Imines with organometallic reagents

Reaction of Nitriles with Organometallic Reagents Grignard reagents add to a nitrile to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone. 

Although the diastereoselective addition of nucleophiles to imines offers an attractive route to chiral amine derivatives, most chiral nonracemic imines suffer from low reactivity (electrophilicity), resulting in no reaction or competitive reduction with organometallic reagents. Other problems include enolization of aliphatic imines, poor... 

Enediamine 93 undergoes an easy C-alkylation with a,/ -unsaturated ketones under comparable conditions and no cyclocondensation products are observed36. Similar C-alkylations with other electrophilic olefins such as unsaturated lactones, propenonitrile, vinyl sulfoxide, sulfone and phenylphosphonium bromide have been achieved36. All the adducts 135 exist predominantly as the imine form (see Section II.A). Treatment with organometallic reagents transforms the C-alkylated products into... 

Oxidative sulfenylation of fluorinated amines. Anodic conditions convert the amines into sulfenylated imines, which can be used to react with organometallic reagents and enolates. 

There are some reports of syntheses and reactivities of inner salts of dithio-carboxylate, such as the bis(iV,Ar-substituted amino)carbenium dithiocarbox-ylates 87 [138-143]. The carbenium and dithiocarboxylate moieties are nearly perpendicular to each other in a quasi-plane [19,20,144]. Its sulfur atom reacts not only with methyl iodide to give carbenium iodide 88 [145], but also with organometallic reagents RM (M=Li,MgX) to give thiolates 89 [146],revealing a unique ability to serve both as a nucleophile and as an electrophile (Scheme 22). Furthermore, 87 is S-iminated by [iV-(p-tolylsulfonyl)imino]phenyliodinane to provide a novel inner salt 90 that formally possesses a thione-S-imide structure 90 as one of its canonical structures [143]. 

The addition of aryl groups to C=N bonds can be achieved using cooper-catalyzed asymmetric reactions with organometallic reagents. The addition of alkylzinc and related reactions is quite common in literature [47] whereas copper-catalyzed asymmetric arylation of imines is somewhat harder to find. We wish to report some successful examples of this type of catalysts. 

The enantioselective addition of organometallic reagents to, V-(trimethylsilyl)benzaldehyde imine (1) in the presence of enantiomerically pure modifiers has been investigated. The best result is obtained with butyllithium (the corresponding Grignard reagent affords both lower yield and selectivity, 1 fails to react with diethylzinc) and two equivalents of the enantiomerically pure diol 2 in diethyl ether. It should be noted that the choice of the solvent is crucial for the stereoselectivity of the reaction1 2 3 5 7 8 9. 

Nitrones have a more reactive C=N bond toward nucleophilic addition compared to imines. In spite of this fact, there have been only a limited number of studies on the nucleophilic addition reactions of nitrones, particularly organometallic reagents.352-355 During the last decade, research related to reactions of nitrones with zinc-containing reagents was essentially focused on (i) dialkylzinc-assisted alkynylations356-358 and vinylations359 of nitrones, (ii) catalytic asymmetric nucleophilic additions to the C=N bond,360-364 and (iii) nitrone allylations by allylzinc halides.365,366... 

Fluoral hydrate and hemiacetals are industrial products. They are stable liquids that are easy to handle, and they react as fluoral itself in many reactions. Thus, in the presence of Lewis acids, they react in Friedel-Crafts reactions. They also react very well with organometallics (indium and zinc derivatives) and with silyl enol ethers.Proline-catalyzed direct asymmetric aldol reaction of fluoral ethyl hemiac-etal with ketones produced jS-hydroxy-jS-trifluoromethylated ketones with good to excellent diastereo- (up to 96% de) and enantioselectivities. With imine reagents, the reaction proceeds without Lewis acid activation. The use of chiral imines affords the corresponding 8-hydroxy ketones with a 60-80% de (Figure 2.49). ° ... 

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