a benchmark under standard AD-mix conditions; B) prioritize ruling out reagent deactivation and ratio errors | Pull the system back into the “standard reproducible window” first, then do limited tuning; clearly follow Os safety and waste-handling requirements |
Chiral separation (Cinchona-CSP, etc.) | Two enantiomers barely separate | (1) Ionic-interaction window not opened (additives/ionic strength mismatch); (2) stationary phase type mismatch | A) Screen directionally with a basic additive set (acid/base/salt); B) if needed, switch to a zwitterionic Cinchona CSP type | The key is matching “ionic state + additive window”; for ionizable/zwitterionic analytes, prioritize the corresponding CSP type and additive strategy |
Chiral separation (same) | Peak tailing / poor reproducibility | (1) Strong adsorption/secondary interactions; (2) additive concentration or sample solvent instability | A) Fix additive concentration and repeat; B) check compatibility between sample solvent and mobile phase | Stabilize peak shape first, then optimize resolution and quantitation; in method records, treat additives and ionic state as “must-be-traceable items” |
9. Product Navigation Table | Cinchona Alkaloid Chiral Control: Quickly Locate What You Need by Research Task (Tables A–D)
Research / experimental need | Recommended table to check first | Why start with this table | Representative products in the table |
Perform Cinchona-alkaloid–based chiral resolution / chiral recognition: screen first using readily available parent alkaloids or salts (and want the option to invert configuration) | Table A. Cinchona parent alkaloids and common salt forms | The first step in resolution/recognition is choosing the right chiral source: quinine/quinidine/cinchonine/cinchonidine and their salt forms determine basicity, solubility, ion pairing, and recognition mode. Even for the same parent, different salts (Cl⁻/SO₄²⁻, hydration state) can strongly impact reproducibility and the separation window. | (−)-Quinine, Quinidine, Cinchonine, Cinchonidine; Quinine sulfate dihydrate, Quinine hydrochloride dihydrate, Quinidine sulfate, Cinchonidine sulfate dihydrate |
Run a biphasic asymmetric reaction (nucleophile in aqueous phase/inorganic base, substrate in organic phase): need a chiral phase-transfer catalyst (PTC) to deliver ee | Table B. Chiral phase-transfer catalysts (PTC) | What you need is chiral ion-pairing and interfacial organization. For this type of problem, start with the quaternary-ammonium PTC family. Differences among Cinchona quaternary ammonium salts (cinchonine-type/quinuclidinium-type/quinine-type; anthracenylmethyl-enhanced variants) often affect substrate scope, rate, and ee more directly than changing solvent. | N-Benzylcinchoninium chloride; N-Benzylquinuclidinium chloride; N-Benzylquininium chloride; O-Allyl-N-(9-anthracenylmethyl) cinchoninium bromide |
Perform Sharpless asymmetric dihydroxylation (AD) / Os–Cinchona systems: the core is choosing the right dimeric/derivative ligand, with complementary configuration control | Table C. Chiral ligands and derivative building blocks (DHQ/DHQD and bridged dimers) | In AD/Os systems, enantioselectivity is primarily defined by the Cinchona dimeric ligand that “builds the chiral pocket.” If ee is insufficient, substrate fit is poor, or you need the opposite configuration, switching within the ligand family (AQN/pyrimidine/diazine-naphthalene bridges; DHQ vs DHQD) is usually more effective than fine-tuning temperature. | (DHQ)₂AQN; Dihydroquinidine (anthraquinone-1,4-diyl) diether; 2,5-Diphenyl-4,6-bis(dihydroquinine) pyrimidine; Dihydroquinine / dihydroquinidine (DHQ/DHQD) |
