Gilman reagent

File:Cuprate_conjugate_addition_with_lewis_acid.png

These reagents are useful because, unlike related Grignard reagents and organolithium reagents, they react with organic halides to replace the halide group with an R group (the Corey–House reaction). Such displacement reactions allow for the synthesis of complex products from simple building blocks.{{cite journal | title = Organocopper(I) Compounds and Organocuprates in Synthesis| journal = Synthesis | author = J. F. Normant| pages = 63–80| doi = 10.1055/s-1972-21833| volume = 1972 | issue = 2| year = 1972}}{{Cite journal |last=Woodward |first=Simon |date=2000-01-01 |title=Decoding the 'black box' reactivity that is organocuprate conjugate addition chemistry |url=https://pubs.rsc.org/en/content/articlelanding/2000/cs/b002690p |journal=Chemical Society Reviews |language=en |volume=29 |issue=6 |pages=393–401 |doi=10.1039/B002690P |issn=1460-4744|url-access=subscription }} Lewis acids can be used to modify the reagent.

{{Image frame|content=$$

[\ce{R}{-}{\color{Blue}\ce{Cu}}\ce{-R}]^-\ce{Li+}\

\xrightarrow{\color{Red}\ce{R'-X}}\

\overbrace{\left[\ce R{-}\overset{{\displaystyle \color{Red} \ce R'} \atop |}\underset{| \atop {\displaystyle \color{Red} \ce X}}{\color{Blue}\ce{Cu}}\ce{-R} \right]^-\ce{Li+}}^\text{planar intermediate}

\ce{-> R}{-}{\color{Blue}\ce{Cu}} + \ce{R}{-}{\color{Red}\ce{R'}} + \ce{Li}{-}{\color{Red}\ce{X}}

|align=center|width=540|caption=Generalized chemical reaction showing Gilman’s reagent reacting with organic halide to form products and showing Cu(III) reaction intermediate}}

These reagents were discovered by Henry Gilman and coworkers.{{cite journal | title = The Preparation of Methylcopper and some Observations on the Decomposition of Organocopper Compounds| author = Henry Gilman, Reuben G. Jones, and L. A. Woods| pages = 1630–1634| journal = Journal of Organic Chemistry| doi = 10.1021/jo50012a009| volume = 17| issue = 12| year = 1952}} Lithium dimethylcopper (CH₃)₂CuLi can be prepared by adding copper(I) iodide to methyllithium in tetrahydrofuran at −78 °C. In the reaction depicted below,Modern Organocopper Chemistry, N. Krause Ed. Wiley-VCH, 2002. the Gilman reagent is a methylating reagent reacting with an alkyne in a conjugate addition, and the ester group forms a cyclic enone.

Image:Gilman reaction example.png

:File:Gilman vs Grignard.jpg

Lithium dimethylcuprate exists as a dimer in diethyl ether forming an 8-membered ring. Similarly, lithium diphenylcuprate crystallizes as a dimeric etherate, {{chem2|[{Li(OEt2)}(CuPh2)]2}}.{{cite journal | journal = Angew. Chem. Int. Ed. | volume = 29 | issue = 3 | pages = 300–302 | year = 1990 |author1=N. P. Lorenzen |author2=E. Weiss | doi = 10.1002/anie.199003001 | title = Synthesis and Structure of a Dimeric Lithium Diphenylcuprate:[{Li(OEt)₂}(CuPh₂)]₂}}

If the Li⁺ ions is complexed with the crown ether 12-crown-4, the resulting diorganylcuprate anions adopt a linear coordination geometry at copper.{{ cite journal | journal = Journal of the American Chemical Society | title = Isolation and x-ray crystal structures of the mononuclear cuprates [CuMe₂]⁻, [CuPh₂]⁻, and [Cu(Br)CH(SiMe₃)₂]⁻ |author1=H. Hope |author2=M. M. Olmstead |author3=P. P. Power |author4=J. Sandell |author5=X. Xu | year = 1985 | volume = 107 | issue = 14 | pages = 4337–4338 | doi = 10.1021/ja00300a047| bibcode = 1985JAChS.107.4337H }}

