Organozinc compounds in organic chemistry contain carbon to zinc chemical bonds. Organozinc chemistry is the science of organozinc compounds describing their physical properties, synthesis and reactions.
Organozinc compounds were among the first organometallic compounds made. These organozinc compounds are less reactive and thus more selective than other analogous organometallic reagents, such as Grignard reagents. In 1848 Edward Frankland prepared the first organozinc compound, diethylzinc, by heating ethyl iodide in the presence of zinc metal. This reaction produced a volatile colorless liquid that was pyrophoric, spontaneous combusting in the presence of air. Due to this pyrophoric nature an inert gas blank (nitrogen or argon) is always used when preparing these compounds. Organozinc compounds in general are sensitive to oxidation, dissolve in a wide variety of solvents where protic solvents cause decomposition. In many reactions they are prepared in situ, not isolated, but in some cases may be isolated in the vapor phase. 
- Diorganozinc (R2Zn): A class of organozinc compounds in which two alkyl substituents are coordinated directly to the metal but may be further divided into subclasses depending on the other ligands attached
- Heteroleptic (RZnX): Compounds which an electronegative or monoanionic ligand (X), such as a halogen, is attached to the central zinc atom with another alkyl or aryl substituent (R).
- Ionic organozinc compounds: This class is divided in to organozincates (RnZn-) and organozinc cations (RnZn+).
- 1 Background
- 2 Synthesis
- 3 Reactions
- 4 Organozincates
- 5 Organozinc(I) compounds
- 6 See also
- 7 References
- 8 External links
Zinc coordination complexes most commonly exist as four-coordinate (transition word) tetrahedral or trigonal pyramidal molecular geometries. These structural characteristics can be attributed to zinc’s electronic configuration [Ar]3d104s2 when zinc is in the +2 oxidation state. The low lying 3d orbital is full and symmetrical. Coordination behavior around the central zinc atom is thus determined largely by electrostatic interactions. Therefore, these orbitals do not cause any ligand field effects. Electron-donating group, such as chlorine, aid in the stabilization of these unsaturated organometallic structures. 
In typical diorganozinc comples, R2Zn, the central zinc atom forms a polar covalent bond, in which the carbon-zinc bond is polarized toward carbon due to the differences in Pauling electronegativity values (carbon: 2.5 & zinc: 1.65).Even though zinc is significantly more electropositive, the dipole moment of symmetric diorganozinc reagents can be seen as zero in non-polar solvents like cyclohexane. Unlike other similar organometallic reagents, the symmetric diorganozinc species shows a low tendency for complexation with ethereal solvent. In this case, two equivalent sp-hybridized zinc orbitals will form. 
These structures cause zinc to have two bonding d-orbitals and four low-lying non-bonding d-orbitals (see non-bonding orbital), which are available for binding. When zinc lacks electron donating ligands it is unable to obtain coordination saturation, which is a consequence of the large atomic radius and low electron deficiency of zinc. Therefore it is rare for bridging alkyl or aryl groups to occur due to the weak electron deficiency of the zinc atom. Although, it does occur in some cases such as Ph2Zn (Shown below) and which halogens are the organozinc can form metal clusters (see cluster chemistry). When a halogen ligand is added to the zinc atom both the acceptor and donor character of zinc is enhanced allowing for aggregation. 
Several general methods exist for the generation of organozinc compounds.
Frankland’s original synthesis of diethylzinc was an oxidative process of ethyl iodide to zinc metal. This reaction required a source of activated zinc, due to the redox inactive nature of Zn2+. One of these sources that Frankland used was Zinc-copper couple.
- Riecke Zinc: (see Rieke metals) This is a useful way of reducing Zn2+ to a reactive source of zinc using potassium. The oxidative addition product generates useful precursors for reactions such as Negishi coupling and Fukuyama coupling. The R group participating in the oxidative addition typically has another functional group handle that withdraws electron density, making the oxidative addition more facile. Examples of these groups are esters, halides, enolates, cyano-, ect.  
Functional group exchange
The two most common zinc functional group interconversion reactions are with halides and boron, which is catalyzed by copper iodide (CuI) or base. The boron intermediate is synthesized by an initial hydroboration reaction followed by treatment with diethyl zinc. This synthesis shows the utility of organozinc reagents by displaying high selectivity for the most reactive site in the molecule, as well as creating useful coupling partners.
