Nitriles aldimines

However, the lone-pair electrons activate the a-hydrogens of aliphatic amines, and hydrogen is therefore removed by some reagents as easily from this site as from nitrogen. This leads to the formation of unsaturated compounds such as aldimines, nitriles, ketimines and enamines. The actual products depend on the amine structure (equations 68 to 71) and others may arise from subsequent hydrolysis, oxidation. 

From nitriles by treatment with anhydrous Stannous chloride dissolved in ether saturated with hydrogen chloride the resulting crystaUine aldimine stannichloride, [(RCH=NHj)2] SnCl, or (RCH=NH,HCl)2SnCl4, is hydrolysed by warm water, and the aldehyde is isolated by distillation with steam or by extraction with a solvent (Stephen reaction), for example, for R = CH3(CH2)4, i.e., n-amyl ... 

Interestingly, the diastereofacial selectivity can be reversed in the Strecker reaction of aldimines derived from galactosylamine 1 by simply changing the solvent. When the reaction of trimethylsilyl cyanide with the Schiff bases 2 catalyzed by zinc chloride, is carried out in chloroform instead of 2-propanol, there is a preferred formation of the (.S)-amino nitrile diastereomers63. 

Die Stephen-Reduktion von Nitrilen mit Tetrachlor-zinn(ll)-saure fiihrt zu Aldimin-Komplexen bzw. nach Hydrolyse zu Aldehyden (s. Bd. VII/1, S. 299ff. und Lit.1). Die Methode ist fur viele aliphatische Nitrile ungeeignet, da bei ihnen die primar entstehenden Nitriliumsalze ein zweites Molekiil Nitril addieren. In einzelnen Fallen bil-den sich bei der Stephen-Reduktion auch Amine (s. Bd. XI/1, S. 546). 

Some cycloaddition reactions of 4 are summarized in Scheme 1. This shows that silylene 4 undergoes reactions with nitriles [14], phosphaalkynes [15], silyl azides [16], diazabutadienes [17], 2,2 -bipyridyl and its derivatives [18, 19], a-ketoimines [19], and pyridine-2-aldimines [19]. 

Rapid monoalkylations are achieved in good yield compared with classical methods. Of particular interest is the synthesis of ot-amino acids by alkylation of aldimines with microwave activation. Subsequent acidic hydrolysis of the alkylated imine provides leucine, serine, or phenylalanine in preparatively useful yields within 1-5 min [50], Alkylation of phenylacetonitrile was performed by solid-liquid PTC in 1-3 min under microwave irradiation (Eq. 36 and Tab. 5.14). The nitriles obtained can subsequently be quickly hydrolyzed in a microwave oven to yield the corresponding amides or acids [56]. 

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). 

New catalyst design further highlights the utility of the scaffold and functional moieties of the Cinchona alkaloids. his-Cinchona alkaloid derivative 43 was developed by Corey [49] for enantioselective dihydroxylation of olefins with OsO. The catalyst was later employed in the Strecker hydrocyanation of iV-allyl aldimines. The mechanistic logic behind the catalyst for the Strecker reaction presents a chiral ammonium salt of the catalyst 43 (in the presence of a conjugate acid) that would stabilize the aldimine already activated via hydrogen-bonding to the protonated quinuclidine moiety. Nucleophilic attack by cyanide ion to the imine would give an a-amino nitrile product (Scheme 10). 

In 2006, the Rueping group showed that chiral phosphoric acid (R)-31 (10 mol%, R = 9-phenanthryl) with 9-phenanthryl substituents promoted the addition of HCN to iV-benzylated aldimines 83 (Scheme 31) [53]. a-Amino nitriles 84 were obtained in good yields (53-97%) along with high enantioselectivities (85-99% ee) and could be transformed into the corresponding a-amino acids. 

List and co-workers reported the 47-catalyzed (lmol% loading) asymmetric acetylcyanation of N-benzyl-protected aliphatic and aromatic aldimines by using commercially available liquid acetyl cyanide as the cyanide source instead of HCN [161]. Under optimized reaction parameters (toluene, -40 °C) the procedure resulted in the desired N-protected a-amino nitriles 1-5 in yields ranging from 62... 

STEPHEN ALDEHYDE SYNTHESIS. Preparation of aldehydes from nitriles by reduction with stannous chloride in ether saturated with hydrochloric acid. The intermediate aldimine salts have to be hydrolyzed. The best results are obtained in the aromatic series. 

