Zinc reagents, conjugate addition

Recently, attempts were made to replace the air- and moisture-sensitive zinc and magnesium reagents in the copper-catalysed asymmetric conjugate addition, with... 

Scheme 2.23 provides some examples of conjugate addition reactions. Entry 1 illustrates the tendency for reaction to proceed through the more stable enolate. Entries 2 to 5 are typical examples of addition of doubly stabilized enolates to electrophilic alkenes. Entries 6 to 8 are cases of addition of nitroalkanes. Nitroalkanes are comparable in acidity to (i-ketocslcrs (see Table 1.1) and are often excellent nucleophiles for conjugate addition. Note that in Entry 8 fluoride ion is used as the base. Entry 9 is a case of adding a zinc enolate (Reformatsky reagent) to a nitroalkene. Entry 10 shows an enamine as the carbon nucleophile. All of these reactions were done under equilibrating conditions. 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

As recent examples of copper-catalyzed asymmetric conjugate addition of organo-zinc reagents (a) Mizutani, H. ... 

Scheme 8.3. Conjugate Addition and Alkylation Reactions of Mixed Copper-Zinc Reagents...

The Cu(I)-catalysed asymmetric conjugate addition of dialkyl zinc reagents to 3-nitrocoumarins 45 gives high yields of 3,4-dihydrocoumarins in a pH-dependent diastereoisomeric ratio. Subsequent decarboxylation gives optically active p-aryl nitroalkanes... 

Complementary to the use of zinc reagents for the introduction of (functionalized) alkyl groups is the rhodium-catalyzed conjugate addition of aryl- and alkenylboron reagents. This method rapidly became popular, also because arylboron reagents are air and moisture stable and a large variety of them is commercially available . 

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