Amination of carbonyl compounds

Compound 14b catalyzed the aziridination of aliphatic and aromatic a,P-unsaturated aldehydes with similar results to catalyst 14a [15]. Worse results were achieved by using catalyst 14c in the synthesis of terminal N-tosylaziridines [16]. The further oxidation of products 15 allowed the synthesis of chiral p-amino esters derivatives [14—16], whereas their reduction permitted the synthesis of chiral protected amino alcohols [16]. 

A mechanistic rationalization of the unusual product-acceleration behavior observed for the proline-catalyzed a-amination of linear aldehydes (19a, = H) 

Recently, DFT calculations showed that in this proline-catalyzed process an enamine carboxylic acid mediated transition model rules under base-free conditions, giving the expected product stereochemistry, while an enamine carboxylate pathway operates in the presence of base, leading to the opposite enantiomer [23]. 

Complex molecules have also been synthesized by sequential use of the orga-nocatalytic a-amination of aldehydes by azodicarboxylates catalyzed by some of the systems shown above and by other reaction processes, such as the Passerini reaction [40], Homer-Wadsworth-Emmons olefination [41], Wittig olefination [42], and allylation reaction followed by a ring-closing metathesis [43], In addition, the combination of catalysts in cycle-specific organocascade processes [44] has allowed the synthesis of chiral complex molecules with good results. 

The organocatalyzed a-amination reaction using azodicarboxylates can be also performed using ketones as substrates. Thus, silyloxyproline 39 promoted the 

This synthesis works especially well with cyclohexanone giving 80% oxaziridines with either chloramine (77JPR195) or (V-chloromethylamine. Simple aliphatic ketones and ortho substituted aromatic aldehydes yield 30-50% oxaziridines with N-chloromethylamine (65CB2516). 

Compound (253) is formed from benzaldehyde and methylhydroxylamine-O-sulfonic acid in 35% yield. With ethyl-substituted chloramine or hydroxylamine-O-sulfonic acid yields do not exceed 10%, which is assumed to be due to steric hindrance and is foreseeable for both carbonyl addition and O —N bond formation. 

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The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

Tab. 3.8 Microwave-mediated Leuckart reductive amination of carbonyl compounds in 30 min.

Sodium cyanoborohydride [123], sodium triacetoxyborohydride [124] or NaBH4 coupled with sulfuric acid [125] are common agents used for the reductive amination of carbonyl compounds. These reagents either generate waste or involve the use of corrosive acids. The environmentally friendlier procedures developed by Varma and coworkers have been extended to a solvent-free reductive amination protocol for carbonyl compounds using moist montmorillonite K 10 day supported sodium borohydride that is facilitated by microwave irradiation (Scheme 6.39) [126]. 

The practical applications of NaBH4 reductions on mineral surfaces for in situ generated SchifFs bases have been successfully demonstrated. The solid-state reductive amination of carbonyl compounds on various inorganic solid supports such as alumina, clay, silica etc. and especially on K 10 clay surface rapidly afford secondary and tertiary amines [126]. Clay behaves as a Lewis acid and also provides water from its interlayers thus enhancing the reducing ability of NaBH4 [22],... 

Reductive amination, of carbonyl compounds, 16 573 Reductive bleaching, 21 440 Reductive dechlorination defined, 3 757t Reductive dehalogenation defined, 3 757t... 

Reductive amination of carbonyl compounds, 59, 1 71, 1 Reductive cyanation, 57, 3 Redutive desulfonylation, 72, 2 Reductive desulfurization of thiol esters,... 

This chapter on electrophilic amination using O-substituted hydroxylamines 1-5 and oximes 7 is focused on the various methods that have been reported for the amination of carbon nucleophiles. Synthetic aspects and applications of the methods for C—N bond formation are accompanied by a brief discussion of the reaction mechanisms. The preparation of O-substituted hydroxylamines and oximes has not been considered in detail. This review covers the literature up to August 2007 and is partly based on reviews on the electrophilic amination of carbanions and a-amination of carbonyl compounds. ... 

Varma, R.S. and Dahiya, R., Sodium borohydride on wet clay solvent-free reductive amination of carbonyl compounds using microwaves, Tetrahedron, 1998, 54, 6293-6298. 

The C=N bonds of imines, oximes and hydrazones can be hydrogenated to form the corresponding amines even under ambient conditions on Pt, Pd, Rh and Raney Ni catalysts in acidic, neutral or basic media (equation 42). The imines, furthermore, are intermediates in the hydrogenation of nitro compounds, nitriles and oximes, and likewise play a key role as intermediates in the reductive amination of carbonyl compounds. 

Addition to N=N double bonds (a-amination of carbonyl compounds) [7.1]... 

