Organocopper reagents alkylations

The simplest case is the substitution of a halogen at a saturated carbon atom by an alkyl group. Organocopper reagents exhibit strong carbanionic capacity, and do attack ester groups only slowly (D.E. Bergbreiter, 1975). Ketones, however, should be protected. The relative re-... 

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). 

For use of other organocopper reagents in converting carboxylic acid chlorides to ketones, see G. H. Posner and C. E. Whitten, Tetrahedron Lett., 1815 (1973) G. H. Posner, C. E. Whitten, and P. E. McFarland, J. Amer. Chem. Soc., 94, 5106 (1972). For a recent report on direct and convenient preparation of lithium phenylthio (alkyl)-cuprate reagents, see G H Posner, D J Brunelle, and L. Sinoway, Synthesis, 662 (1974). 

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. 

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

Organocopper chemistry also provides a straightforward synthesis through a special alkylation procedure (Scheme 7-22). An organocopper reagent, generated in situ from equimolar amounts of co-side chain vinyl lithium, Cul, and... 

The organocopper reagents prepared in this way cleave epoxides in high yield with substitution of the alkyl group at the less hindered site. This cleavage has been used to effect intramolecular cyclization (second example). 

Scheme 2.12. Alkylation of organocopper reagents derived from Grignard compounds.

This reaction can also be applied to the preparation of heterocyclic organocopper reagents such as 77 from readily available secondary alkyl iodides. Ring-closure in this case is catalyzed by Ni(acac)2 rather than by Pd(0), affording new heterocyclic molecules such as 78 (Scheme 2.26) [55]. These cyclization reactions are key steps in the preparation of such natural products as (-)-methylenolactocin 79 [57] and methyl epijasmonate 80 [58] (Scheme 2.27). 

Scheme 3.34. Alkylation or arylation of amines by treatment of organocopper reagents with amines [119].

Obviously, the nature of the organocopper reagent is an important factor with respect to the stereochemical outcome of the cuprate addition. This is nicely illustrated for the cuprate addition reaction of enoate 75 (Scheme 6.15). Here, lithium di-n-butylcuprate reacted as expected by way of the modified Felkin-Anh transition state 77 (compare also 52), which minimizes allylic A strain, to give the anti adduct 76 with excellent diastereoselectivity [30]. Conversely, the bulkier lithium bis-(methylallyl)cuprate preferentially yielded the syn diastereomer 78 [30, 31]. It can be argued that the bulkier cuprate reagent experiences pronounced repulsive interactions when approaching the enoate system past the alkyl side chain, as shown in transition state 77. Instead, preference is given to transition state 79, in which repulsive interactions to the nucleophile trajectory are minimized. 

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