The reduction of the nitrile proceeds stepwise with formation of a primary aldi.nine which then is hydrogenated to the primary amine (pentyl ami ne). Part of the aldimine condenses with primary amine already formed to produce the unstable aminal. This intermediate looses ammonia to yield a secondary aldimine (dipentylimine) which ultimately leads to secondary amine (dipentyl amine). The reaction of the same primary imine with the secondary amine gives rise to the tertiary amine (tripentylamine), after hydrogenation. 

With enamino nitrile 9 intramolecular hydrogen bonding cannot take place so a rapid isomerization occurs between 13a and 13b giving rise to the trans AMCPA as the major isomer after hydrogenation. Isomerization to 13b is reinforced also by the slower rate of hydrogenation of a nitrile group than an aldimine one. 

Shibasaki and co-workers applied (BINOL)Al(III)-derived catalyst 5a, previously developed for the cyanation of aldehydes [28], to the asymmetric Strecker reaction. This catalyst proved to be highly enantioselective for both aromatic and a,p-unsaturated acyclic aldimines (>86% ee for most substrates) (Scheme 8) [63-65]. Aliphatic aldimines underwent cyanide addition with lower levels of enantioselectivity (70-80% ee). A significant distinction of 5 relative to other catalysts is, undoubtedly, its successful application to the hydrocyanation of quinolines and isoquinolines, followed by in situ protection of the sensitive cx-amino nitrile formed (this variant of the Strecker reaction is also known as the Reissert reaction [66]). Thus, Shibasaki has shown that high enantioselectivities (>80% ee for most substrates) and good yields are generally obtainable in the Reissert reaction catalyzed by 5b [67,68]. When applied to 1-substituted... 

The reduction of a nitrile is achieved with anhydrous tin(n) chloride dissolved in ether or ethyl acetate saturated with dry hydrogen chloride (the Stephen reaction). The resulting aldimine hydrochloride (probably in the form of a complex with tin(iv) chloride) is then hydrolysed with warm water. 

The Feng group showed that organic molecules without an imine bond also seem to be able to catalyze the cyanation of imines [14]. In the presence of (stoichiometric) amount of a chiral N-oxide, 19, addition of trimethylsilylcyanide to several types of aldimine gave the desired a-amino nitriles with enantioselectivity up to 73% ee [14]. For example, (S)-4a is obtained in 95% yield and with 58% ee (Scheme 5.10). In addition to medium enantioselectivity, a drawback of this method is the need for stoichiometric amounts of the chiral N-oxide. The use of trimethylsilylcyanide is also less recommendable than HCN from both atom-economical and industrial considerations. 

Nitrile-stabilized anions, generated for example by lithiation of benzyl cyanide and propionitrile, have been added diastereoselectively to aromatic aldimines.50 Acid workup gives /5-cyano amines. Alternatively, addition of RX gives /3-R-substituted-/3-cyanoamines. The factors determining des in both reaction versions have been investigated. 

It appears probable that the aldimine II, initially formed by hydrogenation of the nitrile group, is itself in the stabilized, cyclic-hemiacetal form as a 1,2-diamino-l, 2-dideoxy derivative (III), the 1-amino group of which is subsequently hydrolyzed to yield the cyclic 2-amino-2-deoxy sugar (IV) directly.10 10a... 

The Strecker reaction is defined as the addition of HCN to the condensation product of a carbonyl and amine component to give a-amino nitriles. Lipton and coworkers reported the first highly effective catalytic asymmetric Strecker reaction, using synthetic peptide 43, a modification of Inoue s catalyst (38), which was determined to be inactive for the Strecker reactions of aldimines (see Scheme 6.5) [62], Catalyst 43 provided chiral a-amino nitrile products for a number of N-benzhydryl imines (42) derived from substituted aromatic (71-97% yield 64->99% ee) and aliphatic (80-81% yield <10-17% ee) aldehydes, presumably through a similar mode of activation to that for hydrocyanations of aldehydes (Table 6.14). Electron-deficient aromatic imines were not suitable substrates for this catalyst, giving products in low optical purities (<10-32% ee). The a-amino nitrile product of benzaldehyde was converted to the corresponding a-amino acid in high yield (92%) and ee (>99%) via a one-step acid hydrolysis. 

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