[57428-12-3]  · C7H13CuO2  · 3,3-Diethoxy-1-propen-2-ylcopper  · (MW 192.72)

(reagent for the synthesis of a-methylene lactones;1 1,2-addition of the 2-substituted acrolein moiety;2 1,4-addition of the 2-substituted acrolein moiety3)

Alternate Name: 1-(diethoxymethyl)vinylcopper.

Preparative Method: by reaction of 2-lithio-3,3-diethoxy-1-propene and copper iodide in THF at -55 °C.

Handling, Storage, and Precautions: sensitive to air and moisture; decomposes above -20 °C. Use in a fume hood.

The discovery of natural products containing the a-methylene lactone moiety stimulated the development of several 2-metallo acrylate and acrolein derivatives. Marino and Farina prepared 3,3-diethoxy-1-propen-2-ylcopper from the corresponding functionalized vinyl lithio reagent and 1 equiv of Copper(I) Iodide in THF at -55 °C and examined the reactivity of this reagent with cyclohexene monoepoxide.1 The neutral copper reagent gave predominantly the anti 1,4-addition product in good yield. Formation of the homocuprate reagent from copper iodide using 2 equiv of the lithio anion gave a more reactive reagent that led to the anti 1,2-adduct as the major product. Mixed cuprates employing the nontransferable t-butylacetylene or cyano ligands were also prepared; the lower order cyanocuprate gave the lowest yields in the addition reaction, but was as selective for the 1,4-addition product as the neutral copper reagent (eq 1). The regioselectivity for 1,2-addition was enhanced using the homocuprate and carrying out the reaction in ether instead of THF. After hydrolysis of the acetal, the 1,2- and 1,4-adducts were stereospecifically converted to trans- or cis-a-methylene lactones, respectively, by oxidation to the acrylate and subsequent ring closure (eqs 2 and 3).

Grieco and co-workers also compared the reactivity of the 3,3-diethoxy-1-propen-2-ylcopper reagent and the thiophenoxy mixed cuprate in reactions with allyl halides (eq 4).2 Both the neutral copper and cuprate reagents appeared to be specific for reaction with allylic halides and did not react with either benzyl bromide or 1-iodo-trans-oct-1-ene. Interestingly, the thiophenoxy mixed cuprate provided the 1,4-addition product with cyclohexenone (eq 5), while the neutral copper reagent resulted only in 1,2-addition to cyclohexenone (eq 6).

The reactivity of the neutral copper reagent toward carbonyls was also employed by Roush and Peseckis in the synthesis of 2-substituted acrolein derivatives, which underwent intramolecular Diels-Alder reaction to provide angularly oxygenated perhydroindenes.4 Boeckman and Ramaiah observed better results in 1,4-addition reactions using the t-butylalkynic mixed cuprate reagent.3 Lower yields of 1,4-addition were observed in reactions with b-substituted cyclohexenones or sterically hindered enones such as 4-t-butylcyclohexenone. It was also indicated that 3,3-diethoxy-1-propenylcuprate reagents did not react with primary or secondary alkyl bromides, vinyl bromides, or iodides; the major product isolated in attempted alkylation reactions was the 1,4-diene resulting from oxidative dimerization.

Conjugate addition reactions of the homocuprate derived from 2-lithio-3,3-diethoxy-1-propene have been reported in the synthesis of (+)-hanegokedial (eq 7),5 and in an approach to ciliarin (eq 8).6 1,4-Addition of the cuprate to the cycloheptenone derivative, with in situ trapping of the derived enolate with gaseous Formaldehyde, led to the a,b-dialkylated product in good yield. The 1,4-addition stereochemistry was controlled by the cyclopropyl substituent, while the alkylation of the enolate led to a mixture of isomers. In the approach to ciliarin, stereospecific conjugate addition to the unsaturated lactone was achieved using in situ Chlorotrimethylsilane. The chemistry of 2-metallo acrylates7 and b-substituted acrylates8 has also been developed. These functionalized cuprates exhibit atypical cuprate reactivity, favoring 1,2- over 1,4-addition in reactions with enones; however, reactions with acid chlorides provide a,a-dienyl ketones in good yield.9

Related Reagents.

Lithium Bis(3,3-diethoxy-1-propen-2-yl)cuprate; Lithium (3,3-Diethoxy-1-propen-2-yl)(phenylthio)cuprate; Lithium Divinylcuprate; Vinylcopper.

1. (a) Marino, J. P.; Farina, J. S. JOC 1976, 41, 3213. (b) Marino, J. P.; Farina, J. S. TL 1975, 3901.
2. Grieco, P. A.; Wang, C-L. J.; Majetich, G. JOC 1976, 41, 726.
3. Boeckman, Jr., R. K.; Ramaiah, M. JOC 1977, 42, 1581.
4. Roush, W. R.; Peseckis, S. M. JACS 1981, 103, 6696.
5. Taylor, M. D.; Smith, III, A. B. TL 1983, 24, 1867.
6. Caine, D.; Venkataramu, S. D.; Kois, A. JOC 1992, 57, 2960.
7. Marino, J. P.; Floyd, D. M. JACS 1974, 96, 7138.
8. Marino, J. P.; Linderman, R. J. JOC 1983, 48, 4621.
9. Marino, J. P.; Linderman, R. J. JOC 1981, 46, 3696.

Russell J. Linderman

North Carolina State University, Raleigh, NC, USA

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