Aldehydes preparation from aldimines

In 1997, Kobayashi and colleagues reported the first truly catalytic enantioselective Mannich-type reactions of aldimines 24 with silyl enolates 37 using a novel chiral zirconium catalyst 38 prepared from zirconium (IV) fert-butoxide, 2 equivalents of (R)-6,6 -dibromo-l,l -bi-2-naphthol, and N-methylimidazole (Scheme 13) [27, 28], In addition to imines derived from aromatic aldehydes, those derived from heterocyclic aldehydes also worked well in this reaction, and good to high yields and enantiomeric excess were obtained. The hydroxy group of the 2-hydroxyphenylimine moiety, which coordinates to the zirconium as a bidentate ligand, is essential to obtain high selectivity in this method. 

The vinylogous Mannich reaction of triisopyloxyfurans with aldimines prepared from aldehydes and 2-aminophenol proceeded with moderate selectivity in the presence of a catalytic amount of a Ti(IV)-BINOL complex [22]. 

Some of the problems associated with the synthesis of a-dicarbonyl starting materials have been alleviated by the use of propane-1,3-dithiol, which reacts with aldehydes to give cyclic thioacetals. With butyllithium the resulting stable dithiane anions (134) can be transformed into a-diketones or a-hydroxy ketones (Scheme 73). A further approach to such compounds is found in the reaction of a-ketonitrate esters with sodium acetate (Scheme 73), while aryl a-diketones are also available from a-ketoanils (prepared from the cyanide-ion-catalyzed transformation of aromatic aldimines) (70AHC(12)103). 

The intermediate aldimine or ketimine is prepared from the amine and the aldehyde or ketone in an organic solvent, and is usually hydrogenated without isolation. However, in some cases, the intermediate... 

Nitrilium salts (40 equation 10) can be prepared from nitriles and triethyloxonium fluoroborate. Early workers concluded that the nitrilium salts could be reduced to amines but that the reduction could not be stopped at the aldehyde (aldimine) stage.Later, it was demonstrated that reduction of the nitrilium salts with NaBH4 was rapid and did give the corresponding amine, but with triethylsilane yields of 60-90% of both aliphatic and aromatic aldehydes were obtained. Triethylsilane is a mild reagent which reduces carbocations but neutral compounds are generally not reduced and so overreduction is not a problem with this reagent. Formation of the nitrilium salts with triethyloxonium fluoroborate is slow but can be speeded up by the use of iron(III) chloride (Scheme 19). There were some notable exceptions to aldehyde formation with some aromatic nitriles. 

Aldimines, RCH=NH, cannot be prepared from the aldehyde and ammonia some polymerize (e.g., acetaldehyde gives 2,4,6-triethylhexahydro- -triazine), some condense further with the carbonyl compound (hydrobenzamide from... 

The standard procedure used for aryl aldehydes was followed using aldimines and Mn prepared from Mnl2. During the workup step, the combined oi anic layers were washed with saturated Na2S203 solution to remove iodine species from the reaction mixture. Flash chromatography (hexanes-ethyl acetate) afforded the corresponding vicinal diamines in 62 and 56% yields, respectively. 

The asymmetric syntheses of 2-alkylcyclohexanones can be effected by the alkylation of the anions of chiral imines of cyclohexanones, prepared from either chiral a-amino-acid esters or chiral polymer-bound amines. Similarly, anions of chiral phenylethyl aldimines are alkylated to give an asymmetric aldehyde synthesis. ... 

The asymmetric 1,4-addition of Grignard reagents to chiral a,/8-unsaturated aldimines (41), prepared from cycloalkenecarboxaldehydes and optically active a-amino-acid t-butyl esters, provides a new route to 2-substituted cyclic aldehydes in reasonable chemical and optical yields (Scheme 43)." ... 

The fluoboric acid-catalyzed aza-Diels-Alder reaction of aldimine and Danishefsky s diene proceeds smoothly to afford dihydro-4-pyridones in high yields [90] (Equation 4.16). Unstable aldimines generated from aliphatic aldehydes can be prepared in situ and allowed to react under one-pot reaction conditions. This one-pot Bronsted acid-catalyzed three-component aza-Diels-Alder reaction affords the adducts in good to high yields. 

In general, an aldimine is among the least reactive carbonyl compounds and is by far less reactive than an aldehyde [31-33]. Nevertheless, the Et2Zn-Ni catalytic system is successfully extended to the homoallylation of aldimine. Aldimine prepared in situ from an aldehyde and a primary aromatic amine undergoes the homoallylation smoothly under the essentially identical con-... 

In the condensation of /3-hydroxy aldehydes 303 with A -sulfonyl aliphatic aldimines 304 (which could also be prepared in situ from the aliphatic aldehyde and A -sulfinyl /i-toluenesulfonamide), 2,5,6-trisubstituted 3,6-dihydro-277-1,3-oxazines 306 were formed as single /ra r-stereoisomers (Scheme 57). No oxazine formation was observed in the... 

In contrast to the epoxides, preparative routes to the aziridines are fairly evenly split between the [C=N + C] and the [C=C + N] routes. Among contributions in the former category, aziridine carboxylate derivatives 110 can be prepared through the lanthanide-catalyzed reaction of imines with diazo compounds, such as ethyl diazoacetate (EDA). In this protocol, iV-benzyl aryl aldimines and imines derived from aromatic amines and hindered aliphatic aldehydes are appropriate substrates <99T12929>. An intramolecular variant of this reaction (e.g.. Ill —> 112) has also been reported <990L667>. 

The physical constants of several other imines prepared by a similar procedure are shown in Table X. The aldimines listed in the Table can be obtained only if certain precautions are strictly observed [4b]. The method of Emerson, Hess, and Uhle [4c] could not be extended satisfactorily and the method described in Preparation 2-2 is a modification of the one described by Chancel [4d] for propylidenepropylamine. The reaction is best carried out by adding the aldehyde to the amine, without a solvent, at 0°C. When the order of addition is reversed, the yields are much lower. Potassium hydroxide is added at the end in order to remove the water formed during the reaction. The use of other drying agents such as potassium carbonate or magnesium sulfate failed to yield aldimines on distillation. The aldimines should always be distilled from fresh potassium hydroxide to yield water-white products. The aldimines are unstable and should be used within a few hours after their distillation otherwise polymeric products are obtained. 

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. 

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