Lithium dimethylcuprate reactions with ketones

Lithium dimethylcuprate reacts with [(Tp )(CO)W( n2-PhCsCMe)(I)] to give [(Tp )(CO)W(Ti2-PhCsCMe)(Me)]. This methyl conq>lex can be protonated in the presence of ketones or aldehydes to afford cationic T -ketone or t] -aldehyde conqtlexes. Reaction of... 

The conj ugate addition of lithium dimethylcuprate and other organoeopper reagents to a,/ -unsaturated ketones is a reaction which has had wide application and which has been fairly well studied.6 In order that the positional specificity which has been conferred upon the enolate anions generated by such additions might be maintained, these intermediates have been intercepted with acetic anhydride,6 chlorotrimethylsilane, and diethyl phosphorochloridate.4 8... 

Indeed, in diethyl ether, lithium dimethylcuprate usually reacts with the a-enone group to give a methyl-substituted bromo ketone. Addition of hexamethylphosphoric triamide (HMPT), however, slows down this reaction to such an extent that displacement of the bromo substituent takes place [698], Another remarkable example of the influence of HMPT on chemoselectivity is the reaction of an arsonium ylide, Ph3As= CH-CH=CH-Ph, with benzaldehyde in tetrahydrofuran solution, yielding either an epoxide (in THE) or an alkene (in THF/HMPT) [699],... 

A 1,3-dibromo ketone was also reductively cyclized with lithium dimethylcuprate in diethyl ether, containing furan, to form tetramethylcyclopropanone by a two-electron reduction and subsequent addition of the cuprate across the reactive carbonyl function to give 34. Side products include 2,2,4-trimethylpentan-3-one and the [3-f4] cycloaddition product of the cyclopropanone with furan. An ethereal medium is a requirement, since the same reaction in pentane at — 50°C did not lead to cyclopropane derivatives. More detailed information on the in situ generation of cyclopropanenes and subsequent addition of nucleophiles is given in Section 1.1.3.3. 

The earlier part of the synthesis of (—)-phytocassane D (49) is shown in Figure 2.34. The starting material was (ft)-Wicland-Mieschcr ketone (A) prepared by the well-known organocatalytic Robinson annulation reaction. To enhance the enantiomeric purity of A, the corresponding acetal B was recrystallized from ether to give (R)-B of >95% ee. This was converted to C. Then, the second Robinson annulation furnished D, which yielded the isomeric ketone F via E. Methylation of F with lithium dimethylcuprate... 

A convenient synthesis of (— )- xo-brevicomin (87) utilizes a radical chain reaction of methyl vinyl ketone with (45, 5R)-4-benzyloxymethyl-5-iodomethyl-2,2-dimethyl-l,3-dioxo-lane (209), prepared by treating the (R,R)-tartaric acid derivative 141 with triphenylpho-sphonium iodide in the presence of imidazole. Adduct 215, after acidic hydrolysis of the isopropylidene protecting group, furnishes the bicyclic acetal 216. Subsequent debenzylation and tosylation followed by methylation with lithium dimethylcuprate provides 87 in an overall yield of 17% from (R,R)-tartaric acid. The optical purity of 87 corresponds to greater than 99% ee (Scheme 50). Carrying out a similar series of transformations with ( S,5)-tartaric acid leads to ( + )-exo-brevicomin (90) [78]. 

Methoxyallene has previously been used to prepare acetylenes via its reaction with Grignard reagents, in the presence of copper(i) halides.The use of preformed dialkylcuprates, however, gave the vinyl ethers instead. The E Z ratio varied with the substituent but it is difficult to explain why the difference is observed.Methoxyallene has also been converted into its vinyl anion and used in the synthesis of dihydrofurans and furans in an analogous way to ordinary vinyl ethers.Similarly allenic cuprates have been prepared and used in the synthesis of allenes and allenic pheromonessome examples are outlined in Scheme 58. The addition of lithium dimethylcuprate to allene phosphine oxides and allenic ketones was interpreted in terms of a 1,2- rather than a 1,4-addition process, in contrast to a/3-unsaturated... 

Ketones are converted to dibromomethylene derivatives. These intermediates can be transformed to isopropylidene compounds by reaction with Lithium Dimethylcuprate and lodomethane (eq 14). No racemization was reported for the chain extension... 

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