Organocopper reagents formation

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. 

With the reagent PhCu in the presence of the additives BF3 and PBU3, ees of up to 95% were obtained, while values of up to 85% were achievable with a vinyl copper reagent. Chiral dienic acetals have also been studied three regioisomeric products could be obtained in this case as the result of Sn2, Sn2, or Sn2" attack of the organocopper reagent [25]. Mixtures were indeed obtained with alkyl copper reagents, but PhCu BFs resulted in formation of only the Sn2 and Sn2" products, with selectivity for the latter (Scheme 8.12). 

The formation of chiral allenes from centrochiral propargylic alcohol derivatives and organocopper reagents, e.g., the conversion of (/ )-l-cthynylpentyl acetate to allene 928. 

The selective formation of 5-hydroxy-2,2-dimethylch romenes instead of the usual 7-hydroxy isomer has been accomplished with organocopper reagents <79JCS(Pl)201). Olivetol bis(tetrahydropyranyl ether) (61) is- selectively metallated at C-2 and the resulting homocuprate (62) reacts with 3-acetoxy-3-methylbut-l-yne to yield 5-hydroxy-2,2-dimethyl-7-pentylchroipene (63 Scheme 7). 

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. 

The conjugate addition of organocopper reagents to ot,(3-alkynic esters, ketones, aldehydes and acids is a useful method for the preparation of various tri- and tetra-substituted alkenes,87 although addition to aldehydes is less common.88 Use of a vinylcuprate results in the formation of a conjugated dienone, which further highlights the importance of this methodology (equation 43 ).87... 

A stereoselectivity dependence on the cuprate was also reported in the -alkylation of y-substituted acyclic enoates (Scheme 17).101 The trans isomer (41) gave preferential formation of the anti isomer (42), regardless of the organocopper reagent employed. When the cis isomer (43) was treated with... 

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