1.What are “organozinc reagents” for synthesis?
1.1 Definition
Organozinc reagents (organozinc reagents) typically refer to a class of organometallic reagents used in organic synthesis as carbon-group donors / transfer agents. Their shared hallmark is the presence of a carbon–zinc (C–Zn) bond. In practical terms, they can “deliver” an organic group R to a reaction system in a relatively controllable manner—most commonly to form new C–C bonds (the classic use), and in certain systems also to form C–X bonds or enable specific addition/functionalization transformations.
From a structural classification standpoint, organozinc compounds belong to the broader family of organometallic compounds (defined by a bond between a metal and an organic carbon). The term “organozinc reagents for synthesis” emphasizes their role as operational, usable reagents in synthetic transformations: on one hand, the C–Zn bond is relatively mild, often offering better functional-group compatibility than Grignard reagents or organolithiums; on the other hand, many organozinc reagents remain sensitive to water/oxygen and acidic protons, requiring dry/inert handling or being generated in situ and used promptly.
Three practical criteria (“tests”):
- Structural criterion: the system contains a reactive C–Zn bond (or an organozinc species that dominates the observed reactivity).
- Functional criterion: the species primarily serves as an R-group transfer agent (e.g., nucleophilic addition, transmetalation into a cross-coupling cycle) to form bonds.
- Form criterion: it often exists as solutions / complexes / aggregates, with reactivity strongly modulated by solvent, halides, and added salts (e.g., LiCl). Therefore, the “formulation/conditions” are frequently a key part of reproducibility.
1.2 What are the most common “working forms” in practice?
In research and process settings, the most common forms include:
- RZnX (organozinc halides; heteroleptic organozinc): R = alkyl/aryl/alkenyl, etc.; X is typically Cl/Br/I.
- R₂Zn (diorganozinc): two organic groups are bound to Zn.
- Organozincates (zincates; “ate” complexes): in the presence of LiX (especially LiCl) or abundant halide, RZnX often exists as species such as Li⁺[RZnX₂]⁻, and may form higher-order zincates. These species are frequently discussed as being strongly linked to transmetalation efficiency and reproducibility.
1.3 Common points of confusion
1.3.1 Do “Reformatsky reagents” generated in situ count as organozinc reagents?
Yes—and they are among the most classic and widely used on-demand, in situ generated organozinc reagents.
- In the Reformatsky reaction, an α-halo ester (more broadly, an α-halo carbonyl compound) undergoes insertion/oxidative addition with metallic zinc, generating a zinc enolate in situ—often called a Reformatsky reagent / Reformatsky enolate.
- It is an organozinc species: the key feature is not a “free enolate anion,” but rather a Zn-coordinated/stabilized nucleophilic carbon center (often in a dynamic equilibrium among coordinated and aggregated states). This species then adds nucleophilically to aldehydes/ketones to form a zinc alkoxide intermediate, which upon acidic workup affords a β-hydroxy ester (or the corresponding β-hydroxy carbonyl compound).
1.3.2 Why doesn’t it usually “attack the ester carbonyl”?
- Under typical Reformatsky conditions, the Reformatsky zinc enolate is less basic and more moderate in nucleophilicity than lithium enolates or Grignard reagents; meanwhile, ester carbonyls are intrinsically less reactive toward nucleophilic addition than aldehydes/ketones. Therefore, the usual selectivity is: addition to aldehydes/ketones is faster, while competitive addition to the ester carbonyl of the α-halo ester itself (and to ordinary ester carbonyls present) is typically not significant.
- Importantly, “doesn’t” should be understood as “does not meaningfully compete under standard conditions,” not as “absolutely impossible.” Side pathways can still emerge under strong activation, special substrates, or special conditions.
2.Research context: Why do organozinc reagents have unique value in drug discovery and process development?
2.1 Context 1: C–C bond construction is the core “output action” in API routes
- In many API/fine-chemical routes, the step that truly sets the ceiling for complexity and yield is often the key C–C bond-forming step. To reliably progress in the presence of complex functional groups, heterocycles, and sensitive motifs, chemists must choose among different organometallic options.
- An empirical ordering of “aggressiveness” (basicity/nucleophilicity) is often:RLi (strongest, “hardest,” most side reactions) > RMgX (strong) > RZnX (milder, more controllable).
