Carbonyl compounds reaction with organocuprates

Ethynyl carbinols (propargylic alcohols) such as 134 (Scheme 2.58) represent another important group of oxidation level 3 compounds. Their preparation involves nucleophilic addition of acetylides to the carbonyl group, a reaction that is nearly universal in its scope. Elimination of water from 134 followed by hydration of the triple bond is used as a convenient protocol for the preparation of various conjugated enones 135. Easily prepared O-acylated derivatives are extremely useful electrophiles in reactions with organocuprates, which proceed with propargyl-allenyl rearrangements to furnish allene derivatives 136. 

The stereoselective 1,4-addition of lithium diorganocuprates (R2CuLi) to unsaturated carbonyl acceptors is a valuable synthetic tool for creating a new C—C bond.181 As early as in 1972, House and Umen noted that the reactivity of diorganocuprates directly correlates with the reduction potentials of a series of a,/ -unsaturated carbonyl compounds.182 Moreover, the ESR detection of 9-fluorenone anion radical in the reaction with Me2CuLi, coupled with the observation of pinacols as byproducts in equation (40) provides the experimental evidence for an electron-transfer mechanism of the reaction between carbonyl acceptors and organocuprates.183... 

Organocuprate(I) reagents like R2CuLi readily react with organic electrophiles (E +), for example, alkyl halides or a, 3-unsaturated carbonyl compounds (Scheme 12.5).15 On the other hand, there are only a few reports where one could assume a participation of organoargentate16 or organoaurate17 intermediates in organic reactions. 

In addition to their reactions with acid chlorides, epoxides, and a,P-unsaturated carbonyl compounds (Sections 20.13-20.15), organocuprate reagents (R2CuLi) also react with organic halides R X to form coupling products R-R that contain a new C-C bond. Only one R group of the organocuprate is transferred to form the product, while the other becomes part of RCu, a reaction by-product. 

Reaction of an a,P-unsaturated carbonyl compound with an organocuprate reagent... 

Conjugate addition is also a feature of the reaction of organocuprates with a,p-acetylenic carbonyl compounds. By conducting the reaction at —78 °C, high yields of cis addition compounds can be obtained (1.163). This allows the stereocontrolled... 

The reaction of carbon nucleophiles with ketones or aldehydes proceeds by acyl addition, as described in Chapter 18. The reaction of carbon nucleophiles with acid derivatives proceeds by acyl substitution, as described in Chapter 20. Carbon nucleophiles included cyanide, alkyne anions, Grignard reagents, organolithium reagents, and organocuprates. Alkyne anions are formed by an acid-base reaction with terminal alkynes (RC=C-H RCsCr). In this latter transformation, it is clear that formation of the alkyne anion relies on the fact that a terminal alkyne is a weak carbon acid. Other carbon acids specifically involve the proton on an a-carbon in aldehydes, ketones, or esters. With a siiitable base, these carbonyl compounds generate a new type of carbon nucleophile called an enolate anion. 

The problem of 1,2 versus 1,4 addition persists with most nucleophiles in their reactions with a,P-unsaturated carbonyl compounds. However, one class of carbanion reagent gives almost exclusively 1,4 addition the organocuprates. These reagents were introduced in Chapter 15 (Section 15.6), where they reacted with alkyl halides to give coupling products. 

Enones.—The synthetic utility of organocuprates has been reviewed. House has presented a correlation between the conjugate addition of lithium dimethylcopper to a -unsaturated carbonyl compounds and their polarographic reduction potentials such a correlation is compatible with the first step of the mechanism (Scheme 100) proposed for this reaction. In conjunction with empirical rules for the estimation (with an accuracy of 0.1 V) of the reduction potentials of such unsaturated compounds, this... 

Complex 69, formed via n-complexation of an organocuprate with an unsaturated carbonyl compound, is the common starting point in both pathways (Scheme 26). jr-Complexation is followed by either (1) a formal oxidative addition to the p-carbon of the carbonyl compound to afford o-complex 70 (Cu(lll)-intermediate) that after a reductive elimination step affords the it-adduct 72 or (2) a carbocupration reaction affording compound 71 that upon rearrangement leads to jr-adduct 72 [105-108]. 

There is also a correlation between the reduction potential of the carbonyl compound and the ease of reaction with cuprate reagents. The more easily reduced, the more reactive is the compound toward organocuprate reagents. Compounds such as a,/3-unsaturated esters and nitriles which are not as easily reduced as a,j3-unsaturated ketones do not react readily with simple alkyl cuprates even though they are good acceptors in conjugate addition reactions involving other types of nucleophiles (Michael reactions). 

Regioselective addition to a,p-unsaturated carbonyl compounds is an age-old pursuit, and reactions selective for either 1,2- or 1,4-addition are ubiquitous in modern organic synthesis. Nucleophile character (hard versus soft) and solvent polarity (contact versus separated ion pairs),among other factors, contribute to the reaction outcome. The typical reaction of Grignard reagents with enones results in mixtures of 1,2- and 1,4-addition products. From their earliest inception, Cu(i) catalysts and reactants have been used to effect selective 1,4-addition in this archetypical transformation of organocuprates. ... 

---