Amines aliphatic aldehydes with

The procedure is modified for the reaction of preformed cyanohydrins with chiral amines39. I11 a further variation, Schiff bases of aliphatic aldehydes with optically active 1-arylalkyl-amines are transformed with liquid hydrogen cyanide to the corresponding a-aminonitrilcs, which, after acid hydrolysis, give the /V-aryUilkylamino acids. Hydrogenation then yields the a-amino acids40 41. 

An alternate to the use of Lewis acids is the employment of amine catalysts in the MBH reaction. Hatakeyama and coworkers have used the quinidine (7.164) as a catalyst in the MBH reaction of both aromatic aldehydes such as ben-zaldehyde (7.17) and aliphatic aldehydes with the acrylate (7.165). In all cases ees are high (91-99%), but yields are moderate. This amine has also been applied to the catalysis of the aza-Bayhs-HiUman reaction of methylvinyl ketone (MVK) and methyl acrylate with N-tosylarylaldimines giving the product with high ee. ... 

A number of BINOL-based bifunctional organocatalysts, for example (7.171-7.173), containing both Bronsted acidic and Lewis basic sites have been used to good effect in the asymmetric MBH reaction. The amine-thiourea (7.171) promotes the MBH reaction of aliphatic aldehydes with 2-cyclohexenone with ees ranging from 80 to 94% while both the (pyridinylaminomethyl)BINOL (7.172) and phosphine (7.173) catalyse the aza-Bayhs-Hilhnan reaction of simple a,p-carbonyls such as MVK and phenyl acrylate with N-tosyl arylaldmines with similar levels of enantioselectivity. 

The older oximes, hydrazones and imines of erythromycin are still employed as intermediates to 9-deoxo-9(S)-9-aminoerythromycin (erythromycylamine), formally the result of reductive amination of the ketone. Although it has excellent antibiotic properties, it is poorly absorbed when administered orally. In earlier efforts to overcome its poor oral bioavailability, some adducts of erythromycylamine with aldehydes and ketones were synthesized, but they were not developed for clinical use due to low blood levels after oral administration to man [30]. 9-iV-ll-O-Oxazine derivatives can be prepared by condensation of aliphatic aldehydes with erythromycylamine from a more recently prepared series of oxazines, the adduct from erythromycylamine and (2-methoxyethoxy)-acetaldehyde, named dirithromycin (see Fig. 4), was selected for clinical development on the basis of its high tissue levels [31]. 

In 2003 Barbas III et al reported the direct organocatalytic asymmetric Mannich reaction of aliphatic aldehydes with a-imino ethyl glyo grlates and tested several chiral secondary amine catalysts, among which only (S)-pro-line (1), (25,4J )-4-hydrmy-proline (trans-4) and trans-12 gave high catalytic activities and very high stereoselectivities (Scheme 11.9). ... 

The synthesis of a-aminonitriles from aldehydes, amines and trimethylsilyl cyanide can be catalysed by thallium(m) chloride. Thus, reaction of several aromatic and aliphatic aldehydes with aniline or benzylamine in the presence of 1 mol% of thallium(iii) chloride tetrahydrate in solvent-free conditions smoothly led to several a-aminonitriles in good to excellent yields (Scheme 20.1). 

Recently, Connell and coworker screened a series of chiral amine nucleophiles (90-95) for the asymmetric MBH reaction of aromatic and aliphatic aldehydes with cyclopentenone in the presence of Mgl2 (Scheme 31.29) [43], They identified Fu s planar chiral DMAP catalyst 91 as the most efficient catalyst for this asymmetric MBH reaction, affording the products 97 in good to excellent yields and moderate to excellent enantioselectivities. Both aromatic aldehydes and aliphatic aldehydes were suitable for this reaction. They also pointed out that Mgl2 as a co-catalyst could accelerate the reaction rate. 

The activated imines are obtained from aromatic amines, aliphatic aldehydes, and a-ethoxycarbamates. The reaction of aldehydes with a-(alkoxy)-p-methylallylstannanes with aldehydes in the presence of BF3 -OEt2 gives almost exclusively syn-(E)-... 

Acylation. Aliphatic amine oxides react with acylating agents such as acetic anhydride and acetyl chloride to form either A[,A/-diaLkylamides and aldehyde (34), the Polonovski reaction, or an ester, depending upon the polarity of the solvent used (35,36). Along with a polar mechanism (37), a metal-complex-induced mechanism involving a free-radical intermediate has been proposed. 