For the 'higher order cyanocuprate' Li₂CuCN(CH₃)₂, Lipshutz and coworkers have claimed that the cyanide ligand is coordinated to Li and π-bound to Cu.{{cite journal|author=Bruce H. Lipshutz; Brian James|title=New 1H and 13C NMR Spectral Data on "Higher Order" Cyanocuprates. If the Cyano Ligand Is Not On Copper, Then Where Is It?|journal=J. Org. Chem.|year=1994|volume=59 |issue=25 |pages=7585–7587|doi=10.1021/jo00104a009}} However, the existence of 'mixed higher order organocuprates' has been disputed by Bertz and coworkers, who rejoined that the cyano ligand is actually bound solely to the lithium atom, and that such a structure could still explain the enhanced reactivity of cuprate prepared from CuCN.{{Cite journal |last=Bertz |first=Steven H. |last2=Miao |first2=Guobin |last3=Eriksson |first3=Magnus |date=1996-01-01 |title=It's on lithium! an answer to the recent communication which asked the question: ‘if the cyano ligand is not on copper, then where is it?’ |url=https://pubs.rsc.org/en/content/articlelanding/1996/cc/cc9960000815 |journal=Chemical Communications |language=en |issue=7 |pages=815–816 |doi=10.1039/CC9960000815 |issn=1364-548X|url-access=subscription }}{{Cite web |last=Bertz |first=Steven H. |date=2002-05-01 |title=New copper chemistry. 17. Higher-order cyanocuprates: are they real? |url=https://pubs.acs.org/doi/pdf/10.1021/ja00166a046 |access-date=2025-04-18 |website=ACS Publications |language=EN |doi=10.1021/ja00166a046}} To date, no crystallographic evidence for the existence of 'mixed higher order cuprates' ([R₂CuX]^2–, X ≠ R) has been obtained. On the other hand, a homoleptic higher order cuprate in the form of a [Ph₃Cu]^2– moiety has been observed in Li₃Cu₂Ph₅(SMe₂)₄, prepared by Olmstead and Power.{{Cite journal |last=Olmstead |first=Marilyn M. |last2=Power |first2=Philip P. |date=1989-05-01 |title=Structural characterization of a higher order cuprate: x-ray crystal structure of [Li3Cu2Ph5(SMe2)4] |url=https://pubs.acs.org/doi/10.1021/ja00193a075 |journal=Journal of the American Chemical Society |volume=111 |issue=11 |pages=4135–4136 |doi=10.1021/ja00193a075 |issn=0002-7863|url-access=subscription }}

More useful generally than the Gilman reagents are the so-called mixed cuprates with the formula [RCuX]⁻ and [R₂CuX]²⁻ (see above for the controversy over existence of the latter). Such compounds are often prepared by the addition of the organolithium reagent to copper(I) halides and cyanide. These mixed cuprates are more stable and more readily purified.Steven H. Bertz, Edward H. Fairchild, Karl Dieter, "Copper(I) Cyanide" in Encyclopedia of Reagents for Organic Synthesis 2005, John Wiley & Sons. {{doi|10.1002/047084289X.rc224.pub2}} One problem addressed by mixed cuprates is the economical use of the alkyl group. Thus, in some applications, the mixed cuprate with the formula {{chem|Li|2|[Cu(2-thienyl)(CN)R]}} is prepared by combining thienyllithium and cuprous cyanide followed by the organic group to be transferred. In this higher order mixed cuprate, both the cyanide and thienyl groups do not transfer, only the R group does.Bruce H. Lipshutz, Robert Moretti, Robert Crow "Mixed Higher-order Cyanocuprate-induced Epoxide Openings: 1-Benzyloxy-4-penten-2-ol" Org. Synth. 1990, volume 69, pp. 80. {{doi|10.15227/orgsyn.069.0080}}

• Cuprate (chemistry)

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