Copper(I) Iodide-Tributylphosphine1

[CuI{(n-Bu)3P}]4

[28132-72-1]  · C48H108Cu4I4P4  · Copper(I) Iodide-Tributylphosphine  · (MW 1571.08)

(promoter for conjugate addition of alkyl (vinyl, etc.) lithium reagents to a,b-unsaturated ketones and related compounds; preformed copper-phosphorus compound (occasionally generated in situ) to stabilize and solubilize organocoppers whose conjugate addition is facilitated by the use of a phosphorus auxiliary;1 also used to effect oxidative coupling2)

Alternate Name: tetrakis[iodo(tri-n-butylphosphine)copper(I)].

Physical Data: mp 75 °C; d (at 78 °C) 1.390 g cm-3; decomposition to CuI and tributylphosphine at 200-210 °C/0.01 mmHg.

Solubility: sol chloroform, benzene, toluene, and ethyl ether; moderately sol ethanol, 2-propanol, and water.

Preparative Methods: generated in situ or prepared either via the reaction of Copper(I) Iodide with freshly distilled Tri-n-butylphosphine3a or with copper(I) iodide dissolved in saturated aqueous Potassium Iodide and stirred with tri-n-butylphosphine.3b

Purification: may be recrystallized from ethanol-2-propanol and air dried.3

Analysis of Reagent Purity: decomposed by heating with Na2CO3 and residue treated with HNO3; dissolved in water, sulfuric acid added, and Cu determined by electrolytic reduction;3 1H NMR spectra4 and electronic absorption and emission spectra have been studied.5

Handling, Storage, and Precautions: toxicity data unavailable. Unless refrigerated it decomposes in several days at rt to a viscous syrup;3 use in a fume hood.

Conjugate Addition.

Early in the study of the reactions of organometallic reagents with a,b-unsaturated ketones it became clear that the reaction of organomagnesium compounds could be diverted from the normal path of 1,2-addition to favor the abnormal path of 1,4-addition by the presence of a small amount of a copper compound.6,7 Thus trans-3-penten-2-one in ether (in a flowing stream reactor) gave, in >99% conversion, <1% conjugate addition on reaction with Methyllithium to yield 2-methyl-3-hexen-2-ol. However, under the same conditions, when an organocopper reagent was preformed by adding 1 mole of n-Bu3PCuI to 1 mole of MeLi, again in >99% conversion, there was >99% conjugate addition in the product to form 4-methyl-2-pentanone (eq 1).7

In a continuation of this work8 the tri-n-butylphosphine complex of copper(I) iodide and Lithium Dimethylcuprate were compared to the corresponding trimethyl phosphite complex (see Copper(I) Iodide-Trimethyl Phosphite) in the addition reactions to 5-methyl-2-cyclohexenone (eq 2), 3-methyl-2-cyclohexenone (eq 3), and 5,5-dimethyl-2-cyclohexenone (eq 4).

For the first case (eq 2), both reagents gave predominately trans product (trans:cis = 98:2), but the reaction with the tri-n-butylphosphine complex produced a 34% yield of products while the trimethyl phosphite complex yielded product in 73-87% yield (as a function of the amount of Lithium Iodide added or of tertiary phosphine ligand present).9 In both the second and third cases (eqs 3 and 4) the two complexes gave approximately the same yields.8 Shortly thereafter, conjugate addition of the corresponding vinyl reagent to yield g,d-unsaturated ketones was reported.10

Conjugate addition reactions of both lithium11-15 and magnesium16 alkyls to substituted11-14 and unsubstituted15,16 cyclopentenones followed by aldol type condensations11,14 or alkylations15,16 (if a-substitution was not present initially) have served as entries into prostaglandin synthesis. Additionally, the same process has served as a key step in the syntheses of terpenes,17 carbohydrates,18 pyridine derivatives,19 N-enoylsultams (producing b-silylcarboxyl derivatives20 or alkyl substituted derivatives with good stereoface differentiation),21 macrolides,22 acetals,23 and silyl enol ethers.24

Oxidative Coupling.

It was early reported2 that the dialkylcuprate (e.g. Lithium Di-n-butylcuprate) prepared by reaction of one equivalent of tetrakis[iodo(tri-n-butylphosphine)copper] in THF at -78 °C with n-Butyllithium on oxygenation produced ca. 84% octane. Subsequently, vinyl,25-28 aryl,29,30 and other alkyl31,32 couplings have been effected, some with polymer supported cuprate33 and one to a thioester to facilitate an otherwise difficult Grignard reaction.34 Alkyl coupling to phosphorus in cyclophosphazines (NPX2)3&b;or&b;4 (X = Cl, F) can also be brought about in the presence of the title reagent.35

Rearrangements and Unusual Reactions.

Regioselective ring opening of b-propiolactones to yield b-substituted propanoic acids has been observed,36 as has an unusually gentle cyclization of an azetidinone derivative to a penem (eq 5).37 In the presence of a strained carbocycle the reagent has been found to behave much like a Lewis acid, yielding rearranged alkene (eq 6).38

Other Transformations and Limitations.

Organosamarium species have been generated by in situ transmetalation with the reagent.39 It is claimed that solutions of highly reactive zerovalent copper, useful for oxidative addition to alkyl, vinyl, and aryl halides, are easily prepared by Lithium Naphthalenide reduction of the title reagent and similar species.40 Superior results in prostaglandin synthesis have recently been obtained by substituting higher order cuprates.41 Unlike other organometallic reagents, tetrakis[iodo(tri-n-butylphosphine)copper(I)] fails to react with arenesulfonyl fluorides to produce sulfones.42

Related Reagents.

Copper(I) Iodide-Tributyl Phosphite; Copper(I) Iodide-Triethylphosphine-Lithium Naphthalenide; Copper(I) Iodide-Triethyl Phosphite; Copper(I) Iodide-Trimethyl Phosphite; Lithium Diethylcuprate-Tributylphosphine.


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Linda M. Mascavage

Beaver College, Glenside, PA, USA

David R. Dalton

Temple University, Philadelphia, PA, USA



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