Organocopper

compound

Organocopper compounds in organomet allic chemist ry cont ain carbon t o copper chemical
bonds. Organocopper chemistry is t he science of organocopper compounds describing t heir
physical propert ies, synt hesis and react ions.[1][2][3] They are reagent s in organic chemist ry.

Lithium diphenylcuprate etherate dimer from crystal structure

Skeletal formula of lithium diphenylcuprate etherate dimer

The first organocopper compound, t he explosive copper(I) acet ylide Cu2C2 (Cu-C≡C-Cu), was
synt hesized by Rudolf Christ ian Böt t ger in 1859 by passing acet ylene gas t hrough copper(I)
chloride solut ion:[4]

C2H2 + 2 CuCl → Cu2C2 + 2 HCl

Structure and bonding

Organocopper compounds are diverse in st ruct ure and react ivit y, but organocopper compounds
are largely limit ed in oxidat ion st at es t o copper(I), somet imes denot ed Cu+ . As a d10 met al
cent er, it is relat ed t o Ni(0), but owing t o it s higher oxidat ion st at e, it engages in less pi-
backbonding. Organic derivat ives of Cu(II) and Cu(III) are invoked as int ermediat es but rarely
isolat ed or even observed. In t erms of geomet ry, copper(I) adopt s symmet rical st ruct ures, in
keeping wit h it s spherical elect ronic shell. Typically one of t hree coordinat ion geomet ries is
adopt ed: linear 2-coordinat e, t rigonal 3-coordinat e, and t et rahedral 4-coordinat e. Organocopper
compounds form complexes wit h a variet y of soft ligands such as alkylphosphines (R3P),
t hioet hers (R2S), and cyanide (CN−).

Simple complexes with CO, alkene, and Cp ligands

Copper(I) salt s have long been known t o bind CO, albeit weakly. A represent at ive complex is
CuCl(CO), which is polymeric. In cont rast t o classical met al carbonyls, pi-backbonding is not
st rong in t hese compounds.[5]
Part of the framework of CuCl(CO). In this coordination polymer, the Cu centers are tetrahedral linked by triply bridging
chloride ligands.

Alkenes bind t o copper(I), alt hough again generally weakly. The binding of et hylene t o Cu in
prot eins is of broad significance in plant biology so much so t hat et hylene is classified as a plant
hormone. It s presence, det ect ed by t he Cu-prot ein, affect s ripening and many ot her
development s.[6]

Alt hough copper does not form a met allocene, half-sandwich complexes can be produced. One
such derivat ive is (η-cyclopent adienyl t riet hylphosphine) copper.[7]

Alkyl and aryl copper compounds

Alkyl and aryl copper(I) compounds

Copper halides react wit h organolit hium reagent s t o give organocopper compounds. The area
was pioneered by Henry Gilman, who report ed met hylcopper in 1936. Thus, phenylcopper is
prepared by react ion of phenyllit hium wit h copper(I) bromide in diet hyl et her. Grignard reagent s
can be used in place of organolit hium compounds. Gilman also invest igat ed t he dialkylcuprat es.
These are obt ained by combining t wo equivalent of RLi wit h Cu(I) salt s. Alt ernat ively, t hese
cuprat es are prepared from oligomeric neut ral organocopper compounds by t reat ment wit h one
equivalent of organolit hium reagent .

Compounds of t he t ype [CuRn](n-1)- are react ive t owards oxygen and wat er, forming copper(I)
oxide. They also t end t o be t hermally unst able, which can be useful in cert ain coupling react ions.
Despit e or because of t hese difficult ies, organocopper reagent s are frequent ly generat ed and
consumed in sit u wit h no at t empt t o isolat e t hem. They are used in organic synt hesis as
alkylat ing reagent s because t hey exhibit great er funct ional group t olerance t han corresponding
Grignard and organolit hium reagent s. The elect ronegat ivit y of copper is much higher t han it s
next -door neighbor in t he group 12 element s, zinc, suggest ing diminished nucleophilicit y for it s
carbon ligands.

Copper salt s react wit h t erminal alkynes t o form t he acet ylides.

