Ketones relative reactivity toward addition

Table 8.4. Relative Reactivity of Some Ketones toward Addition of Nucleophiles...

Giese and Kretzschmar7j found the rate of addition of hexenyl radicals to methyl acrylate increased 2-fold between aqueous tetrahydrofuran and aqueous ethanol, Salikhov and Fischer74 reported that the rate constant for /-butyl radical addition to acrylonitrile increased 3.6-fold between tetradecane and acetonitrile. Bednarek et al75 found that the relative reactivity of S vs MMA towards phenyl radicals was ca 20% greater in ketone solvents than it was in aromatic solvents. 

An interesting observation from organocuprate chemistry is that the initial step in 1,4-addition to enones may be electron transfer. Thus the relative reactivity of enones toward conjugate addition parallels their ease of reduction. One problem with any reaction between a ketone or aldehyde and a metal alkyl is deprotonation, when a hydrogens are present, to yield an enolate. Given the considerable basicity of metal alkyls, this side reaction should be anticipated. 

Relative reactivity of some ketones toward addition of nucleophiles... 

Holm and Crossland reported the product distribution (Scheme 5 and Table 1) in a reaction between f-BuMgCl and benzophenone. While the 1,2-addition affords the normal product, 1,6- and 1,4-additions should involve the fert-butyl radical for ortho- and para-additions, and the mechanism involves a single-electron transfer (SET). The product distribution indicates that the more sterically crowded benzophenones give more of the SET products. Ashby and Smith ° obtained relative rates for reactions of acetone and benzophenone (Table 2). Noteworthy is that those ketones have opposite reactivity orders toward R MgCl for the R variation. 

There is no doubt that aldehydes are more reactive than ketones toward nucleophiles. However, both carbonyl substrates are functionalized by activated nucleophiles e.g. RLi or RMgX (X=halogen), with poor chemoselectivity. For example, benzaldehyde is not a dominant species to be alkylated in the coexistence of acetophenone. Reetz and co-workers addressed these difficulties by systematic studies on ligand effects in carbonyl addition reactions of RMgL (L=relatively bulky ligand) [31]. Upon reacting a 1 1 mixture of PhCHO and PhCOMe with 1 equiv of RMgL in a competition experiment, the aldehyde reacted essentially exclusively to form adduct 2-H (Table 2-2, entries 2-A). 

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