Unactivated aliphatic electrophile

More recently, the use of unactivated aliphatic electrophiles in the transition-met-al-catalyzed cross-coupling reactions has attracted much attention [90,91]. In general, cross-coupling of a secondary alkyl halide is difficult because of a slow oxidative step and a fast /3-hydride elimination process. Nickel catalysts again have played a very important role in these reactions. 

Houk, Rovis, and their co-workers later extended the scope of the asymmetric intermolecular Stetter reaction of p-nitrostyrenes to unactivated aliphatic aldehydes, which have rarely been utilized in this reaction due to their relatively lower electrophilicity compared with aryl aldehydes. Comparing to known scaffolds, tert-leucine derived trans-fluorinated catalyst leads to improved reactivity and enantioselectivity in this transformation. Computational studies show that the optimized catalyst is the most stereoselective one because the Re-face attack is stabilized by favorable electrostatic interactions between the phenyl group and the fluorine on the catalyst backbone (Scheme 7.31). 

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