You don’t lack the chiral source, but the AD/Os system won’t run / is unstable / reproduces poorly: need to complete the set of co-oxidant, reoxidant, Os precursor, additives, solvent/base | Table D. General supporting reagents (building an AD/Os–Cinchona reaction system) | These issues often come from an unclosed catalytic cycle or mismatched mass-transfer/oxidative-regeneration conditions. Co-oxidant (NMO), reoxidant (K₃[Fe(CN)₆]), Os precursor (K₂OsO₄·2H₂O), additive (methanesulfonamide), and solvent system (t-BuOH/H₂O) determine whether active Os species can be generated stably and turnover sustained. | Potassium osmate(VI) dihydrate; Potassium ferricyanide; NMO (including monohydrate); Methanesulfonamide; tert-Butanol; Potassium carbonate |
Want to go from “parent → derivatization” and build a new PTC or new ligand (immobilization / linker introduction / structure–performance studies) | Table C (starting points & building blocks) + Table A (parent cores as controls) | Derivatization requires modifiable positions and stereochemical controls: functionalized quinuclidine-ring building blocks enable linkers/polymerizable sites; keeping parent/salt controls allows quick judgment of whether improvements come from true stereocontrol rather than solubility changes. | (1S,2R,5R)/(1S,2S,5S)-2-(Hydroxymethyl)-5-vinylquinuclidine; (−)-Quinine/Quinidine and their sulfate/hydrochloride salts |
Run system controls / method development: distinguish whether the issue is the chiral source (quinine/quinidine, etc.) or drift due to salt form/hydration/solubility | Mainly Table A (salt forms & parent cores); in parallel Table D (system conditions) if needed | Use Table A first to lock in chiral-source variables (same core with different salts; different cores as pseudoenantiomer pairs), then use Table D to lock in system variables (oxidative regeneration/solvent/base). This pinpoints whether ee drift or poor reproducibility comes from source vs. conditions. | Quinine sulfate dihydrate vs. quinine hydrochloride dihydrate vs. quinine sulfate hydrate; NMO/potassium ferricyanide/potassium osmate(VI) dihydrate/tert-butanol |
Do fluorescence analysis/standardization (quinine-related) while also wanting materials compatible with the “chiral control/catalysis” workflow | Table A. Parent cores & salt forms | Quinine salts (sulfate/hydrochloride) in Table A are commonly used in fluorescence analysis and method standardization; the same materials can also directly serve as Cinchona scaffold sources for chiral resolution/derivatization/catalysis controls—reducing workflow fragmentation. | Quinine hydrochloride dihydrate; Quinine sulfate dihydrate; Quinine sulfate hydrate; (−)-Quinine |
Table A | Cinchona Parent Alkaloids and Common Salt Forms (Quinine/Quinidine/Cinchonine/Cinchonidine and salts)
Category | CAS No. | Aladdin Cat. No. | Name | Specification / purity | Key features & applications |
Cinchona parent alkaloid | Quinine | 130-95-0 | (−)-Quinine | Moligand™, for resolution of racemates in synthesis | A classic Cinchona alkaloid: used as a chiral base and as a chiral recognition/resolution reagent; also a key parent core for building Cinchona-derived ligands and phase-transfer catalysts to create tunable chiral environments. | |
Cinchona parent alkaloid | Quinidine | 56-54-2 | Quinidine | Moligand™, ≥98%, contains 5–15% dihydroquinidine | A commonly used parent in the quinine pseudoenantiomer system: used to obtain the opposite product configuration (a “selectivity inversion” strategy); also an important starting point for DHQD-type dimeric ligands and quaternary-ammonium PTCs. | |
Cinchona parent alkaloid | Cinchonine | 118-10-5 | Cinchonine | ≥98% | One of the Cinchona parent alkaloids: can serve as a chiral base/resolving agent and a screening starting point; also commonly used to synthesize cinchonine-type quaternary-ammonium PTCs and other Cinchona-derived chiral catalysts. | |
Cinchona parent alkaloid | Cinchonidine | 485-71-2 | Cinchonidine | Moligand™, ≥98% | A widely used Cinchona chiral base: applicable to chiral resolution/recognition and catalyst screening; the scaffold can also be quaternized to form cinchonidine-type chiral phase-transfer catalysts. | |