- This is not to say “weaker is always better,” but rather that organozinc reagents more readily steer a reaction toward selectively forming the target bond, instead of pulling every electrophile and acidic proton in the system into side reactions.
2.2 Context 2: Negishi coupling made “organozinc” a key partner in cross-coupling
- One of the most emblematic industrial/medicinal applications of organozinc reagents is Negishi coupling (Pd- or Ni-catalyzed cross-coupling), which uses organozinc partners to form C–C bonds. The 2010 Nobel Prize in Chemistry introduction explicitly highlights that Negishi developed a zinc-based cross-coupling variant in 1977 (i.e., the Negishi reaction).
- In cross-coupling, organozinc reagents are often viewed as an optimal compromise between reactivity and functional-group tolerance: they are typically reactive enough to undergo transmetalation and enter Pd/Ni catalytic cycles, yet often provide a broader compatibility window than organolithium/Grignard systems—supporting stable progress with complex substrates.
2.3 Context 3: The main barrier is often “usability/operability,” not the reaction itself
1. Many organozinc reagents are sensitive to water/oxygen and acidic protons; meanwhile, the reagent-generation step (Zn insertion/exchange/transmetalation) can be exothermic and strongly dependent on zinc surface state and activation, leading to hard-to-control concentrations, batch variability, and reproducibility risks—key concerns in both labs and scale-up.
2. Accordingly, improvement strategies aimed at “more stable, easier-to-weigh/transfer, more reproducible” organozinc workflows have remained active in recent years:
- OPiv (pivalate)-supported solid organozinc reagents: early foundational work (2013/2014) demonstrated that aryl/heteroaryl zinc pivalates can be relatively air-tolerant solids with broad applicability; more recent reviews (e.g., 2022/2024) systematically summarize preparation and applications, emphasizing how salts/counterions and preparation routes influence stability and reactivity.
- Expansion from aryl/heteroaryl to the more challenging “alkyl organozinc” stabilization: for example, salt-stabilized solid alkyl zinc pivalates reported in 2023 illustrate that “operability upgrades” are extending to broader substrate classes.
- On-demand generation, continuous flow, and automated workflows: coupling “generation → use” in one process (e.g., for Negishi coupling) can markedly improve usability and reproducibility for unstable organozinc reagents—especially friendly to scale-up and high-throughput experimentation.
3.Structural basis: Why are organozinc reagents “milder and more controllable”?
Structural/Chemical Feature | Explanation (Why it matters) | Impact on Rate / Selectivity / Reproducibility |
The C–Zn bond is typically more covalent and less strongly polarized (weaker ionic character than C–Li/C–Mg) | The “negative character” on carbon is more dispersed; overall basicity/nucleophilicity is usually lower (a “softer” carbon nucleophile) | Often gives milder nucleophilicity and better functional-group tolerance; in cross-coupling, selectivity is more easily maintained under complex-substrate conditions |
Zn coordination environment and aggregation are highly tunable: R₂Zn is often near-linear, 2-coordinate; RZnX/salt-containing systems often show 3–4 coordination and may form aggregates or “ate” complexes | Zn(II) is a Lewis-acidic center that readily coordinates solvents, halides, and added salts; solutions are often dynamic multi-species equilibria rather than a single structure | Solvent, salts (e.g., LiCl), and halide concentration can strongly shift active-species distributions and transmetalation efficiency, thereby affecting rate, selectivity, and reproducibility |
Solution behavior differs substantially between R₂Zn and RZnX (halides/ligating solvents change aggregation and polarity) | RZnX more readily forms coordinated/aggregated structures and is more condition-dependent; R₂Zn can be a “cleaner” organozinc center but may be more system-sensitive | RZnX is more commonly used in coupling/transmetalation; R₂Zn is more often used in specific additions or specialized transmetalation contexts (chosen based on project needs) |
Organozincate (“ate”) species may form (often discussed when halides/added salts are abundant) | “Ate” complexes are frequently considered relevant to key transmetalation steps in certain systems; the true active species may differ from the nominal formulation | For some couplings, transmetalation rate, selectivity, and batch-to-batch reproducibility may hinge on this variable (especially in systems with strong salt effects) |
Sensitive to water/oxygen/acidic protons; easily quenched (sensitivity depends on system) | The “engineering barrier” often lies in preparation, storage, transfer, and consistency of concentration/activity | Drives the development of more stable solid organozinc reagents (e.g., OPiv-supported), on-demand generation, and continuous/automated operability strategies |
4.Application scenarios: What “key reaction tasks” use organozinc chemistry?