A solvent-free reductive amination of carbonyl compounds using sodium borohydride supported on moist montmorillonite K10 clay also was facilitated by microwave irradiation (Scheme 8) [54]. Clay served the dual purpose of a Lewis acid and provided water from its interlayers to enhance the reducing ability of NaBH4. 

The reduction of 2-imino ketones is performed with Bu2SnClH-HMPA to give 2-amino ketones where no reduction of the carbonyl group takes place.84 The reductive amination of carbonyl compounds is one of the most convenient routes to various secondary amines. The high imine selectivity of Bu2SnClH-HMPA can be applied to... 

The two most general amine syntheses are the reductive amination of carbonyl compounds and the reduction of amides. Show how these techniques can be used to accomplish the following syntheses. 

Reductive amination of carbonyl compounds. Sodium cyanoborohydride has been the reductant of choice for this reaction, even though it is highly toxic (4, 448-449). Borane-pyridine is recommended as a nontoxic substitute. The reactions are conducted in acetic acid, in which this borane is fairly stable, and a co-solvent such as CH2CI2 or THE... 

Reductive amination of carbonyl compounds. This reagent effects reductive ami-nation of aldehydes or ketones with amines (equation 1). Yields tend to be only moderate with anilines, but are high with aliphatic amines. 

Reductive amination of carbonyl compounds with ammonia or amines in the presence of a reducing agent has been discussed (method 431). When the reducing agent is formic acid or a derivative, the products are the formyl derivatives of primary or secondary amines or the formates of tertiary amines. These intermediates readily furnish the amines, A critical discussion of the reaction along with experimental conditions and procedures and a tabular survey of compounds has been presented. ... 

Stereospecific Reductive Amination of Carbonyl Compounds. Catalytic or chemical reduction of chiral imines derived from (1) often proceeds with high diastereoselectivity. Reductive removal of the a-methylbenzyl group yields chiral primary amines (eq 18 and 19). - ... 

Another method for reductive amination of carbonyl compounds is based on the electroreduction of oximes in aqueous media. Thus, sugar oximes were reduced to their corresponding glycamines in good yields (Hg, KCl, acetate buffer). Similar reductions of oximes derived from furfural, salicylaldehyde, benzophenone and cyclohexanone have also been described, " but reports of preparative electrolyses in strictly aprotic media seem to be absent in the literature. 

Sodium triacetoxyborohydride Na[BH(OAc)3] ° and hydrogenation (H2, Pd/C) are used as alternatives to sodium cyanoborohydride for the reductive amination of carbonyl compounds. Also, Zn[BH4]2 is a particularly effective agent for the reductive amination of a,p-unsaturated aldehydes and ketones. ... 

Reduction ofimines. A mixture of Bu SnClj and Bu SnHj generates BujSnfCljH which saturates imines when complexed with HMPA. Thus, a-amino ketones are obtained from the corresponding imino ketones. Direct reductive amination of carbonyl compounds is also achieved (11 examples, 70-99%). ... 

Secondary amines. The reductive amination of carbonyl compounds with MeNHj HCl is easily accomplished. Triediylamine is present in the reaction mixture. 

Reductive amination of carbonyl compounds (including those belonging to heterocyclic series) with borohydride- and borane-reducing agents 02OR(59)l. 

Reductive amination of carbonyl compounds. Method A. N-octylbenzylamine (typical procedure). AAMF (30 mL) suspension of benzylamine (1.67 g, 15 mmol), octanal (1.55 g, 15 mmol), EtjN (7.0 mL, 50 mmol) and Al2Te3 (6.1 g, 14 mmol) is refluxed. The reaction is monitorized by GLC and H2O (3 mL, 168 mmol) is added at 15°C after 30 min. The het-erogeneons mixtnre is refluxed for another 30 min. The black solid is removed by filtration and the filtrate dried (CaCOj) and evaporated. The residne is distilled, giving the prodnct (2.7 g (80%) b.p. 108-112°C/1 torr). 

Riermeier, T, Haack, K. J., Dingerdissen, U., Boerner, A., Tararov, V., and Kadyrov, R. (2005) Method for producing amines by homogeneously catalyzed reductive amination of carbonyl compounds, U.S. Patent No. 6884887, Degussa AG, Germany. 

Acyloxaziridines are easily obtained from compounds unsubstituted at nitrogen by reaction with acid chlorides or isocyanates. Acylation proceeds so smoothly that, in the amination of carbonyl compounds, oxaziridine compounds are obtained in better yields on addition of acid chlorides than in the absence of the acylating agent. With aliphatic aldehydes, amination does not succeed at all except in the presence of benzoyl chloride. Proof of structure comes from reduction by iodide to give the acid amide and carbonyl compound. 

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