Organocopper reagents reactivity

The mechanism of conjugate addition reactions probably involves an initial complex between the cuprate and enone.51 The key intermediate for formation of the new carbon-carbon bond is an adduct formed between the enone and the organocopper reagent. The adduct is formulated as a Cu(III) species, which then undergoes reductive elimination. The lithium ion also plays a key role, presumably by Lewis acid coordination at the carbonyl oxygen.52 Solvent molecules also affect the reactivity of the complex.53 The mechanism can be outlined as occurring in three steps. 

Recent theoretical developments such as DFT methods, can of course provide more advanced and precise understanding of these interactions. Hence, Nakamura et al. have recently used computational methods to explain and forecast structure-reactivity relationships in organocopper reagents (Chapt. 10) [28, 43]. 

Scheme 10.1. Nucleophilic reactivities of organocopper reagents. R = sp, sp carbon anionic centers X, Y = halogen, etc.

In many cases a Lewis acid has been added to a cuprate to enhance its reactivity with an enone, but there are also examples for which the Lewis acid-organocopper reagents do not work well, (Scheme 10). Reaction of the bicyclic enonate (24) with Me2CuLi led to smooth conjugate addition,71 but the use of either Me2CuLiBF3 or MeCuBFj resulted in formation of a dark resinous material. It is often difficult to predict when the reaction will go astray, but it should be recognized that a Lewis acid-cuprate complex is not always an effective solution to a reactivity problem. 

In the total synthesis of mevinolin,122 a stereoselective conversion of (57) into (58) was called for. Several organocopper reagents were examined, but it was MeCu-BFa which exhibited die highest selectivity (Scheme 26). The reason for the selectivity is not obvious, but the results do indicate that there can be significant differences between the reactivity profile of the various organocopper reagents available. 

---