Application Type | Representative Reaction | Role of Organozinc | Key Point |
Carbonyl addition: mild C–C formation | Reformatsky reaction | α-halo ester + Zn generates a Reformatsky enolate (an organozinc species) that adds to aldehydes/ketones | Because it is milder, it typically does not attack esters (more restrained than strong enolates/Grignards) |
Cross-coupling: handing R to Pd/Ni | Negishi coupling | Organozinc reagent acts as the coupling partner and participates in transmetalation | A Nobel-recognized cross-coupling family; often advantageous for complex substrates |
Improving operability: making reagents more “user-friendly” | More air/moisture-stable solid organozinc reagents (e.g., pivalates) | Stability is enhanced via ligand/anion design for easier weighing/transfer | Addresses the “too sensitive, hard to use” pain point and broadens routine lab/process adoption |
Activation and generation-end mechanisms | Activator/surface-activation studies | Improves Zn insertion/generation efficiency and reproducibility | A major “engineering challenge” in organozinc chemistry: not just the reaction equation, but controllable generation processes |
5.Master classification table of organozinc reagents for synthesis
Major Class | Common Notation | Core Features | Typical Use / Positioning |
Organozinc halides (heteroleptic) | RZnX (often as aggregates/complexes, e.g., coordinated with solvent/salts) | The most common and most general class; aggregation and reactivity are strongly influenced by solvent, halides, and salt effects (e.g., LiCl) | A general starting point for Negishi and many transformations; the “workhorse type” for transmetalation/coupling condition development |
Diorganozinc | R₂Zn | No halide X; reaction pathways are more “customized”; often more reactive and more sensitive (higher demands on operation and safety) | Specialized organozinc sources for project-driven systems: certain additions/transmetalations/carbene-related chemistry (e.g., Simmons–Smith) |
Organozincates (zincate, “ate”) | e.g., R₂ZnX⁻, RZnX₂⁻, R₃Zn⁻ (paired with Li⁺/MgX⁺, etc.) | Anionic “ate” species, often in strong-base / excess organometallic or specific salt environments; may represent the true reactive form in some systems | Influences transmetalation, rate, and selectivity; frequently discussed in mechanism and difficult-substrate coupling optimization |
Reformatsky-type zinc reagents | “Reformatsky zinc enolate” (from α-halo carbonyl + Zn) | Essentially α-substituted organozinc / zinc enolate complexes (often coordinated/aggregated), enabling controlled carbonyl addition under mild conditions | Mild carbonyl additions and classic C–C construction; a functional-group-tolerant entry to “Zn-mediated additions” |
Stabilized / easy-to-handle solid organozinc reagents (operability dimension) | e.g., organozinc carboxylates (pivalates, etc.) / coordination-stabilized derivatives | Operability-driven (solid, easy to weigh/transfer, more batch-friendly); still requires water/oxygen protection (usually only relatively more stable) | Lowers the barrier to organozinc adoption in routine labs and process scale-up (especially when reproducible metering is needed) |
6.Product Selection Navigation Table | Organozinc-reagent-related: Quickly locate Tables 1–4 by research task
Need / Scenario | First Table to Check | Why this table is the best fit | Representative products in the table |
Generating/preparing organozinc reagents from scratch (halide insertion, Reformatsky, etc.), or the reaction won’t start / is very slow and needs troubleshooting | Table 1 | Core zinc system: Zn source / Zn salts / organozinc reagents + key activation and salt effects | The key variables for organozinc formation cluster around zinc form, zinc salts, activators, and salt effects; solve “can it be generated reproducibly, and is activity controllable” first |
Planning a Negishi cross-coupling and needing to choose catalyst/ligand systems (Pd vs Ni; PPh₃ vs bisphosphines; whether to run ligand screening) | Table 3 | Cross-coupling catalysts and ligands (Pd/Ni + phosphine ligands) | Success/failure is often determined by the catalyst precursor + ligand combination; this table consolidates “proven starter sets” and general sources for screening |