Cinchona alkaloid salt | Quinine salt | fluorescence/analysis & chiral source | 6119-47-7 | Quinine hydrochloride dihydrate | For fluorescence analysis, ≥99% | Quinine hydrochloride: a common fluorescence-analysis/method standard; in Cinchona chiral-control contexts, it can also serve as a quinine source (convenient weighing/solubility) for preparing/benchmarking Cinchona-derived catalysts or chiral resolution systems. | |
Cinchona alkaloid salt | Quinine sulfate | fluorescence/analysis & chiral source | 6119-70-6 | Quinine sulfate dihydrate | BioReagent, for fluorescence analysis, Moligand™, ≥99% | A classic fluorescence reference (widely used in analysis/methodology); in chiral-control workflows, provides a high-purity quinine salt source for preparing Cinchona-derived catalysts or serving as a “quinine-system” control. | |
Cinchona alkaloid salt | Quinine sulfate | salt-form control | 207671-44-1 | Quinine sulfate hydrate | ≥99% | Salt-form control (hydrate): used to compare how salt identity (Cl⁻ vs SO₄²⁻) and hydration state affect solubility, ion pairing, and catalytic/resolution performance—supporting reproducibility in chiral systems. | |
Cinchona alkaloid salt | Quinidine sulfate | 6591-63-5 | Quinidine sulfate | ≥98% | Quinidine salt source: convenient for dissolution/weighing and establishing “quinidine-system” controls (paired comparisons with quinine salts); used for resolution, chiral recognition, or derivative ligand/catalyst synthesis. | |
Cinchona alkaloid salt | Cinchonidine sulfate | 524-61-8 | Cinchonidine sulfate dihydrate | ≥98% | Cinchonidine salt form: used to compare free base vs. salt, and the impact of counterion/hydration on chiral induction and reproducibility; also serves as a feedstock for further derivatization (e.g., quaternization). | |
Cinchona alkaloid salt | Quinidine hydrochloride | 6151-40-2 | Quinidine hydrochloride monohydrate | ≥95% | Quinidine hydrochloride: a stable salt source for “quinidine-system” controls (easy weighing/solubility); used in chiral resolution/recognition, catalyst screening, or as a starting material for Cinchona-derived catalyst synthesis. | |
Cinchona derivative/salt | weak cinchona base salt | system control | 5949-16-6 | Weak cinchona base sulfate dihydrate | ≥98% | A Cinchona-base-related salt control: used to compare how “basicity strength/salt form/hydration” influence chiral recognition, resolution efficiency, or catalytic performance—helpful for determining whether chirality originates from the Cinchona scaffold itself. |
Table B | Chiral Phase-Transfer Catalysts (PTC): Cinchona Quaternary-Ammonium Salt Family
Category | CAS No. | Aladdin Cat. No. | Name | Specification / purity | Key features & applications |
Chiral PTC | Cinchona quaternary ammonium | cinchonine-type | 69221-14-3 | N-Benzylcinchoninium chloride [chiral phase-transfer catalyst] | ≥99% | A typical Cinchona quaternary-ammonium PTC: organizes nucleophiles and substrates at the biphasic interface via ion pairing/H-bonding and other multipoint interactions, enabling asymmetric alkylation, Michael addition, epoxidation/thioetherification, and other common enantioselective transformations. | |
Chiral PTC | Cinchona quaternary ammonium | quinuclidinium-type | 77481-82-4 | N-Benzylquinuclidinium chloride [chiral phase-transfer catalyst] | ≥98% | A typical Cinchona-derived quaternary-ammonium PTC (quinuclidinium-type): offers stronger ion-pair organization and tunable substituents for multiple biphasic asymmetric transformations (often used for rapid enantioselectivity screening). | |
Chiral PTC | Cinchona quaternary ammonium | cinchonidinium-type | 69257-04-1 | N-Benzylcinchonidinium chloride | ≥98% | A cinchonidinium-type Cinchona quaternary-ammonium salt: a member of the PTC family associated with the cinchonine/cinchonidine scaffold, commonly used to benchmark how parent-core choice (Q/D/CN/CD) impacts ee, rate, and substrate scope. | |