Two substituents on two N atoms increase the number of diaziridine structures as compared with oxaziridines, while some limitations as to the nature of substituents on N and C decrease it. Favored starting materials are formaldehyde, aliphatic aldehydes and ketones, together with ammonia and simple aliphatic amines. Aromatic amines do not react. Suitable aminating agents are chloramine, N-chloroalkylamines, hydroxylamine-O-sulfonic acid and their simple alkyl derivatives, but also oxaziridines unsubstituted at nitrogen. Combination of a carbonyl compound, an amine and an aminating agent leads to the standard procedures of diaziridine synthesis. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Besides direct reduction, a one-pot reductive amination of aldehydes and ketones with a-picoline-borane in methanol, in water, and in neat conditions gives the corresponding amine products (Scheme 8.2).40 The synthesis of primary amines can be performed via the reductive amination of the corresponding carbonyl compounds with aqueous ammonia with soluble Rh-catalyst (Eq. 8.17).41 Up to an 86% yield and a 97% selectivity for benzylamines were obtained for the reaction of various benzaldehydes. The use of a bimetallic catalyst based on Rh/Ir is preferable for aliphatic aldehydes. 

Organic-Base Catalyzed. Asymmetric direct aldol reactions have received considerable attention recently (Eq. 8.98).251 Direct asymmetric catalytic aldol reactions have been successfully performed using aldehydes and unmodified ketones together with chiral cyclic secondary amines as catalysts.252 L-proline and 5,5-dimethylthiazolidinium-4-carboxylate (DMTC) were found to be the most powerful amino acid catalysts for the reaction of both acyclic and cyclic ketones as aldol donors with aromatic and aliphatic aldehydes to afford the corresponding... 

Ytterbium triflate [Yb(OTf)3] combined with TMSG1 or TMSOTf are excellent reagents for the conversion of a-methyl styrene and tosyl-imines into homoallylic amides 32 (Equation (19)) (TMS = trimethylsilyl).29 These conditions produce the first examples of intermolecular imino-ene reactions with less reactive imines. Typically, glyoxalate imines are necessary. A comprehensive examination of the lanthanoid metal triflates was done and the activity was shown to directly correlate with the oxophilicity scale. The first report used preformed imines, and subsequently it was found that a three-component coupling reaction could be effected, bypassing the isolation of the intermediate imine.30 Particularly noteworthy was the successful participation of aliphatic aldehydes to yield homoallylic amines. 

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. 

Hindered aliphatic aldehydes R CIIO (R1 = i-Pr or i-Bu) react with benzotriazole and anhydrous methanolic ammonia to yield the secondary amines 115, which are transformed into the phenylated amines 116 by the action of phenyllithium. Benzotriazole, aromatic aldehydes and ammonia give the imines 117, which react with lithium aluminium hydride to form dibenzylamines 118122. 

The intensity of the molecular ion of aliphatic amines decreases regularly with increasing molecular weight. [33] Analogous general behavior has also early been noted for other compound types such as the aliphatic ethers [31], hydrocarbons [34] and aldehydes [24], and others. The reason for the low stability of amine molecular ions is their predisposition to a-cleavage. 

It has been reported by Patel and Gordon " that SPPS is limited by poor yields with hindered amines, deactivated aromatic aldehydes and slight over alkylation with aliphatic aldehydes. Johnson et al argued that because of the speed and convenience of automated SPPS, support-bound cyclization protocols are ideal for the preparation of numerous cyclo peptide analogues. 

Good yields of secondary amines are achieved using both the methods in the reactions of aromatic and aliphatic aldehydes as well as of diaUcyl ketones and cycloalkanones with aliphatic and alicyclic amines (and ammonia). Anilines give low yields, but when 2 equiv is used in the sodium hydrogen telluride method, the yields are improved. In the reaction of ammonia with aldehydes, symmetrical secondary amines are obtained, whereas glu-taraldehyde and amines lead to N-substituted piperidines. 

Naturally occurring antioxidants are present in many plants and trees such as hevea rubber. The first synthetic antioxidants were synthesized independently by Caldwell and by Winkelman and Gray by the condensation of aromatic amines with aliphatic aldehydes. 

Interestingly, persulfate reacts differently with aliphatic and aromatic amines. Aliphatic primary amines are dehydrogenated to imines and further converted to aldehydes when reacted with peroxy disulfate , whereas aromatic primary amines are oxidized to nitroso compounds using potassium persulfate in the presence of H2SO4 (equation 14) °. 

---