Alkyl halides react wit h organocopper compounds wit h inversion of configurat ion. On t he ot her
hand, react ions of organocopper compound wit h alkenyl halides proceed wit h ret ent ion of
subt rat e’s configurat ion.[8]

Organocopper compounds couple wit h aryl halides:

Structures

Alkyl and aryl copper complexes aggregat e bot h in cryst alline form and in solut ion. Aggregat ion is
especially evident for charge-neut ral organocopper compounds, i.e. species wit h t he empirical
formula (RCu), which adopt cyclic st ruct ures. Since each copper cent er requires at least t wo
ligands, t he organic group is a bridging ligand. This effect is illust rat ed by t he st ruct ure of
mesit ylcopper, which is a pent amer. A cyclic st ruct ure is also seen for CuCH2SiMe 3, first 1:1
organocopper compound t o be analyzed by X-ray cryst allography (1972 by Lappert ). This
compound is relat ively st able because t he bulky t rimet hylsilyl groups provide st eric prot ect ion.
It is a t et ramer, forming an 8-membered ring wit h alt ernat ing Cu-C bonds. In addit ion t he four
copper at oms form a planar Cu4 ring based on t hree-cent er t wo-elect ron bonds. The copper t o
copper bond lengt h is 242 pm compared t o 256 pm in bulk copper. In pentamesitylpentacopper a
5-membered copper ring is formed, similar t o (2,4,6-t rimet hylphenyl)gold, and
pentafluorophenylcopper is a t et ramer.[9]
Lit hium dimet hylcuprat e is a dimer in diet hyl et her, forming an 8-membered ring wit h t wo lit hium
at oms linking t wo met hyl groups. Similarly, lit hium diphenylcuprat e forms a dimeric et herat e,
[{Li(OEt 2)}(CuPh2)]2, in t he solid st at e.[10]

Alkyl and aryl copper(III) compounds

The involvement of t he ot herwise rare Cu(III) oxidat ion st at e has been demonst rat ed in t he
conjugat e addit ion of t he Gilman reagent t o an enone:[11] In a so-called rapid-inject ion NMR
experiment at -100 °C, t he Gilman reagent Me 2CuLi (st abilized by lit hium iodide) was int roduced
t o cyclohexenone (1) enabling t he det ect ion of t he copper — alkene pi complex 2. On
subsequent addit ion of t rimet hylsilyl cyanide t he Cu(III) species 3 is formed (indefinit ely st able
at t hat t emperat ure) and on increasing t he t emperat ure t o -80 °C t he conjugat e addit ion product
4. According t o an accompanying in silico experiment s [12] t he Cu(III) int ermediat e has a square
planar molecular geomet ry wit h t he cyano group in cis orient at ion wit h respect t o t he
cyclohexenyl met hine group and ant i-parallel t o t he met hine prot on. Wit h ot her ligands t han t he
cyano group t his st udy predict s room t emperat ure st able Cu(III) compounds.

Reactions of organocuprates

Cross-coupling reactions

Prior t o t he development of palladium-cat alyzed cross coupling react ions, copper was t he
preferred cat alyst for almost a cent ury. Palladium offers a fast er, more select ive react ion.
However, in recent years copper has reemerged as a synt het ically useful met al, because of it s
lower cost and because it is an eco-friendly met al.[13]

React ions of R2CuLi wit h alkyl halides R'-X give t he coupling product :
 R2CuLi + R'X → R-R' + CuR + LiX

The react ion mechanism involves oxidat ive addit ion (OA) of t he alkyl halide t o Cu(I), forming a
planar Cu(III) int ermediat e, followed by reduct ive eliminat ion (RE). The nucleophilic at t ack is t he
rat e-det ermining st ep. In t he subst it ut ion of iodide, a single-elect ron t ransfer mechanism is
proposed (see figure).

Many elect rophiles part icipat e in t his react ion. The approximat e order of react ivit y, beginning
wit h t he most react ive, is as follows: acid chlorides[14] > aldehydes > t osylat es ~ epoxides >
iodides > bromides > chlorides > ket ones > est ers > nit riles >> alkenes

Generally t he OA-RE mechanism is analogous t o t hat of palladium-cat alyzed cross coupling

react ions. One difference bet ween copper and palladium is t hat copper can undergo single-
elect ron t ransfer processes.[8]

Coupling reactions

Oxidat ive coupling is t he coupling of copper acet ylides t o conjugat ed alkynes in t he Glaser
coupling (for example in t he synt hesis of cyclooct adecanonaene) or t o aryl halides in t he Cast ro-
St ephens Coupling.

Reduct ive coupling is a coupling react ion of aryl halides wit h a st oichiomet ric equivalent of
copper met al t hat occurs in t he Ullmann react ion. In an example of a present -day cross coupling
react ion called decarboxylative coupling, a cat alyt ic amount of Cu(I) displaces a carboxyl group
forming t he arylcopper (ArCu) int ermediat e. Simult aneously, a palladium cat alyst convert s an aryl
bromide t o t he organopalladium int ermediat e (Ar'PdBr), and on t ransmet allat ion t he biaryl is
formed from ArPdAr'.[15][16]

Redox neut ral coupling is t he coupling of t erminal alkynes wit h halo-alkynes wit h a copper(I) salt
in t he Cadiot -Chodkiewicz coupling. Thermal coupling of t wo organocopper compounds is also
possible.