β-Silyl Diorganozinc compounds
One of the major drawbacks of diorganozinc alkylations is that only one of the alkyl substituents is transferred. This is a huge disadvantage if the transferring substituent is highly functionalized. Knochel has developed a method of getting around this by using Me2SiCH2 (TMSM), which is a non-transferable group. 
Transmetallation is similar to the interconversions displayed above zinc can exchange with other metals such as mercury, lithium, copper, ect. One example of this is diphenylmercury reacting with zinc metal to form diphenylzinc and metallic mercury in diethyl ether. The benefit of transmetalling to zinc it is often more tolerant of other functional groups in the molecule due to the low reactivity which increases selectivty. 
- In Armen Zakarian’s synthesis of Maoecrystal V, an directed ortho metalation gives the initial aryl-lithium species, which is transmetallated to the desired arylzinc compound. The arylzinc compound is significantly less reactive than the aryl-lithium species and thus better tolerates the functionality in the subsequent coupling with methyl chlorooxaloacetate. Esters are significantly stable against organozinc reagents.
- In this method zinc is activated by 1,2-dibromoethane and trimethylsilyl chloride. A key ingredient is lithium chloride which quickly forms a soluble adduct with the organozinc compound thus removing it from the metal surface.
In many of their reactions organozincs appear as intermediates.
- In the Frankland–Duppa reaction (1863) an oxalate ester (ROCOCOOR) reacts with an alkyl halide R'X, zinc and hydrochloric acid to the α-hydroxycarboxylic esters RR'COHCOOR
This organic reaction can be employed to convert α-haloester and ketone or aldehyde to a β-hydroxyester. Acid is needed to protonate the resulting alkoxide during work up. The initial step is an oxidative addition of zinc metal into the carbon-halogen bond, thus forming a carbon-zinc enolate. This C-Zn enolate can then rearrange to the Oxygen-Zinc enolate via coordination. Once this is formed the other carbonyl containing starting material will coordinate in the manner shown below and give the product after protonation. The benefits of the Reformatsky reaction over the convential aldol reaction protocols is the following:
- Allows for exceedingly derivatized ketone substrates
- The ester enolate intermediate can be formed in the presence of enolizable moieties
- Well suited for intramolecular reactions
The Reformatsky reaction has been employed in numerous total syntheses such as E. Vedejs’ synthesis of C(16),C(18)-bis-epi-cytochalasin D:
The Reformatsky reaction even allows for with zinc homo-enolates. 
The Simmons-Smith can cylcloproponate an olefin using methylene iodide and zinc metal. The key zinc-intermediate formed is a carbcarbenoid (iodomethyl)zinc iodide which reacts with alkenes to afford the cyclopropanated product. The rate of forming the active zinc species is increased via ultrasonication since the initial reaction occurs at the surface of the metal.
Allow the mechanism has not been fully elaborated it is hypothesized that the organozinc intermediate is a metal-carbenoid. The intermediate is believed to be a three-centered "butterfly-type" intermediate This intermediate can be directed by substituents, such as alcohols, to deliver the cyclopropane on the same side of the molecule. Zinc-Copper Couple is commonly used to activate zinc. 
This is a powerful carbon-carbon bond forming cross-coupling reaction using an organic halide ,an organozinc halide reagent, and a nickel or palladium catalyst. The organic halide reactant must either be alkenyl, aryl, allyl, or propargyl. A key step in the catalytic cycle is a transmetalation in which a zinc halide exchanges its organic substituent for another halogen with the metal center. Although in comparison to other cross-coupling reactions such as Suzuki, Heck or Stille coupling, the Negishi reaction has been underdeveloped. Either diorganic species or organozinc halides can be used as coupling partners during the transmetallation step in this reaction. Despite the low reactivity of organozinc reagents on organic electrophiles, these reagents are among the most powerful metal nucleophiles toward palladium. 
An elegant example of Negishi coupling is shown below with Furstner and co-workers’ synthesis of amphidinolide T1.