Substrate/condition screening: selecting a “benchmark electrophile panel” to map the reaction window (aryl/benzyl/heteroaryl/allyl) and probe electronic effects / coordination inhibition | Table 4 | Representative electrophiles + condition control/quench + titration/standardization kit | The most efficient approach is to scan a representative electrophile panel quickly; also keep common quench/additives in the same kit |
Reformatsky / α-functionalization (α-bromo esters, α-bromo nitriles, acyl chlorides): comparing sterics/ester types on Zn insertion and downstream reactivity | Table 4 | Representative electrophiles + condition control/quench + titration/standardization kit | The core “comparability” in Reformatsky/insertion workflows comes from the substrate set (ester type, sterics, functional groups) |
System is very sensitive / poor reproducibility: suspect water/oxygen/solvent grade; need appropriate reaction solvent and backup solvent systems | Table 2 | Reaction & workup media: solvents (ethers / aromatics / polar aprotics / analytical solvents) | Organozinc systems are extremely sensitive to solvent water content, stabilizers, and coordinating ability; a wrong solvent choice can directly cause deactivation/side reactions/non-reproducibility |
Workup/quench/phase separation/washing/solvent swap: avoiding over-quenching or introducing side reactions | Table 2 | Reaction & workup media (solvents) + Table 4 (quench salts/acids) | Common workup issues include decomplexation, difficult phase separation, and residual metal salts; these tables combine common workup media with mild quench additives |
Standardization / activity assessment of organozinc reagents (e.g., batch variability; want effective concentration/activity) | Table 4 | Representative electrophiles + condition control/quench + titration/standardization kit (iodometric titration chain) | This table consolidates the core iodometric titration reagent chain for common SOP-style standardization and reduces missing components |
Difficult substrates or low conversion: considering ZnBr₂/ZnCl₂ as Lewis acid / salt effect, or using LiCl to improve solubility and reactivity | Table 1 | Core zinc system: Zn source / Zn salts / organozinc reagents + key activation and salt effects | These “add one variable and it gets better/worse” effects often concentrate in zinc salts and salt effects; suitable for systematic controls |
Table 1 | Core Zinc System: Zinc Sources / Zinc Salts / Organozinc Reagents + Key Activation & Salt Effects
Category | CAS No. | Aladdin Cat. No. | Name | Grade / Purity | Uses & Selection Notes (Organozinc Reagents for Synthesis) |
Zinc source (metallic zinc) | 7440-66-6 | Z112688 | Zinc powder | PrimorTrace™, ≥99.99% metals basis, powder, 600 mesh | A metallic zinc source for preparing organozinc reagents: 600-mesh zinc powder has high surface area and typically initiates more readily. Commonly used for halide insertion to form RZnX and for generating Reformatsky-type zinc reagents, helping improve reaction rate and reproducibility. Recommended to pair with standard activation/initiator strategies (I₂, 1,2-dibromoethane, TMSCl, etc.) and to maintain strictly anhydrous, deoxygenated conditions. Finer zinc powder is more reactive; the risks of exotherms, side reactions, and (in extreme cases) pyrophoric behavior are higher—tight temperature control, portionwise addition, and compliant safety management are required (regulated hazardous material). |
Zinc source / zinc salt (Lewis acid / additive) | 7646-85-7 | Zinc chloride | AR, ≥98% | A commonly used Zn(II) salt and Lewis-acid additive. Useful for building/tuning zinc-containing systems (e.g., substrate activation, complex formation, promoting salt effects in certain addition/coupling systems). | |
Zinc source / zinc salt (ultra-dry / trace-metal grade) | 7699-45-8 | Zinc bromide | PrimorTrace™, ultra-dry grade, ≥99.99% metals basis | High-purity, ultra-dry ZnBr₂ for systems sensitive to trace metals or requiring stringent moisture control in zinc-salt conditions. Also used as a Lewis acid / salt-effect additive. | |