Carbocupration

Carbocupration is a nucleophilic addit ion of organocopper reagent s (R-Cu) t o acet ylene or

t erminal alkynes result ing in an alkenylcopper compound (RC=C-Cu).[17] It is a special case of
carbomet alat ion and also called t he Normant reaction.[18]

Figure: Cat alyt ic cycle for carbocuprat ion for t he Synt hesis of Aldol, Baylis-Hillman Type
Product s[19]
 Synthetic applications

The Chan-Lam coupling enables t he format ion of aryl carbon-het oroat om bonds. It involves
coupling of boronic acids, st annanes, or siloxanes wit h NH- or OH-cont aining subst rat es.

Ullmann react ion involves copper-mediat ed react ions of aryl halides. Two t ypes of Ullmann
react ion are recognized:

Classic copper-promot ed synt hesis of symmet ric biaryl compounds)

Copper-promot ed nucleophilic aromat ic subst it ut ion.

Sonogashira coupling react ion, which ut ilizes bot h copper and palladium, ent ails t he coupling of
aryl and/or vinyl halides wit h t erminal alkynes.

Reducing agents

Copper hydrides are specialized reagent s used occasionally as reducing agent . The best known
copper hydride is called St ryker's reagent , a clust er compound wit h t he formula [(PPh3)CuH]6. It
reduces t he alkene α,β-unsat urat ed carbonyl compounds.[20]

The Buchwald react ion is a copper-cat alyzed asymmet ric reduct ion of act ivat ed alkenes. The
reagent is generat ed in sit u from copper(I) NHC complex. The hydride equivalent s are provided
by a silane.[21][22]

Synt hesis of Z-Fluoro alkene dipept ide isost eres,.[23][24] Ot her effort t o make t his a more
select ive react ions includes t he use of oxidat ion reduct ion condit ion for t he react ion.[25] Fluoride
act s as a leaving group and it enhances regioselect ivit y in t he t ransformat ion t he Z- fluoroalkene.

Cu alkylation reaction

Generally, t he alkylat ion react ion of organocopper reagent s proceed via gamma- alkylat ion. Cis-
gamma at t ack occurs bet t er in cyclohexyl carbamat e due t o st erics. The react ion is report ed t o
be favorable in et hereal solvent s. This met hod was proved t o be very effect ive for t he oxidat ive
coupling of amines and alkyl, including t ert but yl, and aryl halides.[26]

Vicinal functionalization reactions

Vicinal funct ionalizat ion using a Carbocuprat ion- Mukaiyama aldol react ion sequence [27]
Muller and collaborat ors report ed a vicinal funct ionalizat ion of α,β- acet ylenic est ers using a
Carbocuprat ion/ Mukaiyama aldol react ion sequence (as shown in fig above) carbocuprat ion
favors t he format ion of t he Z- aldol.

Further reading

Yao, B.; Liu, Y.; Zhao, L.; Wang, D.; Wang, M. (2014). "Designing a Cu(II)−ArCu(II)−ArCu(III)−Cu(I)
Cat alyt ic Cycle: Cu(II)-Cat alyzed Oxidat ive Arene C−H Bond Azidat ion wit h Air as an Oxidant
under Ambient Condit ions". J. Org. Chem. 79 (22): 11139–11145. doi:10.1021/jo502115a (ht t p
s://doi.org/10.1021%2Fjo502115a) . PMID 25350606 (ht t ps://pubmed.ncbi.nlm.nih.gov/2535
0606) .

Yamamot o, Y.; Yamammot o, S.; Yat agai, H.; Maruyama, K (1980). "Lewis acid mediat ed react ions
of organocopper reagent . A remarkably enhanced regioselect ive gamma- at t ack of allylic
halides and direct alkylat ion of allylic alcohols via RCu.BF3". JACS. 102 (7): 2318–2325.
doi:10.1021/ja00527a032 (ht t ps://doi.org/10.1021%2Fja00527a032) .

References

1. Gary H. Posner (1980). An introduction to synthesis using organocopper reagents (https://archive.org/

details/introductiontosy00posn) . New York: Wiley: Wiley. ISBN 0-471-69538-6.

2. W.A. Herrmann, ed. (1999). Synthetic Methods of Organometallic and Inorganic Chemistry. 5, Copper,
Silver, Gold, Zinc, Cadmium, and Mercury. Stuttgart: Thieme. ISBN 3-13-103061-5.

