Organomagnesium compounds, addition

Addition of organomagnesium compounds to polarized multiple bonds O OMgX OH... 

The organozinc compound 2 is less reactive than an organomagnesium compound the addition to an ester carbonyl group is much slower than the addition to an aldehyde or ketone. Nevertheless the addition of 2 to the carbonyl group of unreacted a-halo ester 1 is the most frequently observed side-reaction ... 

Addition of organomagnesium compounds (Grignard reagents), generated from organohalides and magnesium metal, to electrophiles. 

The second route (Scheme 1) is a redistribution reaction, in fact the Schlenk equilibrium. This route may be used in the reverse direction for the preparation of pure diorganomagnesium compounds from organomagnesium halides. Addition of a ligand, usually dioxane, that forms an insoluble complex with magnesium dihalide, shifts the Schlenk equilibrium completely to the left side and allows isolation of pure diorganomagnesium compounds from the remaining solution. ... 

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). 

The reaction of aryl electrophiles with organomagnesium compounds is known as Kumada or Kumada-Tamao-Corriu reaction. The most common leaving groups in the electrophile are halogen atoms and, among them, chlorine is the most wanted due to the good availability and the low price of aryl or heteroaryl chlorides. Unfortunately, the oxidative addition of a metal center to an aryl chloride is a difficult reaction and many efforts have been made to overcome existing limitations. 

Similar acryloyl imidazolidinones have been used for the asymmetric 1,4-addition of organomagnesium compounds in the presence of a Lewis acid. The diastereoselectivity is variable and was found to be highly depending on the nature of all substrates. ... 

Organomagnesium compounds react with imines, prepared from 3-methoxy-2-naphth-aldehydes by a 1.4-addition mechanism. This reaction can be performed with high diastere-oselectivity. The method was applied for the synthesis of optically pure S-tetralones . Vinyhnagnesium bromide reacts as an acceptor with a ketone dimethyl hydrazone zincate 207, yielding a 1,1-bimetallic species, which can be reacted sequentially with two different electrophiles (equations 131 and 132) . The reaction proceeds via a metalla-aza-Claisen rearrangement, where the dimethylhydrazone anion behaves as an aza-allylic system . 

Functionalized organomagnesium compounds Synthesis and reactivity 569 2. Addition to oarbon-oxygen bonds... 

The enantioselective addition of organomagnesium compounds to ketones can be most conveniently performed by using a chiral auxiliary in the substrate molecule. Primary aUsyhnagnesium reagents react with aryl and heteroaryl ketones in the presence of magnesium TADDOLate at — 100°C, yielding products with up to 98% ee (equation 143). Chiral a-ketoacetals 214, prepared in two steps from a-substituted cinnamic aldehydes, add organomagnesium species with up to 98% diastereoselectivity (equation 144). 

Similarly, reaction of enamines such as 218 with benzotriazole affords a-aminoalkyl-benzotriazoles 219, which react smoothly with organomagnesium compounds, giving tertiary alkyl carbylamines 220 (equation 149) . The whole sequence can therefore be considered as the addition of Grignard reagents to imines. 

Chiral sulfinimines 236 are very useful intermediates for the preparation of enantiomer-ically pure primary amines 237 (equation 158) . This reaction has been applied to the synthesis of a-amino acids . For sulfinimines obtained from simple ketones, lithium reagents are preferable for the addition , while for cyclic ketones organomagnesium compounds gave the best results. Addition of alkyl and aryl Grignard compounds to sulfinimines, derived from 3- and 4-substituted cyclohexanones, proceeds with excellent diastereoselectivity, depending on the stereochemistry of the ring substituents rather than the sulfinyl group . 

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