Salt effect / complexation promoter (LiCl) | 7447-41-8 | Lithium chloride | Anhydrous, 99.99% metals basis | Classic LiCl salt effect: under Knochel-type conditions, often used to promote formation/stabilization of more soluble RZnX·LiCl complex systems, improving solubility, mass transfer, and reactivity of organozinc intermediates. Frequently applied in organozinc generation and in optimizing difficult-substrate conditions for Negishi coupling. | |
Activation / water-scavenging additive (chlorosilane) | 75-77-4 | Trimethylchlorosilane (TMSCl) | For GC derivatization, ≥99% (GC) | Commonly used as an additive for activating metallic zinc surfaces / promoting insertion (reacts with oxide layers / trace water to improve initiation), and frequently appears in organozinc generation/promoting systems. Also serves as a water/alcohol scavenger. | |
Activator / initiator (zinc powder activation) | 106-93-4 | D104774 | 1,2-Dibromoethane | ≥99% | A classic initiator/activator for zinc powder: reacts with Zn to generate ZnBr₂ and clean the surface, helping halide insertion start faster—useful in troubleshooting “reaction does not start.” |
Organozinc reagent (neat reagent) | 557-20-0 | Diethylzinc | Packaging for deposition systems | A highly reactive organozinc reagent: used in Simmons–Smith chemistry (forms zinc carbenoid with CH₂I₂), as a transmetalation/coupling precursor, or as an organozinc source. Requires strictly inert, anhydrous handling. | |
Organozinc reagent (solution) | 544-97-8 | D140708 | Dimethylzinc | 1.0 M in toluene | A highly reactive methylation/transmetalation organozinc reagent. Supplied as a solution for easier metering and controlled addition; used for coupling/transmetalation, etc. (strictly inert atmosphere; observe enhanced safety precautions). |
Organozinc reagent (neat reagent) | 1078-58-6 | Diphenylzinc | ≥99% | An aryl organozinc reagent for aryl transmetalation/coupling or as a source of aryl nucleophile equivalents. Relatively sensitive; requires inert, anhydrous conditions. |
Table 2 | Reaction & Workup Media: Solvents (Ethers / Aromatics / Polar Aprotic / Analytical Solvents)
Category | CAS No. | Aladdin Cat. No. | Name | Grade / Purity | Uses & Selection Notes (Organozinc Reagents for Synthesis) |
Key solvent (ether) | 109-99-9 | T431417 | Tetrahydrofuran (THF) | For DNA & peptide synthesis (max 0.005% H₂O) | One of the most commonly used solvents for organozinc generation and Negishi coupling; favorable for salt dissolution and mass transfer. Strict drying/deoxygenation is critical to organozinc stability and reproducibility. |
Key solvent (ether) | 110-71-4 | 1,2-Dimethoxyethane (DME) | Anhydrous, ≥99.5%, inhibitor-free | A strongly coordinating ether solvent that supports salt dissolution and mass transfer; commonly used in organozinc generation/transmetalation and coupling systems (also requires rigorous deoxygenation and drying). | |
Key solvent (greener ether alternative) | 96-47-9 | 2-Methyltetrahydrofuran (2-MeTHF) | Anhydrous, ≥99%, no stabilizer | A common alternative to THF (often considered “greener” and more hydrophobic). Can be used for organozinc generation/coupling and process scale-up exploration (still requires anhydrous, oxygen-free conditions). | |
Key solvent (aromatic) | 108-88-3 | T399633 | Toluene (regulated) | Anhydrous, ≥99.8% | Often used for preparing/delivering organozinc reagents and for milder coupling systems; also commonly serves as the carrier solvent for solution reagents such as dimethylzinc. |
Polar aprotic solvent (backup system) | 68-12-2 | N,N-Dimethylformamide (DMF) | Anhydrous, ≥99.8% | Used for more polar organometallic/coupling systems and for poorly soluble substrates. Use with caution for organozinc reagents (ensure dryness; evaluate stability/side reactions). | |
Polar aprotic solvent (backup system) | 872-50-4 | N-Methyl-2-pyrrolidone (NMP) | Anhydrous, ≥99.5% | Suitable for high-polarity / low-solubility systems; used in some metal-catalyzed and solubilization strategies (organozinc stability should be verified at small scale). | |
Analytical / instrument solvent (nitrile) | 75-05-8 | Acetonitrile (ACN) | For DNA synthesis, H₂O ≤10 ppm | Commonly used for GC/LC sample preparation and analysis. Generally not the main solvent for organozinc reaction execution, but useful for workup, solvent controls, and quantitative analysis. | |
