Organocopper reagents 1.2- additions

CONJUGATE ADDITION OF ORGANOCOPPER REAGENTS TO a,p-UNSATURATED CARBONYL COMPOUNDS... 

Witli tlie reagent PbCu in tlie presence of tlie additives BF and PBu- , ees of up to 9 596 were obtained, wb de values of up to 8 596 were acliievable witli a vinyl copper reagent. Chiral dienic acetals have also been studied tliree regioisomeric products could be obtained in tliis case as tlie result of Su2, Su2, or Su2" attaclt of tlie organocopper reagent [25]. Mixtures were indeed obtained witli alKyl copper reagents, but PbCu-BF resulted in fotniation of only tlie S 2 and Su2" products, witli selectivity for tlie latter fSclieme 8.12). 

With respect to the nucleophilic addition of organocopper reagents, a sharp contrast between the rigid isopropylidene glyceraldehyde and its open-chained analog, 2,3-bis(benzyloxy)propanal. was observed (compare Tables 15 and 16). With the isopropylidene-protected aldehyde a high syn diastereoselectivity could only be obtained when tetrahydrofuran was used as reaction solvent, and the diastereoselectivity dropped considerably in diethyl ether. In contrast, the latter solvent allows excellent syn selectivities in additions to the dibenzyl-protected glyceraldehyde81. On the other hand, tetrahydrofuran yields better results than diethyl ether in the... 

In conclusion, there are only a few examples of conjugate additions with optically active organocopper reagents in which the copper is directly attached to the stereogenic center. There is still room for extensive investigation of this field. 

There is generally little or no competition from 1,2 addition (to the C=0). However, when R is allylic,l,4 addition is observed with some substrates and 1,2 addition with others. The compound R2CuLi also add to a,P-unsaturated sulfones but not to simple aP-unsaturated nitriles. Organocopper reagents RCu (as well as certain R2CuLi) add to ocP-unsaturated and acetylenic sulfoxides. ... 

For the addition of organocopper reagents to alkynes and conjugated dienes, see 15-23. 

Recently, enantiomerically pure vinylic sulfoximines have been shown to undergo effective and highly stereocontrolled conjugate addition of hydrocarbon groups using organocopper reagents . 

Tandem conjugate addition-alkylation has proven to be an efficient means of introducing groups at both a- and (3-positions at enones.307 As with simple conjugate addition, organocopper reagents are particularly important in this application, and they are discussed further in Section 8.1.2.3. 

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. 

Scheme 8.2. Conjugate Addition Reactions of Organocopper Reagents...

Scheme 8.3. Tandem Conjugate Addition-Alkylation Using Organocopper Reagents... 

Enantioselective Reactions of Organocopper Reagents. Several methods have been developed for achieving enantioselectivity with organocopper reagents. Chiral auxiliaries can be used for example, oxazolidinone auxiliaries have been utilized in conjugate additions. The outcome of these reactions can be predicted on the basis of steric control of reactant approach, as for other applications of the oxazolidinone auxiliaries. 

Addition of organocopper reagents to imine derivatives can readily afford functionalized amine derivatives. Three recent examples are shown below (Equations (129) and (130) Scheme 102).498,498a,498b In these cases, iminium ions are employed as an activated imine. 

Conjugate additions to enals and enones.1 ClSi(CH,)3/HMPT markedly accelerates the Cu(I)-catalyzed conjugate addition of Grignard reagents to enals, enones, and unsaturated esters. The conjugate addition of organocopper reagents is also facilitated. 

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