Hydrogenation aldimines

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 ... 

Into a 500 ml. three-necked flask, provided with a mechanical stirrer, a gas inlet tube and a reflux condenser, place 57 g. of anhydrous stannous chloride (Section 11,50,11) and 200 ml. of anhydrous ether. Pass in dry hydrogen chloride gas (Section 11,48,1) until the mixture is saturated and separates into two layers the lower viscous layer consists of stannous chloride dissolved in ethereal hydrogen chloride. Set the stirrer in motion and add 19 5 g. of n-amyl cyanide (Sections III,112 and III,113) through the separatory funnel. Separation of the crystalline aldimine hydrochloride commences after a few minutes continue the stirring for 15 minutes. Filter oflF the crystalline solid, suspend it in about 50 ml. of water and heat under reflux until it is completely hydrolysed. Allow to cool and extract with ether dry the ethereal extract with anhydrous magnesium or calcium sulphate and remove the ether slowly (Fig. II, 13, 4, but with the distilling flask replaced by a Claisen flask with fractionating side arm). Finally, distil the residue and collect the n-hexaldehyde at 127-129°. The yield is 19 g. 

If, however, hydrogen is present in the a-position of the iV-alkyl substituent, 2-alkyl-oxaziridines are easily decomposed by alkali. Base attack on this H atom effects 1,2-elimination at the C—N bond. From (86) and aldimine (87) forms, and a mixture of ammonia and two carbonyl compounds is finally obtained, one of them containing the carbon atom of the original oxaziridine ring, the other originating from the IV-alkyl group (57JA5739). 

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. 

Isocyanides that do not contain an a hydrogen react with alkyllithium compounds, as well as with Grignard reagents, to give lithium (or magnesium) aldimines. These metalated aldimines are versatile nucleophiles and react with various substrates as follows ... 

Wada, M., Sakurai, Y., Akiba, K.-y. (1984) Addition of Alkynyl Anions to Aldimines Containing A-Hydrogens A Novel Synthesis offi-Aminoacetylenes. Tetrahedron Letters, 25, 1083-1084. 

The inlet tube is replaced by a dropping funnel, and a solution of 30.6 g. (0.2 mole) of jS-naphthonitrile, m.p. 60-62° (Note 2), in 200 cc. of dry ether is added rapidly. Hydrogen chloride is again passed into the mixture until it is saturated, and the mixture is then stirred rapidly for one hour and allowed to stand overnight while the yellow aldimine-stannichloride separates completely. 

Lukszo, J., Kowalik, J., and Mastalerz, R, Advantages of using di(p-methyl-benzyl) hydrogen phosphite in the synthesis of aminophosphonates from aldimines, Chem. Lett., 1103, 1978. 

Ketimines were hydrogenated faster than aldimines, and electron-donating groups accelerated the rate of hydrogenation. The OH and RuH bonds are regenerated by hydrogen transfer to the unsaturated 16-electron Ru complex from isopropanol, generating acetone (Scheme 7.13). 

The transfer hydrogenation of aldimines has not been reported. In our own studies we have tested the simple Schiff base adduct between benzylamine and benzaldehyde and shown this to be reduced in straightforward manner. 

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]. 

A new cinchona alkaloid-derived catalyst has been developed for the enantioselective Strecker reaction of aryl aldimines via hydrogen-bonding activation. For reference, see Huang, J. Corey, E. J. Org. Lett. 2004, 6, 5027-5029. 

Methane Hydrogen phosphate Ammonium Alkene Carbonyl Aldimine... 

Aldimines derived from aromatic aldehydes suffered hydrogenolysis in hydrogenation over palladium at 117-120° at 20 atm and gave products in... 

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). 

The intermediate aldimines can also be alkylated7 or used as condensing agents8 by removal of the a-hydrogen atom. The metalloaldimine is a useful intermediate for the preparation... 

Examples of the Bronsted-acid catalysts and hydrogen-bond catalysts are shown in Figure 2.1. We have recently reported the Mannich-type reaction of ketene silyl acetals with aldimines derived from aromatic aldehyde catalyzed by chiral phosphoric acid 7 (Figure 2.2, Scheme 2.6) [12]. The corresponding [5-amino esters were obtained with high syn-diastereoselectivities and excellent enantioselectivities. 

The combinahon of a stronger Bronsted acid with an electrophile bearing a basic electrophile would result in a Bronsted-acid-catalyzed reaction. Use of aldehyde in place of aldimine with neutral acid would lead to a hydrogen-bond-catalyzed reaction. 

Several years later, Corey disclosed the C2 symmetric bicyclic guanidine 19 as an effective bifunctional catalyst for the Strecker reaction (Scheme 5.40) [74]. According to the catalytic cycle, HCN should hydrogen bond to the catalyst to form guanidinium-cyanide complex A. A subsequent increase in acidity of the catalyst N—H proton allows donation of a hydrogen bond to the aldimine to form TS assembly B. Enantiofacial attack of CN to the bound aldimine gives the Strecker product. 

In previous work, Corey used the free base form of 34 as an effective chiral ligand in the Os04-promoted dihydroxylation of olefins [90]. He later found that ammonium salt 34 catalyzed the addition of HCN to aromatic N-allyl imines (Scheme 5.50) [91]. The U-shaped pocket of the catalyst is essential in fixing the orientation of the hydrogen-bonded activated aldimine via n-n interactions. 

Scheme 6.24 Amines obtained from the transfer hydrogenation of aldimines in the presence of catalyst 9 and Hantzsch ester 19.

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