Workup / cleaning solvent (alcohol) | 67-56-1 | M116128 | Methanol | For protein sequencing, ≥99.9% | Commonly used for quenching, washing, recrystallization, or solvent exchange. Not typically used as the main solvent for organozinc reactions (it quenches organozinc species), but well-suited for workup stages. |
Workup / extraction solvent (ether, with stabilizer) | 60-29-7 | D1506342 | Diethyl ether (regulated) | For HPLC, ≥99%, stabilized with ethanol | A classic ether solvent; however, this grade contains ethanol stabilizer (a proton source). Not recommended as the primary solvent for organozinc generation/reaction. Better suited for extraction, workup, and solvent exchange. If used in organometallic reactions, treat “stabilizer/trace alcohol” as a key variable—evaluate via controls and ensure strict drying/deoxygenation. |
Table 3 | Cross-Coupling Catalysts & Ligands (Pd/Ni + Phosphine Ligands)
Category | CAS No. | Aladdin Cat. No. | Name | Grade / Purity | Uses & Selection Notes (Organozinc Reagents for Synthesis) |
Cross-coupling catalyst (Pd) | 3375-31-3 | Palladium(II) acetate (47% Pd) | For synthesis | A commonly used Pd(II) precatalyst/precursor to build various active Pd(0) species; compatible with Negishi and other cross-coupling systems (typically requires ligand and/or reduction to generate the active state). | |
Cross-coupling catalyst (Pd) | 13965-03-2 | Bis(triphenylphosphine)palladium(II) dichloride | Pd 15.2% | A widely used Pd catalyst containing PPh₃ ligands; suitable for Negishi and related couplings. Easy to start with and operationally mature—good for rapid validation and benchmarking. | |
Cross-coupling catalyst (Pd) | 72287-26-4 | [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) dichloride | Pd 14.5% | A typical Pd(dppf)Cl₂-type catalyst: often more robust for certain challenging substrates/heteroaryl substrates; commonly used in condition screening for Negishi/Suzuki and related couplings. | |
Cross-coupling catalyst (Pd) | 14221-01-3 | Tetrakis(triphenylphosphine)palladium(0) | Pd ≥8.9% | A pre-formed Pd(0) catalyst often used for rapid-start cross-couplings (including Negishi). Sensitive to air/oxygen—pay attention to storage and handling/charging methods. | |
Cross-coupling catalyst (Pd) | 51364-51-3 | Tris(dibenzylideneacetone)dipalladium(0) | ≥99.95% metals basis | Pd₂(dba)₃: commonly used as a Pd(0) source; generates active catalytic systems in situ with phosphine or carbene ligands. Suitable for ligand screening and for optimizing conditions for difficult substrates. | |
Cross-coupling catalyst (Ni) | 15629-92-2 | Nickel(II) chloride bis(diphenylphosphinopropane) complex | ≥98% | A NiCl₂(dppp)-type precatalyst used in developing and benchmarking Ni-catalyzed systems such as Negishi/Kumada; may be more economical and/or more efficient for certain substrates. | |
Cross-coupling catalyst (Ni, low-valent Ni source) | 1295-35-8 | Bis(1,5-cyclooctadiene)nickel(0) | ≥96% | Ni(cod)₂: a commonly used low-valent Ni(0) source for building active Ni catalytic systems (cross-coupling/reductive coupling, etc.). Air/moisture sensitive—use a glovebox or strictly inert techniques. | |
Cross-coupling catalyst (Ni, precatalyst) | 3264-82-2 | Nickel acetylacetonate | ≥95% | Ni(acac)₂: a widely used nickel precatalyst (requires reduction/ligand activation). Used for developing Ni-catalyzed couplings and for cost-friendly scale-up exploration. | |
Ligand (phosphine) | 603-35-0 | Triphenylphosphine (PPh₃) | ≥99% (GC) | A standard baseline phosphine ligand: forms active complexes with Pd/Ni; used to tune electronics/sterics and improve coupling selectivity and rate (a good “ligand baseline”). | |
Ligand (bisphosphine) | 12150-46-8 | 1,1′-Bis(diphenylphosphino)ferrocene (DPPF) | ≥99% | A commonly used bisphosphine; often more accommodating to certain heteroaryl/sterically hindered substrates; used to optimize activity and selectivity in Pd/Ni systems. | |
Ligand (bisphosphine) | 1663-45-2 | 1,2-Bis(diphenylphosphino)ethane (DPPE) | ≥98% | DPPE: a standard bisphosphine for tuning activity/selectivity in Pd/Ni systems; a foundational option for ligand screening. | |
