Grignard reactions transition-state structures

The diastereoselectivity of the reaction may be rationalized by assuming a chelation model, which has been developed in the addition of Grignard reagents to enantiomerically pure a-keto acetals7,8. Cerium metal is fixed by chelation between the N-atom, the methoxy O-atom and one of the acetal O-atoms leading to a rigid structure in the transition state of the reaction (see below). Hence, nucleophilic attack from the Si-face of the C-N double bond is favored4. 

The application of the concept of reactivity in such structure reactivity relationships has not yet been firmly established in Grignard chemistry. Only rather recently have successful and reliable kinetic measurements been published, and their application in attempts to elucidate mechanisms of reactions of organomagnesium compounds has just begun (see Chapter 11). Detailed mechanistic studies, such as structures of transition states, entropies of reactions, and so on, are still scarce furthermore, such information is rather haphazard. 

Another notable difference between the Zr-catalyzed ethylmagnesations of allylic ethers and alcohols is the effect of solvent Lewis basicity on reaction selectivity. Thus, as iUustrated in Scheme 3.79, whereas reactions with allylic ethers are entirely insensitive to variations in solvent structure, those of allylic alcohols are strongly influenced. These observations led Hoveyda and coworkers to conclude that for allylic alcohols (allyhc alkoxides after rapid deprotonation by the Grignard reagent) there is chelation between the Lewis basic heteroatom and a metal center (Zr or Mg) this association, which gives rise to transition state organization and high diastereocon-trol, is altered in the presence of Lewis basic THF, with diminution in selectivity. 

Benzyl halides and allyl (propargyl) halides are structurally similar but have drastically different chemical reactivities in the aqueous Barbier-Grignard-type reactions. Although tribenzyl and dibenzyltin derivatives have been prepared in aqueous conditions since the 1960s, they do not add onto carbonyls, most likely because it is not possible to form a six-membered cyclic transition state with the carbonyl group in a two-componenf fashion. Still, zinc-mediated benzylation of carbonyl compounds in aqueous media was reported by Bieber et al. recently. The benzylation of 4-nitrobenzaldehyde could be controlled chemoselectively by using various phase transfer catalysts and metal reductants in water (Eq. 4.41). 2... 

Organic bromides fall between iodides and chlorides, the rate-controlling step containing contributions from mass transfer and chemical reaction. Hammett p constants for bromobenzene support any of the last three transition states. In the last of the four papers " rate-structure profiles for the formation of Grignard reagents are shown to correlate, with coefficients between 0.73 and 0.99, with other processes involving the electrochemical and chemical reduction of alkyl halides. 

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