Professional Documents
Culture Documents
Organocopper Compounds
Organocopper Compounds
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.
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]
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−).
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]
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.
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]
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]
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
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
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:
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 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
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.
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) .
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
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.
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"