Aldehydes from imines

A Grignard type of addition of alkynes to in situ generated imines from aldehyde and amines, catalyzed by CuBr, provides an efficient solvent-free approach for the synthesis of substituted N-heterocycles such as propargyla-mines in excellent yields (Scheme 8.17). ... 

Imines. Efficient formation of imines from aldehydes and from unhindered ketones is carried out at room temperature. 

Dynamic combinatorial chemistry (DCC) has proven extremely useful in creating complex mixtures of interchanging compounds termed dynamic combinatorial libraries (DCL). Key to the formation of such DCLs is a reversible chemical process that allows the library members to interconvert. The formation of imines from aldehydes and amines is a prominent example for the creation of a DCL. Since the overall distribution of compounds is under thermodynamic control, external stimuli can be used to bias the DCL toward a specific member of the library. This approach has been exploited successfully in the search of potent receptors for molecules of pharmacological interest, the creation of supramolecular assemblies, and ligands for biomacromolecules. ... 

Stage is a dehydration and yields an imine as the isolated product. Imines from aldehydes are called aldimines, those from ketones are ketimines. 

The N-SES group can be incorporated by treating an aldehyde with iV-sulfinyl-/3-trimethylsilylethanesulfonamide (SESNSO) (13), which can be made by treating the sulfonamide (12) with thionyl chloride and a catalytic amount of M,fV-dichloro-/7-toluenesulfonamide (eq 7) (see also fV-sulfinyl-/7-toluenesulfon-amide. The iV-sulfonyl imine can be used in situ in a number of reactions. For example, the fV-sulfonyl imine from aldehyde (14) reacts with 2,3-dimethylbutadiene (eq 8) to give the Diels-Alder adduct (15). Treatment of (15) with fluoride ion affords the bicycUc lactam (16). Also, the fV-sulfonyl imine derived from isobutyraldehyde and (13) reacts with vinylmagnesium bromide to provide the allylic SES-sutfonamide (17) in 65% yield (eq 9). ... 

Most studies in this field have been on nitrones. One of the reasons for this is probably because nitrones are readily available compounds that can be obtained from aldehydes, amines, imines, and oximes [2, 11]. Moreover, most acyclic ni-... 

This review summarizes the best asymmetric methods for preparing epoxides and aziridines from aldehydes (or ketones) and imines. 

Asymmetric Synthesis of Epoxides and Aziridines from Aldehydes and Imines... 

However, only the initial formation of an imine from an aldehyde and ammonia or an amine and the subsequent proton-catalyzed addition of cyanide (path ) is in accord with the chemical... 

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 imines are prepared by 16-12. The enamine salt method has also been used to give good yields of mono a alkylation of a,P-unsaturated ketones. Enamines prepared from aldehydes and butylisobutylamine can be alkylated by simple primary alkyl halides in good yields. N-alkylation in this case is presumably prevented by steric hindrance. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

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... 

Ammonia itself yields imines, R2C=NH, with carbonyl compounds but these derivatives are unstable and react with each other to form polymers of varying size. The classical aldehyde ammonias are found to be hydrated cyclic trimers, but from aldehydes carrying powerfully electron-withdrawing substituents it is possible to isolate the simple ammonia adduct [73, cf. (72), and hydrates, p. 208, hemi-acetals,... 

The pyrrolo[3, 4 2,3]azepino[4,5,6-cd] indole-8,10-dione system can be accessed by reaction, under conditions used for the Pictet-Spengler reaction, of the imines from condensation of 3-amino-4-(3-indolyl) pyrrolin-2,5-diones with aldehydes or ketones. Cyclisation to the pyrrolo-P-carbolines did not occur under the conditions <00JHC1177>. 

Li and Wei have extended their Grignard-type methodology in water to the use of in. (////-generated imines from the corresponding aldehydes and arylamines, thus furnishing the corresponding propargylamines in a three-component one-pot procedure. 

Mannich and related readions provide one of the most fundamental and useful methods for the synthesis of p-amino carbonyl compounds, which constitute various pharmaceuticals, natural products, and versatile synthetic intermediates.1271 Conventional protocols for three-component Mannich-type readions of aldehydes, amines, and ketones in organic solvents indude some severe side reactions and have some substrate limitations, espedally for enolizable aliphatic aldehydes. The dired synthesis of P-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view. Our working hypothesis was that aldehydes could read with amines in a hydro-phobic reaction fidd created in water in the presence of a catalytic amount of a metal triflate and a surfactant to produce imines, which could then read with hydrophobic silyl enolates. 

The allenylsilane ene reaction is also well suited for the synthesis of cyclohexane rings. Jin and Weinreb have described the process of Eq. 13.55 in a synthesis of 5,11-methanomorphanthridine, an Amaryllidaceae alkaloid [64], Conversion of aldehyde 163 to imine 164 with piperonylamine took place in situ. Heating the solution of imine at reflux in mesitylene for 2 h led to cyclization through the conformer shown. The yield of 165 from aldehyde 163 was 66%. 

Secondary allylic amines 184 have been prepared from aldehydes 181 (R1 = H, Me or Ph R2 = Me, Et or H) by the following sequence treatment with an amine R3NH2 (R3 = i-Pr, t-Bu, cyclohexyl or PhCH2) yields an imine 182, which is chlorinated by N-chlorosuccinimide. Dehydrochlorination of the resulting chloro compound with potassium t-butoxide gives an allylic imine 183, which is reduced to the product by means of methanolic sodium borohydride191. 

The action of the valine derivatives 87 on the diene 86 under EtAlCU catalysis resulted in a mixture of cycloadducts 88, which on hydrolysis with aqueous methanolic sodium carbonate furnished a mixture of the dihydro-2-pyridones 89 and 90 and the esters 91 and 92. In the case of imines derived from aliphatic aldehydes, e.g. 87 (R = Pr), all four types of product were isolated, whereas imines from aromatic aldehydes, 87 (R = Ph, 3-CIC6H4 etc.), gave only the esters 91 and 92 (equation 55). All products were formed in yields of 64-84% and in high de49. 

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