Amination of Ketones and Aldehydes

Both yield and enantioselectivity of the reaction were good, and the reaction proceeded at an acceptable rate. The aminoxylated products 29 can be 

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A dynamic kinetic resolution has been employed to achieve a catalytic asymmetric reductive amination of aldehydes.332 Reductive amination of ketones and aldehydes by sodium triacetoxyborohydride has been reviewed, highlighting its advantage over other reagents.333... 

Reductive amination of ketones and aldehydes is one of the best methods for synthesizing amines (Section 19-18). It also forms amino acids. When an a-ketoacid is treated with ammonia, the ketone reacts to form an imine. The imine is reduced to an amine by hydrogen and a palladium catalyst. Under these conditions, the carboxylic acid is not reduced. 

Pienemann T, Sch er H-J (1987) Reductive amination of ketones and aldehydes at the mercury cathode. Synthesis 1987 1005-1007 Gomez JRO (1991) Electrosynthesis of N-methylhydroxylamine. J Appi Eiectrochem 21 331-334... 

Inspired by the work of Burk and Feaster ) we attempted to use (2-pyridyl)hydrazine (4.36) as a coordinating auxiliary (Scheme 4.10). Hydrazines generally react effidently with ketones and aldehydes. Hence, if satisfactory activation of the dienophile can be achieved through coordination of a Lewis acid to the (2-pyridyl)hydrazone moiety in water. Lewis-add catalysis of a large class of ketone- and aldehyde-activated dienophiles is antidpated Subsequent conversion of the hydrazone group into an amine functionality has been reported previously by Burk and Feaster ... 

The nitrogen analogs of ketones and aldehydes are called imines, azomethines, or Schiff bases, but imine is the preferred name and we use it here. These compounds can be prepared by condensation of primary amines with ketones or aldehydes.102 The equilibrium constants are unfavorable, so the reaction is usually driven forward by removal of water. 

Oxidation is the first step for producing molecules with a very wide range of functional groups because oxygenated compounds are precursors to many other products. For example, alcohols may be converted to ethers, esters, alkenes, and, via nucleophilic substitution, to halogenated or amine products. Ketones and aldehydes may be used in condensation reactions to form new C-C double bonds, epoxides may be ring opened to form diols and polymers, and, finally, carboxylic acids are routinely converted to esters, amides, acid chlorides and acid anhydrides. Oxidation reactions are some of the largest scale industrial processes in synthetic chemistry, and the production of alcohols, ketones, aldehydes, epoxides and carboxylic acids is performed on a mammoth scale. For example, world production of ethylene oxide is estimated at 58 million tonnes, 2 million tonnes of adipic acid are made, mainly as a precursor in the synthesis of nylons, and 8 million tonnes of terephthalic acid are produced each year, mainly for the production of polyethylene terephthalate) [1]. 

Oxidoreductases are, after lipases, the second most-used kinds of biocatalysts in organic synthesis. Two main processes have been reported using this type of enzymes-bioreduction of carbonyl groups [39] and biohydroxylation of non-activated substrates [40]. However, in recent few years other processes such as deracemization of amines or alcohols [41] and enzymatic Baeyer-Villiger reactions of ketones and aldehydes [42] are being used with great utility in asymmetric synthesis. 

Various approaches can be used to synthesize pyridines and partially saturated pyridines on insoluble supports. Dihydropyridines can be readily prepared by cyclocondensation of amines with ketones and aldehydes (Hantzsch pyridine synthesis, Figure 15.12). This synthesis proceeds particularly smoothly when using a 3-keto carboxylic acid derivative as the ketone component. This cyclocondensation has been realized on... 

Tertiary amines are oxidized to the corresponding nitrogen oxides. Tosyl hydrazones of ketones and aldehydes and imines are oxidized to the corresponding carbonyl compounds. Reactions have been carried out with small molecules and also with molecules that would not diffuse into the pore structure of the titanium silicates. As in the case of C—C bond cleavage, it is possible that these reactions take place on the outer surface of the catalyst crystals. 

Amino acids used by the human body are a-amino acids. They are called alpha-amino adds bt cause the amine group is attached to the carbon which is alpha to the carbonyl carbon, similar to a-hydrogens of ketones and aldehydes. 

Key Mechanism 18-5 Formation of Imines 851 18-16 Condensations with Hydroxylamine and Hydrazines 853 Summary Condensations of Amines with Ketones and Aldehydes 854 18-17 Formation of Acetals 855... 

Reactions of Amines with Ketones and Aldehydes (Review) 895... 

In Section 18-15, we saw that amines attack ketones and aldehydes. When this nucleophilic attack is followed by dehydration, an imine (Schiff base) results. The analogous reaction of a hydrazine derivative gives a hydrazone, and the reaction with... 

