Imines with aldehydes

In contrast to the amt-selective reaction of lithiated imines with aldehydes, titanated imines, prepared by transmetalation of the corresponding lithium azaenolates, give predominantly. sFH-adducts2. 

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

Secondary amines cannot form imines with aldehydes and ketones but... 

It was reported that proline catalyzed the direct catalytic asymmetric Mannich reactions of hydroxyacetone, aldehydes, and aniline derivatives [(Eq. (10)] [40-44]. Not only aromatic aldehydes but also aliphatic aldehydes worked well in this reaction, and good to excellent enantioselectivity and moderate to excellent yields were observed. Mannich reactions of glyoxylate imines with aldehydes or ketones were also successfully performed [45,46]. 

P-Hydroxyalkanitriles containing a chiral quaternary a-carhon atom are available from condensation of A-silyl ketene imines with aldehydes. The process is mediated by SiCLt, and chiral information comes from 69. ... 

Secondary amines cannot form imines with aldehydes and ketones, but are in equilibrium with the corresponding Af,Af-dialkyliminium ions (Section 17-9), which are reduced by addition of H from cyanoborohydride. 

Reaction of primary amines with aldehydes and ketones (Section 17.10) Imines are formed by nucleophilic addition of a primary amine to the carbonyl group of an aldehyde or a ketone. The key step is formation of a carbinolamine intermediate, which then dehydrates to the imine. 

Imine formation is reversible. Show all the steps involved in the acid-catalyzed reaction of an imine with water (hydrolysis) to yield an aldehyde or ketone plus primary amine. 

Step 1 of Figure 29.14 Transimination The first step in transamination is trans-imination—the reaction of the PLP—enzyme imine with an a-amino acid to give a PLP—amino acid imine plus expelled enzyme as the leaving group. The reaction occurs by nucleophilic addition of the amino acid -NH2 group to the C=N bond of the PLP imine, much as an amine adds to the C=0 bond of a ketone or aldehyde in a nucleophilic addition reaction (Section 19.8). The pro-tonated diamine intermediate undergoes a proton transfer and expels the lysine amino group in the enzyme to complete the step. 

The synthesis of the E-ring intermediate 20 commences with the methyl ester of enantiomerically pure L-serine hydrochloride (22) (see Scheme 9). The primary amino group of 22 can be alkylated in a straightforward manner by treatment with acetaldehyde, followed by reduction of the intermediate imine with sodium borohydride (see 22 —> 51). The primary hydroxyl and secondary amino groups in 51 are affixed to adjacent carbon atoms. By virtue of this close spatial relationship, it seemed reasonable to expect that the simultaneous protection of these two functions in the form of an oxazolidi-none ring could be achieved. Indeed, treatment of 51 with l,l -car-bonyldiimidazole in refluxing acetonitrile, followed by partial reduction of the methoxycarbonyl function with one equivalent of Dibal-H provides oxazolidinone aldehyde 52. 

The condensation of 2,5-diunsubstituted pyrroles with formic acid20 is a viable method to produce porphyrins. However, the most common procedure21 22 involves the heating of the corresponding pyrroles 1 with aldehydes and aldehyde derivatives like imines or a Mannich reagent in the presence of acid. The reaction is initiated by electrophilic attack of the aldehyde (or aldehyde derivative) to the pyrrole 1. The formed (hydroxyalkyl)pyrrole 3 then undergoes electrophilic substitution with another pyrrole to form a dipyrrylmethane 4. Repeated addition of aldehyde and pyrrole finally forms a tetrameric (hydroxyalkyl)bilane 5. 

A novel guanidinium ylide-mediated procedure has recently been reported by Ishi-kawa [62]. Though not an imine transformation, it does employ an imine precursor in the fonn of an aldehyde. Guanidinium ylides react with aldehydes to form aziridines (Scheme 1.35). The mechanism for the formation of the aziridine is believed to involve [3+2] cycloaddition between the guanidinium ylide 112 and the aldehyde, followed by stereospecific extrusion of the urea with concomitant aziridine formation. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Primary and secondary halides do not perform well, mostly because N-alkylation becomes important, particularly with enamines derived from aldehydes. An alternative method, which gives good yields of alkylation with primary and secondary halides, is alkylation of enamine salts, which are prepared by treating an imine with ethylmagnesium bromide in THF ... 

The addition of ammonia to aldehydes or ketones does not generally give useful products. According to the pattern followed by analogous nucleophiles, the initial products would be expected to be hemiaminals, but these compounds are generally unstable. Most imines with a hydrogen on the nitrogen spontaneously poly-... 

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). 

As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

Similar aza-Diels-Alder reactions of Danishefsky s diene with imines or aldehydes and amines in water took place smoothly under neutral conditions in the presence of a catalytic amount of an alkaline salt such as sodium triflate or sodium tetraphenylborate to afford dihydro-4-pyridones in high yields (Eq. 12.49).117 Antibodies have also been found to catalyze hetero-Diels-Alder reactions.118... 

The N-terminal methionine residue of protein can also be employed for selective PEGylation using aldehyde-terminated PEG via a reductive amination reaction, because the N-terminal primary amine has a lower pAa of 7.8 than other amines such as lysines, whose pZa is 10.1 [7]. After reaction with aldehyde-terminated PEG at low pH, the resultant imine is reduced with sodium cyanoborohydrate to provide PEGylated protein (Fig. 4) [8, 9]. This technique was used for the production of Neulasta, which was approved for use by the FDA in 2002 [10]. 

Fig. 4 PEGylation at the N-terminal methionine residue. The difference in pKa. between the N-terminal amine and other amines in the protein enables site-specific PEGylation. After reaction with aldehyde-terminated PEG at low pH, reduction of the resultant imine produces PEGylated protein...

The Friedlander reaction is the acid- or base-catalyzed condensation of an ortho-acylaniline with an enolizable aldehyde or ketone. Henichart and coworkers have described microwave-assisted Friedlander reactions for the synthesis of indoli-zino[l,2-b]quinolincs, which constitute the heterocyclic core of camptothecin-type antitumor agents (Scheme 6.238) [421], The process involved the condensation of ortho-aminobenzaldehydcs (or imines) with tetrahydroindolizinediones to form the quinoline structures. Employing 1.25 equivalents of the aldehyde or imine component in acetic acid as solvent provided the desired target compounds in 57-91% yield within 15 min. These transformations were carried out under open-vessel conditions at the reflux temperature of the acetic acid solvent. 

It has been shown by Varma et al. [61] that reaction of primary and secondary amines with aldehydes and ketones is substantially accelerated by microwaves under solvent-free conditions in the presence of montmorillonite K10 clay, affording high yields of imines and enamines (Eq. 10). 

MW-expedited dehydration reactions using montmorillonite K 10 clay [70] (Schs. 6.20 and 6.21) or Envirocat reagent, EPZG [71] (Schs. 6.20 and 6.21) have been demonstrated in a facile preparation of imines and enamines via the reactions of primary and secondary amines with aldehydes and ketones, respectively. The generation of polar transition state intermediates in such reactions and their enhanced... 

The tetrachloroferrate or tetralluoroborate salts of alkylated alkyl- or aryl-nitriles (nitrilium ions) are reduced to imines with triethylsilane. Subsequent hydrolysis of the intermediate imines leads to aldehydes in good yields, thus providing an excellent overall route to aldehydes from nitriles (Eq. 338).28,562... 

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