Chiral PTC | Cinchona quaternary ammonium | quinine-type | 67174-25-8 | N-Benzylquininium chloride [chiral phase-transfer catalyst] | ≥95% | A quinine-scaffold quaternary-ammonium PTC: transfers chirality through ion pairing and multipoint weak interactions in biphasic systems; commonly used in asymmetric alkylation/addition reactions; suitable for parallel screening against quinuclidinium/cinchonine-type variants. | |
Chiral PTC | Cinchona quaternary ammonium | anthracenylmethyl-enhanced | 200132-54-3 | O-Allyl-N-(9-anthracenylmethyl) cinchoninium bromide | ≥95% | Anthracenylmethyl substitution can strengthen hydrophobic/π interactions and ion-pair organization: often used to improve enantioselectivity and substrate compatibility in PTC systems (especially for aromatic substrates or when stronger “chiral ion-pair” organization is needed). |
Table C | Chiral Ligands and Derivative Building Blocks: DHQ/DHQD Starting Points + Bridged Dimeric Ligands + Functionalized Scaffolds
Category | CAS No. | Aladdin Cat. No. | Name | Specification / purity | Key features & applications |
Cinchona derivative | Dihydroquinine (DHQ) | 522-66-7 | Dihydroquinine | ≥95% (HPLC), sum of enantiomers | DHQ is one of the commonly used “chiral parent” cores in Sharpless AD and related systems; more often used as a synthetic starting point for dimeric ligands and quaternary-ammonium PTCs to build stable, tunable chiral induction environments. | |
Cinchona derivative | Dihydroquinidine (DHQD) | 1435-55-8 | Dihydroquinidine | ≥95% | DHQD is the enantioselectivity-complementary parent to DHQ: used to access the opposite product stereochemistry or paired with DHQ for mechanistic/selectivity verification; a key precursor to dimeric ligands and quaternary-ammonium PTCs. | |
Cinchona scaffold building block | functionalized quinuclidine ring | 207129-36-0 | (1S,2R,5R)-2-(Hydroxymethyl)-5-vinylquinuclidine | ≥97% | A functionalized quinuclidine-ring building block: commonly used for directed modification of the Cinchona scaffold (introducing polymerizable/linkable sites) to develop new immobilized ligands, recyclable PTCs, or structure–performance relationship studies. | |
Cinchona scaffold building block | functionalized quinuclidine ring | 207129-35-9 | (1S,2S,5S)-2-(Hydroxymethyl)-5-vinylquinuclidine | ≥97% | A configurational control counterpart to the previous building block: used to compare how configuration differences affect chirality transfer in downstream ligand/catalyst derivatives, supporting configuration–ee mapping and mechanistic validation. | |
Chiral ligand | AQN-bridged dimer | (DHQ)₂AQN | 176097-24-8 | (DHQ)₂AQN | ≥95% | A classic Cinchona dimeric ligand: commonly paired with Os systems for asymmetric dihydroxylation; the AQN bridge pre-organizes the substrate in a chiral environment to deliver high ee (often used for methodology and substrate-scope screening). | |
Chiral ligand | AQN-bridged dimer | DHQD derivative | 176298-44-5 | Dihydroquinidine (anthraquinone-1,4-diyl) diether | ≥98% | A member of the Cinchona dimeric ligand family (anthraquinone-1,4-diyl bridge): often used in Os-catalyzed asymmetric dihydroxylation and related reactions; the bridged aromatic unit helps pre-organize the chiral environment, improving ee/selectivity for certain substrates. | |
Chiral ligand | pyrimidine-bridged dimer | DHQ derivative | 149820-65-5 | 2,5-Diphenyl-4,6-bis(dihydroquinine) pyrimidine | ≥97% | A pyrimidine-bridged Cinchona dimeric ligand family: enhances rigidity and pre-organization of the chiral pocket; commonly used in Os/Cinchona asymmetric dihydroxylation to increase ee and substrate compatibility. | |
