Ketones imine derivatives

A range of electron-withdrawing groups on the nitrogen - N-P(0)Ph2, N-tosyl, and N-SES, for example - were tolerated. Imines derived from aromatic, heteroaromatic, unsaturated, and even aliphatic aldehydes and ketones were employed... 

One of the potentially most useful aspects of the imine anions is that they can be prepared from enantiomerically pure amines. When imines derived from chiral amines are alkylated, the new carbon-carbon bond is formed with a bias for one of the two possible stereochemical configurations. Hydrolysis of the imine then leads to enantiomerically enriched ketone. Table 1.4 lists some examples that have been reported.118... 

Amines can react with various carbonyl compounds and their derivatives in aqueous media to give the corresponding imine derivatives. These reactions have been discussed in related chapters. The synthetically most useful reaction of this type is the formation of imines and imine derivatives from the condensation of amines with aldehydes and ketones. Water is an excellent solvent for such condensation reactions. For example, water was found to be an ideal solvent for a high-yield, fast preparation of easily hydrolyzable 2-pyrrolecarbaldimines.23 In the presence of Cu2+, the reaction afforded the corresponding Cu(II) chelates (Eq. 11.19). 

I 75 Homogeneous Hydrogenation of Aldehydes, Ketones, Imines, and Carboxylic Acid Derivatives... 

Kinetic resolution results of ketone and imine derivatives are indicated in Table 21.19. In the kinetic resolution of cyclic ketones or keto esters, ruthenium atrop-isomeric diphosphine catalysts 25 induced high enantiomer-discriminating ability, and high enantiopurity is realized at near 50% conversion [116, 117]. In the case of a bicyclic keto ester, the presence of hydrogen chloride in methanol served to raise the enantiomer-discriminating ability of the Ru-binap catalyst (entry 1) [116]. 

An extension of the strategy described for the reaction with aldehydes (Section 5.4.2) to imine derivatives might be expected to yield a-amino ketone compounds (Scheme 5.14), which are the constituents of a variety of biologically important molecules. 

Although the reactivity of acylzirconocene chlorides towards imine derivatives under Yb(OTf)3/TMSOTf (20 mol%, l l)-catalyzed conditions is not necessarily very high, the direct access to a-amino ketone derivatives indicates the usefulness of acylzirconocene chlorides as unmasked acyl anion donors. 

Imines derived from ketones with an a-methylene group can react via their enamine tautomers, and mixtures of triazoles are also isolated from these systems. The triazoline adducts of the enamine tautomers are aromatized by treating with acid, and in these conditions the triazoline appears to undergo a Dimroth rearrangement before elimination of the amine, because two triazoles are obtained, one of which has... 

Since imines derived from alkyl-alkyl ketones are relatively unstable, reductive amination may be more practical compared to imine reduction. Compared to the reductive amination, which employs three equivalents of the ketone substrate, the in situ imine generation/one-pot reduction protocol has the significant advantage that it does not require an excess of the carbonyl compound. 

Furthermore, Rueping and coworkers applied their reaction conditions to the cyanation of ketimines [54]. The use of A-benzylated imines derived from aryl-methyl ketones generally gave comparable yields, but lower enantioselectivities. However, this method furnished Strecker products bearing a quaternary stereogenic center, which are valuable intermediates for the preparation of optically active a,a-disubstituted a-amino acids. 

Gaul and Seebach showed that lithiated methylthiomethyl-substituted chiral oxazolidi-nones react with aldehydes, ketones, imines and chalcones (Scheme 41). In this case, the oxazolidinone is derived from diphenylvalinol. The products, with two new asymmetric centers, are formed in good yield and excellent diastereoselectivity.A detailed mechanistic study of this and related systems, using computational methods, IR and NMR... 

In contrast to earlier known imines, those imines derived from a-(methoxymethyl)benzene-ethanamine, which allow formation of a rigid chelate by additional coordination of the lithium with the methoxy group, enabled the preparation of a-alkylated cyclic ketones in very high enantiomeric excesses (90-99% ee)7,8. However, alkylations of imines derived from medium ring ketones were accomplished in 30-82% ee9. The alkylation of acyclic ketones was performed with enantiomeric excesses of more than 75 % and, in the case of the imine derived from 4-heptanone, proceeded with complete asymmetric induction10. 

Chronologically, alkylation reactions of ketones via their imine derivatives were the first examined in asymmetric C C bond formation1. 

In contrast to the chemical properties of enolates, azaenolates of imines exhibit a marked thermodynamic preference for the syn configuration at the C-N partial double bond (syn effect)2 due to the repulsion between the lone pair density at nitrogen and the 7t-electron density at the carbon. Thus, lithiation of imines derived from ketones occurs with strong regioselectiv-ity at the least substituted carbon, followed by a regioselective reaction with electrophiles exclusively at the carbon of the ambident azaalkyl moiety. 

Imines derived from macrocyclic ketones (C10 to C 15 ) and (- )-(S)-a-(methoxymcthyl)benzene-ethanamine are successfully deprotonated using LDA ( —25 JC. THF. 1 h)9. In contrast to azaenolates of C0- to C8-membered cyclic ketones, which show only E geometry, Z-isomers are observed with macrocyclic imines. As evident from H-NMR data, azaenolates of cyclodecanone imines generated under these conditions are a mixture of E- and Z-isomers (33 66), whereas azaenolates of cyclododecanone and cyclopenladecanone imines arc formed as the pure. E-isomers (see Table 3). Upon heating the solutions of metalated imines to reflux for 1 hour, complete isomerization to the thermodynamically more stable Z-isomers occurs. 

Umsetzung des intermediaren Dilithio-Derivates mit Benzaldehyd-phcnyliminen oder einem Keton-imin (z.B. 1-Phenyl-l-phenylimino-propan) fiihrt zur Bildung von 1,3-Dianili no- alkane n1 ... 

The most general method for synthesizing amines involves the reduction of oximes and imine derivatives obtained from aldehydes or ketones (see Sections 5.5.2 and 4.3.11). By catalytic hydrogenation or by LiAltLj reduction, while 1° amines are prepared from oxime or unsubstituted imine, 2° amines are obtained from substituted imine. Unsubstituted imines are relatively unstable, and are reduced in situ. 

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