Fukuyama coupling is a palladium involving the coupling of an aryl, alkyl, allyl, or α,β- unsaturated thioester compound. This thioester compound can be coupled to a wide range of organozinc reagents in order to reveal the corresponding ketone product. This protocol is useful due to its sensitivity to functional groups such as ketone, acetate, aromatic halides, and even aldehydes. The chemoselectivity observed indicates ketone formation is more facile than oxidative addition of palladium into these other moieties.
The Barbier reaction is a nucleophilic addition reaction into a carbonyl, similar to the Grignard reaction. The organozinc reagent is made via an oxidative addition into the alkyl halide. The reaction produces a primary, secondary, or tertiary alcohol via a 1,2-addition. The benefit of using the Barbier reaction is that it allows convenient one-pot synthesis of the organozinc reagent in the presence of the carbonyl compound. Organozinc reagents are also less water sensative and thus running the reactions in water are permitted. Similar to the Grignard reaction, a schlenk equilibrium is displayed, in which the more reactive dialkylzinc can be formed. 
The mechanism resembles the Grignard reaction, in which the metal alkoxide can be generated by a radical stepwise pathway, through single electron transfer, or concerted reaction pathway via a cyclic transition state. An example of this reaction is in Samuel Danishefsky’s total synthesis of Cycloproparadicicol. By using the organozinc addition reaction conditions the other functionality of the dienone and the alkyne are tolerated. 
Among the Group 12 elements zinc is the most reactive. Commercially available diorganozinc compounds are dimethylzinc, diethylzinc and diphenylzinc. These reagents are expensive and difficult to handle. In one study the active organozinc compound is obtained from much cheaper organobromine precursors:
The synthesis of of (+)-aspicillin, starts first with a hydroboration, then transmetallation to zinc which can then do an addition into the aldehyde substituent.
Zinc Metal Acetylides
The formation of the zinc acetylide goes via the intermediacy of a dialknyl zinc (functional group exchange). Catalytic processes have been developed such as Merck’s ephedrinee process. Propargylic alcohols can be synthesized via this zinc acetylide route. These versatile intermediates can then be used for a wide range of chemical transformations such as cross-coupling reactions, hydrogenation, and pericyclic reactions. 
When no ligand is present the reaction goes extremely slow with low yields (30%). Addition of a chiral ligand gives high conversion with low reaction times (ligand acceleration). Ryoji Noyori determined the zinc-ligand monomer is the active species in the reaction. 
- The α-stereocenter of the ligand dictates observed stereochemistry of the propargylic alcohols
- The steric effects between the aldehyde substituent and the ligand are less important but still dictate the favored conformation
Organozinc compounds that are strong Lewis acids at the zinc metal center are vulnerable to nucleophilic attack by alkali metals, such as sodium, and thus form these ‘ate compounds’. There are two types of organozincates: tetraorganozincates ([R4Zn]M2), dianionic and triorganozincates ([R3Zn]M), monoanionic. The structure of the zincate depends the donor ligands as well addition solvent donor molecules. Zincate structures have been determined by NMR, Ultraviolet-Visible Spectroscopy, Raman Spectroscopy, EXAFS, and X-Ray Crystallography. 
Tetraorganozincates such as [Me4Zn]Li2 can be formed by mixing Me2Zn and MeLi in a 1:2 molar ratio of the rectants. Another example synthetic route to forming spriocyclic organozincates is shown below: 
Triorganozincates compounds are formed by reacting a diorganozinc such as (Me3SiCH2)2Zn with an alkali metal (K), or an alkali earth metal (Ba, Sr, or Ca) to afford the triorganozincate, [(Me3SiCH2)3Zn]K. In 2007 it was reported that by tweaking the reaction conditions the zincate proceeds to react to sodium hydridoethylzincate(II) (with hydrogen atoms as bridging ligands) as a result of beta-hydride elimination of one of the ethyl groups:
Organozincates often have increased reactivity and selectivity compared to the diorganozinc compounds. Although often underutilized organozincates reagents are useful in stereoselective alkylations of ketones, nucleophillic addition to carbonyls, ring opening reactions, and oxovandium ligand coupling of aryltrimethylzincates (shown below). 
- Compounds of zinc
- Compounds of carbon with other elements in the periodic table:
|Core organic chemistry||Many uses in chemistry|
|Academic research, but no widespread use||Bond unknown|
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