Ligand (bisphosphine) | 6737-42-4 | 1,3-Bis(diphenylphosphino)propane (DPPP) | ≥97% | DPPP: a commonly used bisphosphine; used with Ni/Pd to tune coupling activity/selectivity (also the corresponding ligand for NiCl₂(dppp) complexes). |
Table 4 | Representative Electrophiles + Condition Control/Quench + Titration/Standardization Kit (Iodometric Titration Chain)
Category | CAS No. | Aladdin Cat. No. | Name | Grade / Purity | Uses & Selection Notes (Organozinc Reagents for Synthesis) |
Representative electrophile | benzyl halides | 100-44-7 | B431204 | Benzyl chloride | For synthesis | A common benchmark substrate/electrophile: can be used to prepare benzylzinc halides or as a performance control in Negishi coupling. High reactivity makes it convenient for condition screening. |
Representative electrophile | benzyl halides | 100-39-0 | Benzyl bromide | Moligand™, ≥98% (GC), stabilized with propylene oxide | A highly reactive benzylic electrophile widely used for condition screening/window exploration in Negishi and related couplings; also useful for constructing benzyl-related organozinc intermediates (requires inert, anhydrous handling). This product contains propylene oxide stabilizer, which may introduce side reactions or consume reactive species in organometallic/catalytic systems—recommend evaluating “stabilizer impact” as an explicit variable with control experiments. | |
Representative electrophile | aryl bromide (Negishi benchmark) | 108-86-1 | Bromobenzene | Standard for GC, ≥99.5% (GC) | A standard aryl-electrophile benchmark for Negishi coupling, suitable for rapid comparisons and method validation across catalyst/ligand/solvent systems. This GC-standard grade also supports quantitation and retention-time referencing. When aryl organozinc reagents are needed, they are more commonly prepared via transmetalation routes and then used in coupling. | |
Representative electrophile | aryl bromide (Negishi benchmark) | 106-38-7 | 4-Bromotoluene (p-bromotoluene) | ≥99% | A commonly used benchmark aryl bromide for Negishi coupling, enabling quick evaluation of catalyst/ligand/solvent/additive combinations; also useful as a “steric/electronic effect” comparison substrate. | |
Representative electrophile | aryl bromide (electron-rich control) | 104-92-7 | 4-Bromoanisole (p-bromoanisole) | ≥99% | An electron-rich aryl bromide electrophile, often used to test compatibility with electron-donating substituted substrates in Negishi coupling. A practical “electronic effect” control for comparing rate/selectivity differences among catalyst/ligand systems on electron-rich substrates. | |
Representative electrophile | aryl iodide | 591-50-4 | Iodobenzene | ≥99% | A more reactive aryl electrophile: useful for low-temperature/fast coupling benchmarks, or as an alternative when aryl bromides are difficult to couple. | |
Representative electrophile | allylic halide | 106-95-6 | Allyl bromide | ≥98%, contains ≤1000 ppm propylene oxide stabilizer | An allylic electrophile for building allyl-substituted products or as a reference for generating allylzinc intermediates. Note stabilizer effects and the risk of side reactions (polymerization/isomerization). | |
Representative electrophile | heteroaryl bromide (coordination-challenge control) | 109-04-6 | 2-Bromopyridine | ≥98% | A representative heteroaryl electrophile for assessing compatibility with N-heterocycles in Negishi coupling (prone to coordination, may inhibit catalysis or trigger side pathways—i.e., a typical “difficult substrate”). Well-suited for ligand/catalyst screening and additive-strategy benchmarking. | |
Representative electrophile | heteroaryl bromide (sulfur-heterocycle control) | 1003-09-4 | 2-Bromothiophene | ≥98% | A sulfur-containing heteroaryl electrophile for evaluating sulfur-heterocycle compatibility and catalyst-system tolerance in Negishi coupling. Commonly used as a condition-screening benchmark to identify more robust ligand/catalyst combinations for sulfur-containing substrates. | |
Representative electrophile | α-bromo ester | 535-11-5 | Ethyl 2-bromopropionate | ≥99% | One of the common substrates for Reformatsky/organozinc insertion; used to generate α-carbonyl-substituted organozinc intermediates or as a coupling benchmark, facilitating evaluation of functional-group tolerance under different conditions. | |
