Lithium cyclopropyl cuprate

Metallo 2-vinylcyclopropanes were introduced independently as a tool for the efficient preparation of 1,2-divinylcyclopropane skeletons in 1976 by the three groups mentioned above ". Either 2-vinylcyclopropyl lithium addition to 3-alkoxyenones " followed by acid treatment will lead to the desired rearrangement precursors (equation 166), or the corresponding cyclopropyl cuprates will add to j5-iodoenones and electrophilic acetylenes " forming directly divinylcyclopropanes (equation 167). 

Allylation of a-thio-35), a-seleno-35) and a-silyl- 35,77) cyclopropyllithiums was not very successful35) but addition at —78 °C of 0.5 equivalent of copper (I) iodide-dimethylsulfide complex 35,106, W7> prior to the allylhalide leads 35,106,107) to a very high yield of homoallyl cyclopropyl sulfides or selenides (Scheme 24). Similar observations have been made on cyclobutyl derivatives3S). It is not clear at present whether a cuprate is involved in the process but we have evidence ( Se-NMR) that a new species is transiently being formed, at least in the seleno series. The synthesis of homoallyl cyclopropylsilanes was also reported 78) and involves the allylation of a postulated cuprate formed by the addition of lithium dibutyl cuprate to a-lithiocyclopropylsilane (Scheme 26). 

Most reactions have been performed using lithium cyclopropyl(phenylsulfanyl)cuprate, but the homocuprate lithiumdicyclopropylcuprate complexed with dimethyl sulfide has also been used. ° Generally the yields are very good, in most cases above 80%. 

CONJUGATE ADDITION Alkylmethyl-magncsiocuprates. 2-Carboethoxyl-benzyl phenyl sulfoxide. Cyanodiethyl-aluminum chloride. 1-Cyclopropyl-l-tiimethylsilyloxyethylene. Lithium 1,3-butadiene-l-olate. Lithium dimethyl-cuprate. Magnesium ethyl malonate. Potassium carbonate. Tri-n-butyl-stannyllithium. Trimethylzinclithium. 

CYCLOPENTANE ANNELATION Lithium phenylthio(cyclopropyl)cuprate. 

One general method for acyl silane synthesis particularly successful for a-cyclopropyl examples (and even an a-cyclobutyl example) involves treatment of acid chlorides with lithium tetrakis(trimethylsilyl) aluminum or lithium methyl tris(trimethylsilyl) aluminium and cuprous cyanide (vide supra, Section III.A.3)77. For example, cyclopropyl acyl silane (23) was obtained in 89% yield by this process. Improved procedures use lithium t-butyldimethylsilyl cuprate78 and a dimethylphenylsilyl zinc cuprate species79,80 as reagents. 

Lithium (cyelopropyl)(phenylthio) cuprate (l).27 This cuprate is prepared by addition of cyclopropyllithium to phenylthiocopper in THF at -78- — 20°. It converts /J-iodo enones (2) into /1-cyclopropyl enones (3) in excellent yield, even when 2 is substituted at the a-position by a methyl group. The products are useful because they rearrange when heated to annelated cyclopentenes (4 and/or 5). The rearrangement is particularly efficient when R = H, and results in 5 as the major product ( 85% yield). 

Cyclopropyl ketones are formed on addition of an equimolar amount of lithium dimethylcuprate to the acid chlorides of cyclopropanedicarboxylates, but with excess cuprate a ring-opening reduction to pentane-l,S-diones takes place. ... 

Modhephene, 34, was the first isolated propellane natural product. As such, the Weiss-Cook reaction was the perfect method for its construction. The process began with the condensation of 2 with diketone 27. Standard conditions for decarboxylation produced the core scaffold 28. Hydrogenation of the mono-enol phosphate afforded the monoketone 29. The cyclopropyl derivative 30 was prepared by copper-catalyzed decomposition of a diazoketone. gem-Dimethylation to generate 31 preceded carboxylation and esterification to afford the advanced intermediate 32. Cuprate-induced cyclopropane ring opening and methylation of the 3-ketoester introduced the final carbon atoms giving rise to 33. Lithium iodide induced decarboxylation preceded reduction of the ketone followed by dehydration with Martin s sulfurane, thus producing 34. 

LITHIUM 1-METHYL-2-(2-METHYL-1-( )-PROPENYL)CYCLOPROPYL(PHENYLTHIO)CUPRATE... 

Lithium 1 -Methyl- 2 - (2 -methyl-1 - ( -propenyl) cyclopropyl (phenylthio) -cuprate... 

Table 1 Lithium 1 methyl-2-(2-methyl-l-(.Q-propenyl)cyclopropyl (phei lthio)cuprate and related reagents...

Lithium l-Methyl-2-(2-methyl 1 propenyl)cyclopropyl(phenylthio)cuprate 330 University of Bristol, Bristol UK... 

The low ionic character of the aluminium-silicon bond has been cleverly utilized to develop a very mild, general and effective synthesis of acyl silanes, successful for aliphatic, aromatic, heteroaromatic, a-aUcoxy, a-amino and even a-chiral and a-cyclopropyl acyl sUanes. Acyl chlorides are treated with lithium tetrakis(trimethylsilyl)aluminium or lithium methyl tris(trimethylsilyl) aluminium in the presence of copper(I) cyanide as catalyst to give the acyl silanes in excellent yields after work-up. Later improvements include the use of 2-pyridinethiolesters in place of acyl halides, allowing preparation of acyl silanes in just a few minutes in very high yields indeed (Scheme 9) °, and the use of bis(dimethylphenylsilyl) copper lithium and a dimethylphenylsilyl zinc cuprate species as nucleophiles. 

Conjugate Addition Reactions.—The use of polymer-bound dialkylcuprates gives comparable or higher than normal yields in the conjugate addition to enones the major advantage lies in the ease of work-up. The mechanism of conjugate addition of cuprates and the mechanism and stereochemistry of the addition of lithium dimethylcuprate to jS-cyclopropyl-substituted enones have been reported. 

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