Aldimines and Ketimines

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  

The imines (Schiff s bases) have found most general application. Their preparation as well as the conversion of their derivatization products into aldehydes or ketones can be carried out under mild conditions and with satisfactory yields using extremely simple auxiliary reagents. 

The chemistry of the metallated nitrogen derivatives of aldehydes and ketones has been reviewed by Mukaiyama [4] and Whitesell-Whitesell [5]. 

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Iminium salts can be made in a number of ways such as protonation of enamines (7), alkylation of aldimines and ketimines (5,9), cleavage of a covalent bond in a... 

The alkylation of aldimines and ketimines as a method for obtaining iminium salts is now useful only for the preparation of iminium salts not accessible by any of the newer methods. The preparation of and 8 illustrates the conversion of ketimines to iminium salts (9,21). 

The Schiff reaction between chitosan and aldehydes or ketones yields the corresponding aldimines and ketimines, which are converted to N-alkyl derivatives upon hydrogenation with borohydride. Chitosan acetate salt can be converted into chitin upon heating [130]. The following are important examples of modified chitosans that currently have niche markets or prominent places in advanced research. 

Recent efforts in the development of efficient routes to highly substituted yS-ami-no acids based on asymmetric Mannich reactions with enantiopure sulfmyl imine are worthy of mention. Following the pioneering work of Davis on p-tolu-enesulfmyl imines [116], Ellman and coworkers have recently developed a new and efficient approach to enantiomerically pure N-tert-butanesulfmyl imines and have reported their use as versatile intermediates for the asymmetric synthesis of amines [91]. Addition of titanium enolates to tert-butane sulfmyl aldimines and ketimines 31 proceeds in high yields and diastereoselectivities, thus providing general access to yS -amino acids 32 (Scheme 2.5)... 

The addition of terminal acetylenes to imines is an important reaction because of the importance of these products as building blocks. Conventionally, the addition reaction shown in Scheme 5.2 is performed with stoichiometric amounts of butyllithium in a step that is, separate from the subsequent nucleophilic addition reaction (see (b)). Carreira has recently developed a procedure that utilizes an iridium catalyst to effect the addition reaction to a wide range of aldimines and ketimines (see (a)). ... 

Other substrates with C=N double bonds frequently used in organic synthesis, such as aldimines and ketimines, will be considered in Section 10.7.5. 

Reaction of Various Aldimine and Ketimine Magnesium Bromide Salts with Alkylating Agents in Tetrahydrofuran... 

Kondo, Aoyama and co-workers expanded tMs chemistry to include aldimines and ketimines in good yields under mild reaction conditions (Scheme 49) [164, 165], Maruoka and co-workers also report cyanosilylation of tosyl and benzyl imines [166],... 

Imidazoles/benzimidazoles and chiral carbinamines are of particular importance [73, 74], Recently, Leighton et al. developed a method for enantioselec-tive imidazole directed allylation of aldimines and ketimines [75] with an analogue of 31. 

On the basis of the observed stereoinduction trend, the addition of HCN took place over the diaminocyclohexane portion of the catalyst away from the amino acid and amide unit. The last hypothesis led to the prediction that a more sterically demanding amino acid or amide unit (Figure 6.14) could additionally favor the cyanide attack compared to the less bulky diaminocyclohexane unit and thus making the Schiff base catalyst more enantioselective in Strecker reactions of aldimines and ketimines. To evaluate this perspechve, the authors performed a model-(mechanism-) driven systematic structure optimizations by stepwise modification of the amide, the amino acid, and the (thio)urea unit of catalyst 42 and examined these derivatives of 42 (lmol% loading ) in the model Strecker reaction (toluene ... 

Early work on H chemical shifts of oximes, hydrazones, aldimines and ketimines has been collected286. It was shown that an oc-proton is always deshielded (increased 6 value) when it is cis relative to the group X at the nitrogen 1, compared to the trans orientation 2, with chemical shift differences varying between 0.2 and 1.35 ppm. The same is valid for R1 = H, where Ad is 0.3 to 1.0 ppm. 

Addition of Aromatic Azides to Enamines, Aldimines, and Ketimines... 

Established methods for making 1,2,6-thiadiazines that have no 1,1-dioxide group include reactions of (i) sulfur diimides with malonyl chlorides and 1,3-diaminopropanes, (ii) sulfur dichloride with 1,3-diaminopropanes, and (iii) thionyl chloride with N.N-l,5-dinucleophiles such as 1,3-diaminopropanes or /3-amino a,/3-unsaturated aldimines and ketimines to give 5-oxides (79MI1 84MI1). 

Epoxidation of both aldimines and ketimines is possible. Most oxaziridines formed are stable compounds, especially aldimines containing aromatic substituents, and 2-sulfonyl-and 2-sulfamyl oxaziridines5. Generally, /V-sulfonyloxaziridines are isolated as stable crystalline solids. Certain compounds are widely used in synthetic organic chemistry as oxygen-transfer reagents (15-17). 

Phenols have been employed as directing groups in the enantioselective allylation of aldimines and ketimines using allylchlorosilane reagents.45... 

Aldehydes and ketones react with primary amines to give a reaction product (a carbinolamine) that dehydrates to yield aldimines and ketimines (Schiff bases). 

A very efficient method for hydrocyanation of aldimines and ketimines has been developed by the Jacobsen group. Chiral urea or thiourea derivatives containing an imine bond of type 9 and 10 were used as organocatalysts [7-13]. The core... 

Enantiomerically pure /3-nitroamines of enolizable aldimines and ketimines have been accessed via a diastereoselective aza-Henry reaction of A-sulfinylimines and nitromethane.37 The reaction is catalysed by sodium hydroxide, but also by tetrabuty-lammonium fluoride, the latter species giving an inversion of stereochemistry. An CT -+N contact ion pair is proposed in the ammonium-catalysed route. 

The reductive-trimethylsilylation of imines by means of granulated lithium in THF at 0-5 °C is a good method to synthesize ASMA and RSMA. This process was applied to aldimines and ketimines, lower yields being obtained in the latter case.190... 

Scheme 7.49. Scope of Ag-catalyzed di-tert-butylsilylene transfer to aldimines and ketimines.

Having successfully accelerated the reversible isomerization between the aldimine and ketimine Schiff bases, Murakami et al. then studied how to obtain turnovers in the full transamination reaction between one amino acid and one keto acid [25]. They found that the bilayer vesicle system constituted with 33, 36, and Cu(n) ions showed some turnovers for the transamination between L-phenylalanine and pyruvic add. However, such turnover behavior was not observed in a vesicular system composed of 32, 36, and Cu(n) ions, and an aqueous system involving N-methylpyridoxal and Cu(n) ions without amphiphiles. Therefore, both the hydrophobic effect and the imidazole catalysis effect were proposed as important for the turnover behavior. 

The initial step in the reduction in acid solution of azines, hydra-zones, and substituted hydrazones has been suggested to be a hydrogenolysis of the nitrogen-nitrogen bond.91 The aldimine and ketimine thus formed are usually, but not always, reduced further at the potential necessary for the reductive cleavage this depends on the nature of the substituents. The general reduction scheme for a hydrazone is shown in Scheme 8. 

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