Representative electrophile | α-bromo ester | 600-00-0 | Ethyl 2-bromoisobutyrate | ≥98% | A typical α-bromo ester used to generate the corresponding organozinc intermediate or as a coupling benchmark. Useful for mapping the reaction window for more sterically demanding α-substituted substrates. | |
Representative electrophile | α-bromo ester | 105-36-2 | E106090 | Ethyl bromoacetate | ≥98% | A classic substrate for Reformatsky/organozinc insertion; often used to generate ester-stabilized organozinc species or as a benchmark addition/coupling reaction. |
Representative electrophile | α-bromo ester (more sterically demanding) | 5292-43-3 | tert-Butyl bromoacetate | ≥98% | The tert-butyl ester can be advantageous for downstream deprotection/selective handling. Used to evaluate how a bulkier ester affects insertion/coupling behavior and functional-group tolerance. | |
Representative electrophile | α-bromo ester | 96-32-2 | Methyl bromoacetate | ≥97% | The methyl-ester version of an α-bromo ester: used for Reformatsky/organozinc insertion and benchmarking; convenient for comparing how ester identity influences rate/selectivity. | |
Representative electrophile | α-bromo nitrile | 22115-41-9 | α-Bromo-o-methyl benzonitrile | ≥98% | A functionalized electrophile benchmark for evaluating tolerance/selectivity toward nitriles and sterically hindered aromatic systems; also useful for constructing benzylic/α-functionalized products. | |
Representative electrophile | acyl chloride | 3282-30-2 | T109597 | Pivaloyl chloride | ≥98% | A representative acyl chloride electrophile. Can be used for acylation with organozinc/metal intermediates to build ketones; also frequently used in protection/activation strategies and condition screening. |
Quench / salt-effect additive (ammonium salt) | 12125-02-9 | Ammonium chloride | For cell culture | A commonly used mild quench/workup salt: terminates reactions, breaks complexes, and promotes phase separation. Also useful for preparing/comparing organozinc reactivity under different halide/salt environments. | |
Additive / acid (condition control; PivOH) | 75-98-9 | Trimethylacetic acid (PA) | ≥99% | Pivalic acid (PivOH): can serve as an acidic additive/control to modulate catalytic cycles, salt forms, or intermediate equilibria; also useful for comparing how different carboxylic-acid environments influence rate/selectivity. Whether it provides a clear “gain” is highly system-dependent—recommend validating via small-scale controls. | |
Analytical / titration auxiliary (iodometry) | 7681-11-0 | Potassium iodide | Anhydrous, high purity, reagent grade, ≥99% | In iodometry, commonly used to generate I₃⁻ (improves iodine solubility in the aqueous phase and stabilizes the titration). Used together with iodine solution/starch/sodium thiosulfate for organozinc standardization and activity assessment; can also serve as a halide-salt additive for “salt effect” controls. | |
Analytical indicator (iodometric endpoint) | 9005-84-9 | Soluble starch | Pharmaceutical grade, PharmPure™ | A standard starch indicator for iodometric titration (forms a colored complex with I₂/I₃⁻) to determine the endpoint; suitable as a supporting consumable for organozinc titration/standardization and activity assessment. | |
Analytical reagent (standard iodine solution) | 7553-56-2 | I197264 | Iodine concentrate | Dilute to 1 L; concentration after dilution: 0.05 M | A typical quantified iodine source for determining organozinc concentration/activity (iodometry). Together with KI/starch/sodium thiosulfate, it forms a complete titration chain. |
Analytical / titration reagent (reducing titrant) | 10102-17-7 | Sodium thiosulfate pentahydrate | Ph. Eur., suitable for analysis, ACS, reagent grade | A standard reducing titrant for back-titrating/titrating I₂ in iodometry. Used with iodine solution and starch indicator to complete quantitative determination of organozinc reagents. |
Note: The above are representative Aladdin products. For additional specifications, please refer to the product list at the end of the article or search by product name/CAS on the Aladdin website.