Reaction with aldimines, ketimines

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)... 

Aldimines, Ketimines, and Related Compounds as Dipolarophiles Reactions of aldimines with nitrile oxides proceed readily to give 1,2,4-oxadiazolines independently of the nature of substituents both in dipole and dipolarophile molecules. 1,2,4-Oxadiazolines were prepared by the regiospe-cihc 1,3-dipolar cycloaddition of nitrile oxides with fluoro-substituted aldimines (295). Phosphorylnitrile oxides gave with azomethines, PhCH NR, phosphory-lated 1,2,4-oxadiazolines 129 (296). Expected 1,2,4-oxadiazolines were also obtained from azomethines, derived from 4-formylcoumarine (179) and 1,3-diphenylpyrazole-4-carbaldehyde (297). 

Various phenyl-substituted ketimines and aldimines react with metallocenes 1 and 2, in a manner that depends on the substituents present [41]. In all cases, elimination of the al-kyne is observed. Complex 2b reacts with PhN=CMePh to give the r 2-complex 64, which is stabilized by an additional pyridine ligand [41a], In the reactions of 1 or 2a with the ketimine HN=CPh2, hydrogen transfer generates complexes 65. Two molecules of the aldimine PhN=CHPh are coupled by 2a to give the cyclic diamido complex 66 [41b]. 

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

An interesting example is the hydroiminoacylation reaction, a good alternative to hydroacylation reactions, using aldimines as a synthetic equivalent to aldehydes (Scheme 4) [4]. The rhodium-catalyzed hydroiminoacylation of an olefin with aldimines produced a ketimine which could be further acid-hydrolyzed to give the ketone. The reaction proceeded via the formation of a stable iminoacylrhodi-um(III) hydride (this will be discussed in the mechanism section), production of which is facilitated by initial coordination of the rhodium complex to the pyridine moiety of the aldimine. This hydroiminoacylation procedure opened up the direct... 

The deprotonated aldimine is reprotonated at carbon-4 by reaction with a histamine residue to form the pyridoxamine phosphate ketimine. Hydrolysis of this complex yields the free oxoacid (oxaloacetate), leaving pyridoxamine phosphate at the catalytic site (Ivanov and Karpeisky, 1969). 

Various phenyl-substituted imines react with (26) in a maimer that depends on the substituents present but in all cases, elimination of the aUcyne is observed. The imine PhN=CMePh affords the -complex (35). On the contrary, with the ketimine HN=CPh2, complex (36) is generated by hydrogen transfer. Two molecules ofthe aldimine PhN=CHPh are coupled to give a five-membered diamido complex (37). An unusual reaction with 2-vinylpyridine takes place starting from (26) or (28). Monoazadienes (38) are formed, in which the aromaticity of the pyridine ring has been lost. 

Figure 24.9. Amino Acid Biosynthesis by Transamination. Within a transaminase, the internal aldimine is converted into pyridoxamine phosphate (PMP) by reaction with glutamate. PMP then reacts with an a-ketoacid to generate a ketimine. This intermediate is converted into a quinonoid intermediate, which in turn yields an external aldimine. The aldimine is cleaved to release the newly formed amino acid to complete the cycle.

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%... 

In the reactions of compounds of the halomethylalane type with compounds containing C=N double bonds (aldimines, ketimines, N heterocycles) both of these modes of reaction (A and B) have to be considered. So far, however, only the addition of CX to the C—N double bond has been detected with certainty (99). 

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. 

Chitosan is a multi-nucleophilic polymer due to the presence of the NH2 and OH functional groups. The initial sites where substitution occurs are the more nucleophilic amino groups. However, the experimental conditions and protection of the NH2 groups reduces the intermolecular hydrogen bonding and creates space for water molecules to fill in and solvate the hydrophilic groups of the polymer backbone (Sashiwa and Shigemasa 1999). A -alkylated derivatives can be obtained by the treatment of chitosan with aldehydes or ketones via formation of Schiff base intermediates, aldimines (from reactions with aldehydes), or ketimines (from reactions with ketones) followed by reduction of the imine with sodium borohydride. 

Lim and coworkers [102] examined the reaction of aldimines and ketimines with aikenes in the presence of [Rh(coe)2Cl]2/PCy3 (Scheme 19.71). Acidic hydrolysis of the produced imine provided the corresponding arylketone, ultimately rendering the overall transformation analogous to the Murai reaction. With this active catalytic system, the mono- and/or the dialkylated products were obtained in moderate to... 

Imines act as blocked amines because they hydrolyze to yield free amines, which react with an isocyanate. Ketimines also react directly with isocyanates to yield a variety of products, depending on the particular reactants and conditions. Aldimines react analogously with isocyanates to yield unsaturated substituted ureas. Since aldimines are more stable to hydrolysis than ketimines, the fraction undergoing direct reaction with isocyanate in the presence of water is greater than that with ketimines. Carboxylic acids react relatively slowly to form amides and CO2. Hindered carboxylic acid groups, such as in 2,2-dimethylolpropionic acid (3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid) [4767-03-7], react very slowly. 

Aldehydes and ketones react with ammonia and primary amines to form imines. Reaction with aldehydes yields aldimines, and ketimines arise in reactions with ketones (Figure 8.28). Imines derived from aliphatic carbonyl compounds are generally unstable and are transformed to more stable products, such as amines, diamines and others. Secondary amines react with aldehydes and ketones with the formation of enamines (Figure 8.29). Imines are similarly flavour-active compounds derived from furan-2-carbaldehyde. For example, the aromas of Ar-furfuryl(isobutylidene)amine, N-(furfuryl)isopentyhdeneamine (8-155) and N-(furfurylidene)isobutylamine (8-156) reportedly resemble chocolate. 

Alternative precursors for the synthesis of NHCs are thiourea derivatives of type 14. Kuhn and Kratz first reported a facile method for the synthesis of symmetrically substituted imidazol-2-thiones by the reaction of 3-hydroxy-2-butanone with suitable thiourea derivatives (Scheme 1.8a). Related saturated imidazolin-2-thiones 15 or benzimidazol-2-thiones 16 were obtained by reaction of aliphatic or aromatic 1,2-diamino compounds with thiophosgene (Scheme 1.8b). Unsymmetrically substituted imidazolin-2-thiones 17 were obtained by the reaction of lithium-A-lithiomethyldithiocarbamates with aldimines and ketimines, respectively (Scheme 1.8c). ... 

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