Reaction with metalated aldimines

Reaction of metalated aldimines with aldehydes or epoxides... 

Reaction of alkyl halides with metalated aldimines... 

Table 1 Directed Aldol Reactions of Metallated Aldimines with Carbonyl Compounds (Scheme 3)...

Whitesell and Whitesell" have tabulated some of the many types of electrophilic reagents that C-al-kylate metallated imines. These are potent nucleophiles and undergo substitution reactions even with weakly electrophilic species such as epoxides and oxetanes. Lithiated ketimines and aldimines have been frequently used in reactions with alkylating agents containing latent 2-keto (or aldehydo) groupsor 3-keto (or aldehydo) groups. ... 

The pioneering work of Stork and coworkers and Wittig and coworkers on the metallation of ketimines, and their subsequent reaction with a variety of electrophiles, has proven extremely useful for controlled aldol condensation and also for regioselective functionalization of ketones Recently, reactions of chiral lithiated ketimines and aldimines have been established as an important method of asymmetric synthesis, producing chiral ketones in optical yields as high as 95%... 

The reaction of allyl organometallics (8) with achiral aldimines (9) is the simplest combination of reactants, stereochemically, and affords (except in the case of formaldehyde imines) homoallylamines (10) containing one stereocenter (equation 2). These reactions, which typify the general scope of allyl organo-metallic-imine reactions are surveyed in Table 2. Reactions of allyl-borane, -titanium and -aluminum reagents are not shown in Table 2, only because they have been reported in reactions with chiral imines and are discussed in Sections 4.3.2.1.2 and 4.3.2.2. 

Directed functionalizations at the a-carbon atom of aldehydes and ketones have been carried out via reactions of their nitrogen derivatives, including aldimines, ketimines, hydrazines, and oximines. The general procedure involves metallation of the nitrogen derivative, subsequent reaction with an electrophile and final conversion of the obtained derivative into the derivative of the starting aldehyde or ketone. The reaction sequence is depicted in the following general scheme ... 

In this chapter, some procedures with simple aldimines and ketimines are described. They show representative conditions for the metallation of these nitrogen derivatives, their subsequent reactions with a number of electrophiles and the final hydrolytic cleavage of the C=N bond with formation of derivatives of the starting aldehydes or ketones. 

Their formation can be rationalized in several ways. It may involve insertion of the isocyanide into the M—Et bond of an intermediate monoethyl complex, but it can also be explained by substitution of one of the chloro ligands in the starting material by the metalated aldimine, which results from the reaction of f-BuNC with EtMgCl. NMR data suggest a dynamic coordination behavior for the tethered ether ligand and also for the (imino)propionyl group, whose coordination mode may be either or... 

The effect of the metals used was then examined (Table 5.4). When the group 4 metals, titanium, zirconium, and hafnium, were screened it was found that a chiral hafnium catalyst gave high yields and enantioselectivity in the model reaction of aldimine lb with 7a, while lower yields and enantiomeric excesses were obtained using a chiral titanium catalyst [17]. 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

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