Addition reactions of Grignard reagents

Uncatalyzed addition reactions of Grignard reagents with nonconjugated alkenes and aUcynes are of limited use in synthesis. However, carbon-carbon double bonds substituted by a leaving group, such as an acetate, are susceptible to be displaced by organomagnesium compounds presumably by an addition-elimination pathway. A few examples have been reported (equation 64). 

Conjugate-addition Reactions of Grignard Reagents with a,)3-... 

The emphasis of this chapter will be on the mechanistic aspects of the ( normal ) addition reaction of Grignard reagents to the carbon-oxygen double bond, as is found for ketones. However, it will become clear that for reactions with other substrates, the general mechanistic aspects of these carbonyl addition reactions are also applicable. 

Since this chapter was prepared, several important papers on the subject have been published. Wang et al. used a modified amino acid as a chiral ligand to synthesize a chiral MOPM with ID channels (5.12 x 2.87 A ) [108]. The chiral MOPM catalyzes the addition reaction of Grignard reagent to a,P-unsaturated ketones with... 

Addition reactions of Grignard reagents to carbonyl compounds are also performed in microflow reactors. For example, the reaction of cyclohex-2-enone with isopropylmagnesium bromide leads to the formation of both 1,4-adduct A and 1,2-adduct B (Scheme 5.4). It is noteworthy that the microflow reactor serves a beneficial tool for optimization of the reactions conditions. By testing 14 different reaction conditions, the yield was increased from 49% to 78% and the ratio of the regioisomers was improved from 65 35 to 95 5 [12, 13]. 

C. Substituted Products - The introduction of an acetate group into the 7 xigl position has been accomplished by treating the 7-hydrazone with lead tetracetate. The stereochemistry of the addition reaction of Grignard reagents to 20-keto steroids was shown in the synthesis of 17a, 20a-dihydroxycholesterol. In such a manner C-27 side chain compounds, including one or more hydroxyl groups, could be synthesized. ... 

In the addition reaction of Grignard reagents to a carbon-carbon unsaturated bond, the yields and selectivities become higher by using transition metal catalysts, and so these reactions came to public notice. Metal compounds of Ti, Ni, Cu and Zr are used for the catalysts [55,56,99]. For example, the adduct is obtained in a high yield by a carbometalation reaction with zirconium catalysts as shown in eq. (4.36) [100]. On the other hand, cyclization proceeds in a high yield by using a diene as shown in eq. (4.37) [101]. 

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