Aldehydes from aldimines

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. 

Isomerization of alkenes is catalyzed by bis(j7 -allyl)(jj -cyclopentadienyl)vanadium(IV). Cyclohexene nndergoes catalytic stereoselective aerobic oxidation with CpV(CO)4. Reductive coupling (see Reductive Coupling) of aldehydes and aldimines is catalyzed by a Cp-substituted vanadium compound in the presence of a chlorosilane and zinc or aluminum. Vanadocene or bis( ] -cyclopentadienyl)dimethylvanadium(IV) catalyzes the synthesis of 1,2-diphenyldisilane and 1,2,3-triphenyltrisilane from phenylsilane. ... 

In a later development by Bedenbaugh et methylamine was used as solvent and lithium as electron donor. No proton donor was required, suggesting that the lithium salt (28) of hemiaminal (27) is stable under the reaction conditions (both aldehydes and aldimines are reduced by the reagent cf. the analogous reduction of carboxylic acids, Section 1.12.2 and Scheme 2). Yields of aldehydes produced by this method are shown in Table 8. It is notable that only tertiary amides are reduced satisfactorily. A major limitation of the reaction is the substantial formation of side products resulting from transamid-ation by the methylamine solvent (/. e. RCONHMe from RCONR 2). 

Aldehydes from alkylmagnesium bromides.1 Aliphatic Grignard reagents react with I eq. of TMBI in THF to give aldimines ( ) which on hydrolysis (oxalic acid)... 

AUylation. Aldehydes and aldimines are converted to homoallylic alcohols and amines, respectively, by the allylindium reagent generated from allyl bromide and the metal. Starting from glyceraldehyde acetonide and related aldehydes, the chain extension followed by ozonolysis and simple manipulations allows the elaboration of 2-deoxy sugars in a straightforward manner. ... 

Synthesis of a,P-Unsaturated Aldehydes from Trimethylsilylated Aldimines... 

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. 

Oxidations of nitrogen-containing compounds [213] derived from aldehydes and ketones have been reviewed. The most common products from aldimine oxidations are nitriles [214]. However, other compounds such as nitrile oxides [215], oxaziridines [205, 216] and formamides or amides stemming from a Beckmarm rearrangement (see Beckmann reaction, under Section 9.3.2.2.) can also be formed. Furthermore, the initial aldehyde can be regenerated by oxidative deprotection [190, 217]. 

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 ... 

Decant the ethereal solution from the yellow aldimine stannichloride which has separated, rinse the solid with two 50 ml. portions of ether, and transfer the solid to a 2-5 litre flask fitted for steam distillation and immersed in an oil bath at 110-120°. Pass steam through a trap (compare Fig. 11,40, 1,6) to remove condensed water, then through a superheater heated to 260° (Fig. I, 7, 2), and finally into the mixture (2). Continue the passage of y steam until the aldehyde is completely removed (4-5 litres 8-10 hours). Filter the white soUd at the pump, and dry in the air. The resulting p-naphthaldehyde, m.p. 53-54°, weighs 12 g. It may be further purified by distillation under diminished pressure (Fig. II, 19, ) -, pour the colourless distillate, b.p. 156-158°/15 mm., while hot into a mortar and powder it when cold. The m.p. is 57- 58°, and the recovery is over 90 per cent. 

Aldehydes, general procedure (3). A solution of nilnie 1 (1 mol) in EtOAc saturated with HO gas al 0°C is added to a solution ol SnCl2 (1.1 mol) in EtOAc previously saturated wlh HCI at 0°C. After several hours at 0°C the aldimine complex (R.CHNH2 3 SnCle separated as pale yellow prisms. The complex was filtered, washed with EtjO and dried over KOH under vacuum to afford a pure sample of 2. Steam distillation of 2 gave aldehyde 3 in the distlRate if the aldehyde was volatile. Alternatively, the aldehyde was extracted from the residue of the steam distillate... 

Petrow described the formation of 3-iminoketones from 3-keto-aldehydes and aniline. Cyclization in the presence of aniline hydrochloride and ZnCh smoothly provides the desired quinoline 26. Bis-imine 24 is the proposed intermediate that undergoes cyclization. The aldimine is more reactive than the ketimine toward cyclization thus, cyclization on the aldimine occurs. When the bis-imine is not formed, partial aniline migration can occur which results in mixtures of cyclized products. 

With Aromatic Aldehydes. To a solution of 10.3 g (20 mmol) of 2,3,4,6-tetra O-pivaloyl-/ -i>galactopyra-nosylaminc in 50 rnL of /-PrOI 1 or heptane are added 30 mmol of the corresponding aromatic aldehyde and 30 drops of acetic acid. After 30 min to 2 h, the Schiff base precipitates from the /-PrOH solution. When the reaction is carried out in heptane, 2 g of Na2S04 or 3 g of 3 A molecular sieves are added after 15 min, and the mixture is filtered. On cooling to 0 °C the Schiff base crystallizes from the heptane solution. The aldimines are collected by filtration and rapidly washed with ice-cold /-PrOH or pentane, respectively. Generally, they are pure enough for further transformations. 

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. 

Reductive coupling of aldimines obtained from aromatic aldehydes and aromatic amines to generate vicinal diamines mediated by indium was carried out in aqueous ethanol (Eq. 11.59)." Small indium rods were used in this study. No side-product was observed due to unimolecular reduction. The presence of NH4CI was found to accelerate the reaction. The reaction fails completely in CH3CN, DMF, or wet DMF. The use of nonaromatic substrates also resulted in the failure of the reaction. 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

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-... 

This microwave effect is consistent with the fact that the rate-determining step may be certainly the generation of aldimine A from aldehydes and 2-amino 3-pico-line. It is in agreement with the transition state develops a dipole and, consequently more polar than the ground state. To ascertain this hypothesis, it was effectively next shown that the reaction involving reaction with preformed aldimine A, no revealed any microwave effect [119]. 

More recently, Tamaru and co-workers reported nickel-catalyzed reductive coupling of dienes with in situ-generated aldimines from aldehydes and amines (Equation (88)).446,446a The reaction exhibits high regio- and diastereoselectivity. 

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]. 

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

Akiyama et al. disclosed an asymmetric hydrophosphonylation in 2005 (Scheme 32) [55], Addition of diisopropyl phosphite (85a) to A-arylated aldimines 86 in the presence of BINOL phosphate (R)-M (10 mol%, R = 3,5-(CF3)j-C Hj) afforded a-amino phosphonates 87 in good yields (72-97%). The enantioselectivities were satisfactory (81-90% ee) in the case of imines derived from a,(3-unsaturated aldehydes and moderate (52-77% ee) for aromatic substrates. 

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