Chiral ligand | pyrimidine-bridged dimer | DHQ derivative (dimethyl ether) | 149725-81-5 | Dihydroquinine 2,5-diphenyl-4,6-pyrimidine dimethyl ether | ≥97% | A methyl-ether derivative of pyrimidine-bridged dimeric ligands: used to tune solubility, sterics, and ion-pair interaction strength, thereby fine-adjusting ee and chemoselectivity in Os-catalyzed asymmetric dihydroxylation and related reactions. | |
Chiral ligand | diazanaphthalene-bridged dimer | DHQ derivative | 140924-50-1 | Dihydroquinine 1,4-(2,3-diazaphthalene) diether | ≥95% | A Cinchona dimeric ligand (2,3-diazaphthalene bridge): commonly used for Os-catalyzed asymmetric dihydroxylation; bridge rigidity plus tunable electronic/steric effects support high ee and often help build a “ligand selection map.” | |
Chiral ligand | diazanaphthalene-bridged dimer | DHQD derivative | 140853-10-7 | Dihydroquinidine 1,4-(2,3-diazaphthalene) diether | ≥95% | A pseudoenantiomeric counterpart to the DHQ-bridged diether above: commonly used to deliver the opposite configuration in Os-catalyzed asymmetric dihydroxylation, improving route generality via ligand choice aligned to target stereochemistry. |
Table D | General Supporting Reagents (Common “System-Building” Reagents for Sharpless AD / Os–Cinchona Systems)
Category | CAS No. | Aladdin Cat. No. | Name | Specification / purity | Key features & applications |
General reagent | AD/PTC support | inorganic base | 584-08-7 | P485463 | Potassium carbonate | Anhydrous grade, high purity, reagent grade, ≥99% | A common base/buffering base in Sharpless AD (AD-mix): used with K₃[Fe(CN)₆], K₂OsO₄, MeSO₂NH₂, etc. to maintain the reaction window; also frequently used as a mild inorganic base in Cinchona quaternary-ammonium PTC reactions. |
General reagent | AD support | solvent | 75-65-0 | tert-Butanol | Anhydrous grade, ≥99.5% | A common organic-phase solvent in AD systems (classic t-BuOH/H₂O combination): improves substrate solubility and mass transfer; works with Cinchona dimeric ligands/Os systems for asymmetric dihydroxylation; also used as a solvent-screening control under PTC conditions. | |
General reagent | AD support | reoxidant | 13746-66-2 | Potassium ferricyanide(III) | Ph.Eur, suitable for analysis, ACS, AR grade | A key reoxidant in Sharpless AD-mix: regenerates higher-valent Os species in Os-catalyzed asymmetric dihydroxylation; with (DHQ)/(DHQD) Cinchona dimeric ligands it sustains catalytic turnover and enantioselectivity. | |
General reagent | AD support | Os precursor | 10022-66-9 | Potassium osmate(VI) dihydrate | ≥99% | A common precursor for Os-catalyzed asymmetric dihydroxylation: generates active Os species under NMO/ferricyanide reoxidation systems and delivers enantioselective dihydroxylation of alkenes under Cinchona dimeric ligand control. | |
General reagent | AD-mix additive | 3144-09-0 | Methanesulfonamide | ≥98% (N) | A common AD-mix additive: helps improve rate/selectivity and control side reactions (typical for Os–Cinchona ligand systems), broadening substrate applicability and improving reproducibility. | |
General reagent | Os co-oxidant | 70187-32-5 | 4-Methylmorpholine N-oxide monohydrate | ≥98% | NMO·H₂O is a common co-oxidant in Os catalysis (including Cinchona dimeric ligand systems): reoxidizes lower-valent Os to the active state; frequently used for setting up and benchmarking asymmetric dihydroxylation and related oxidative transformations. | |
General reagent | Os co-oxidant | 7529-22-8 | 4-Methylmorpholine N-oxide (NMO) | ≥97% | NMO (anhydrous/low-water versions for water-controlled systems): serves as a co-oxidant in Os–Cinchona ligand catalysis to regenerate active Os species; used to evaluate how water content affects rate and selectivity. |
Note: The above are representative Aladdin products. For additional specifications, please refer to the product list at the end of the article, or search the Aladdin website using the “product name / CAS / catalog number.”
Aladdin: https://www.aladdinsci.com/
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