3. Christoph Elschenbroich (2006). Organometallics (3 ed.). Weinheim: Wiley-VCH. ISBN 3-527-29390-6.

4. R. C. Böttger (1859). "Ueber die Einwirkung des Leuchtgases auf verschiedene Salzsolutionen,
insbesondere auf eine ammoniakalische Kupferchlorürlösung" (https://zenodo.org/record/1427127) .
Annalen der Chemie und Pharmacie. 109 (3): 351–362. doi:10.1002/jlac.18591090318 (https://doi.org/
10.1002%2Fjlac.18591090318) .

5. Strauss, S. H. (2000). "Copper(I) and Silver(I) Carbonyls. To be or not to be Nonclassical". Journal of

the Chemical Society, Dalton Transactions. 2000: 1–6. doi:10.1039/A908459B (https://doi.org/10.103
9%2FA908459B) .
 . Light, K. M.; Wisniewski, J. A.; Vinyard, W. A.; Kieber-Emmons, M. T. (2016). "Perception of the plant
hormone ethylene: known-knowns and known-unknowns". J. Biol. Inorg. Chem. 21 (5–6): 715–728.
doi:10.1007/s00775-016-1378-3 (https://doi.org/10.1007%2Fs00775-016-1378-3) . PMID 27456611
(https://pubmed.ncbi.nlm.nih.gov/27456611) . S2CID 14399214 (https://api.semanticscholar.org/Cor
pusID:14399214) .

7. Delbaere, L. T. J.; McBride, D. W.; Ferguson, R. B. (1970). "Crystal structure of π-

cyclopentadienyl(triethylphosphine)copper(I), π-C5H5CuP(C2H5)3". Acta Crystallographica B. 26 (5):
515–21. doi:10.1107/S056774087000273X (https://doi.org/10.1107%2FS056774087000273X) .

. Posner, G. H. 2011. Substitution Reactions Using Organocopper Reagents. Organic Reactions.

22:2:253–400

9. Cairncross, Allan; Sheppard, William A; Wonchoba, Edward; Guilford, William J; House, Cynthia B;
Coates, Robert M (1979). "Pentafluorophenylcopper tetramer, a reagent for synthesis of fluorinated
aromatic compounds". Organic Syntheses. 59: 122. doi:10.15227/orgsyn.059.0122 (https://doi.org/10.
15227%2Forgsyn.059.0122) .

10. N. P. Lorenzen, E. Weiss (1990). "Synthesis and Structure of a Dimeric Lithium Diphenylcuprate:
[{Li(OEt)2}(CuPh2)]2". Angew. Chem. Int. Ed. 29 (3): 300–302. doi:10.1002/anie.199003001 (https://do
i.org/10.1002%2Fanie.199003001) .

11. Bertz, Steven H.; Cope, Stephen; Murphy, Michael; Ogle, Craig A.; Taylor, Brad J. (2007). "Rapid Injection
NMR in Mechanistic Organocopper Chemistry. Preparation of the Elusive Copper(III) Intermediate1".
Journal of the American Chemical Society. 129 (23): 7208–9. doi:10.1021/ja067533d (https://doi.org/1
0.1021%2Fja067533d) . PMID 17506552 (https://pubmed.ncbi.nlm.nih.gov/17506552) .

12. Hu, Haipeng; Snyder, James P. (2007). "Organocuprate Conjugate Addition: The Square-Planar "CuIII"
Intermediate". Journal of the American Chemical Society. 129 (23): 7210–1. doi:10.1021/ja0675346 (ht
tps://doi.org/10.1021%2Fja0675346) . PMID 17506553 (https://pubmed.ncbi.nlm.nih.gov/1750655
3) .

13. Beletkaya, I.P.; Cheprakov, A.V. (2004). "Copper in Cross Coupling Reactions: The Post Ullman
Chemistry". Coord. Chem. Rev. 248: 2337–2364. doi:10.1016/j.ccr.2004.09.014 (https://doi.org/10.101
6%2Fj.ccr.2004.09.014) .

14. For an example see: Posner, Gary H.; Whitten, Charles E. (2003). "Secondary and Tertiary Alkyl Ketones
from Carboxylic Acid Chlorides and Lithium Phenylthio(Alkyl)Cuprate Reagents:tert-Butyl Phenyl
Ketone". Organic Syntheses: 122. doi:10.1002/0471264180.os055.28 (https://doi.org/10.1002%2F0471
264180.os055.28) . ISBN 0471264229.

15. Goossen, L. J.; Deng, G; Levy, LM (2006). "Synthesis of Biaryls via Catalytic Decarboxylative Coupling".
Science. 313 (5787): 662–4. Bibcode:2006Sci...313..662G (https://ui.adsabs.harvard.edu/abs/2006Sc
i...313..662G) . doi:10.1126/science.1128684 (https://doi.org/10.1126%2Fscience.1128684) .
PMID 16888137 (https://pubmed.ncbi.nlm.nih.gov/16888137) .
1 . Reagents: base potassium carbonate, solvent NMP, catalysts palladium acetylacetonate, Copper(I)
iodide, MS stands for molecular sieves, ligand phenanthroline

17. For an example: "Addition of an Ethylcopper Complex to 1-Octyne: (E)-5-Ethyl-1,4-Undecadiene". Organic

Syntheses. 64: 1. 1986. doi:10.15227/orgsyn.064.0001 (https://doi.org/10.15227%2Forgsyn.064.000
1) .

1 . Normant, J; Bourgain, M. (1971). "Synthese stereospecifique and reactivite d' organocuivreux

vinyliques". Tetrahedron Letters. 12 (27): 2583. doi:10.1016/S0040-4039(01)96925-4 (https://doi.org/1
0.1016%2FS0040-4039%2801%2996925-4) .

19. HENDRIX, AMANDA JOY MUELLER. NOVEL METHODOLOGIES VIA THE CATALYTIC CARBOCUPRATION
OF ALKYNOATES AND THE TOTAL SYNTHESIS OF (+)-ASPERGILLIDE B (http://acumen.lib.ua.edu/conte
nt/u0015/0000001/0000446/u0015_0000001_0000446.pdf) (PDF). Retrieved January 17, 2018.

20. Daeuble, John F.; Stryker, Jeffrey M. (2001). "Hexa-μ-hydrohexakis(triphenylphosphine)hexacopper".

Encyclopedia of Reagents for Organic Synthesis. doi:10.1002/047084289X.rh011m (https://doi.org/10.
1002%2F047084289X.rh011m) . ISBN 0471936235.

21. Cox, N.; Dang, H.; Whittaker, A.M.; Lalic, G. (2014). "NHC- copper hydrides as chemoselective reducing
agents: catalytic reduction of alkynes, alkyl triflates and alkyl halides". Tetrahedron. 70 (27–28): 4219–
4231. doi:10.1016/j.tet.2014.04.004 (https://doi.org/10.1016%2Fj.tet.2014.04.004) .

22. Jurkauskas, V.; Sadighi, J. P.; Buchwald, S. L. (2003). "Conjugate addition of a,b- unsaturated
compounds catalyzad by a copper carbene complex". Org. Lett. 5 (14): 2417–2420.
doi:10.1021/ol034560p (https://doi.org/10.1021%2Fol034560p) . PMID 12841744 (https://pubmed.nc
bi.nlm.nih.gov/12841744) .

23. Otaka, A.; Watanabe, H.; Mitsoyama, E.; Yukimasa, A.; Tamamura, H.; Fujii, N. Synthesis of (Z)-
fluoroalkene isosteres utilizing organocopper- mediated reduction of gama, gamma- α,β - enoates.
Tetrahedron Lett. 2001, 42, 285-287.

24. Okada, M.; Nakamura, Y. Sago, A.; Hirokawa, H.; Taguchi, T. Stereoselective cosnstruction of
functionalized (Z)- fluoroalkenes directed to o- depsipeptide isosteres. Tetrahedron Lett. 2003, 43, 5845-
5847.

25. Otaka, A.; Watanabe, H.; Yukimasa, A.; Oishi, S.; Tamamura, H.; Fuji, N. New access to α- substituted
(Z)-fluoroalkene dipeptide isosteres utilizing organocopper reagents under redoctive-oxidative alkylation
(R-OA) conditions. Tetrahedron Lett. 2001, 42, 5443-5446

2 . Yamamoto, H.; Marouka, K. (1980). "Novel N-alkylation of amines with organocopper reagents". J. Org.
Chem. 45 (13): 2739–2740. doi:10.1021/jo01301a048 (https://doi.org/10.1021%2Fjo01301a048) .

27. Muller, A.J.; Jennings, M.P. Vicinal Functionalization of propionilate Esters via Tandem Catalytic
Carbocupration-Mukaiyama Aldol Reaction sequence. Org. Lett. 2008, 10, 1649-1652
Retrieved from
"https://en.wikipedia.org/w/index.php?
title=Organocopper_compound&oldid=102906741
5"

Last edited 23 days ago by JAH292

Content is available under CC BY-SA 3.0 unless

otherwise noted.