Predict the products of reactions of amines with ketones and aldehydes, alkyl halides and tosylates, acid chlorides, sulfonyl chlorides, nitrous acid, and oxidizing agents. Propose mechanisms where appropriate. 

Enantioselective Alkylation. Both antipodes of this chiral amine have been used in the enantioselective alkylation of ketones and aldehydes via their respective chiral, nonracemic lithioe-namines (eq 1). The enantioselectivity in alkylation results from the induced rigidity of the lithioenamine upon chelation with the methoxy group, providing the bias necessary to influence the direction and rate of entry of the electrophile. 

The equilibrium existing in an aqueous medium between a Schiff base and its corresponding aldehyde or ketone can be exploited in reductive aminations, as shown recently by Pienemann and Schafer. Because of its slightly more positive reduction potential compared to a carbonyl group, the Schiff base can be selectively reduced in a controlled potential electrolysis, to yield an amine in high yields, as shown in equation (8). This method is applicable to a variety of ketones and aldehydes. 

For applications of enamines as reactive derivatives of ketones and aldehydes, the major structural question for those derived from unsymmetrical ketones is that of regiochemistry. The ratio of less to more substituted forms for a series of 10 enamines derived from various amines and methylcyclohexa-none has been summarized by Thompson from various literature studies (Scheme 5). ... 

The two major synthetic applications of imine derivatives of ketones and aldehydes are (i) for reduction to amines and (ii) for formation of carbon-carbon bonds at the a-position to the original carbonyl group. Both topics are covered extensively in other volumes in this series and thus will be treated only briefly here. 

Prior to the discoveries that lithium and other less electropositive metal cations were valuable counterions for enolate alkylations, the Stork enamine reaction was introduced to overcome problems such as loss of regioselectivity and polyalkylation that plagued attempts to alkylate sodium or potassium enolates of ketones or aldehydes.Methods of synthesis of enamines by reactions of ketones and aldehydes with secondary amines have been thoroughly reviewed.Enamine alkylations are usually conducted in methanol, dioxane or acetonitrile. Enamines are ambident nucleophiles and C- and V-alkylations are usually competitive. Subsequent hydrolysis of the C-alkylated product (an iminium salt) yields an... 

Selenolates such as Na2Se, NaSeH, PhSeNa, etc., and tellurolates such as NapTe, NaTeH, PhTeNa, etc., are excellent nucleophiles and can reduce a variety of functional groups by nucleophilic attack or single electron-transfer. On treatment with alkali metal selenolates (or amine salts of HpSe and PhSeH), reduction or reductive selenation of ketones and aldehydes, C=C reduction of a,/l-unsaturated compounds, and reduction of nitrogen compounds such as nitro compounds occur successfully [118, 176]. Compared with these selenolate anions, the corresponding tellurium compounds are highly reactive not only toward the same substrates but also toward halo compounds such as a-bromo ketones and vic-dibromoalkanes [46, 52, 177]. 

A significant improvement in the alkylation of ketone and aldehyde enamines involves the use of sterically hindered amines . N-Alkylation is prevented with consequent increase in C-alkylation. For example, reaction of the -butylisobutylamine enamine of cyclohexanone (29) with methyl iodide in boiling acetonitrile (Scheme 16), or trimethy-loxonium tetrafluoroborate at room temperature gave 2-methylcyclohexanone in increased yields of 56% and 74%, respectively (compare Scheme 10). 

The strategies presented in Table 8.1 can be generalized in the following manner (1) carbanion addition to aldimine or ketimine derivatives (2) sequential amination-alkylation of aldehydes (carbanion addition to in situ formed aldimine derivatives) (3) transfer hydrogenation or hydrogenation of imines (4) reductive amination of ketones and (5) N-acetylenamide reduction. Because of the difficulty of their synthesis, a-alkyl,-alkyl substituted amines are highlighted whenever possible. 

In 1885, R. Leuckart reported that the reaction of ammonia and primary or secondary amines with ketones (and aldehydes) was possible with ammonium formate, to produce the corresponding primary, secondary, or tertiary amine.1 This reaction became known as the Leuckart reaction. In 1891, Wallach reported that the use of excess formic acid led to an improvement in yield, and that the reaction could be carried out at lower temperatures.2 The Leuckart-Wallach reaction was bom. Wallach went on to apply this reaction to a wide variety of carbonyl compounds, including alicyclic and terpenoid ketones.5... 

The mechanistic pattern of hydration and alcohol addition reactions of ketones and aldehydes is followed in reactions of carbonyl compounds with amines and related nitrogen nucleophiles. These reactions involve addition and elimination steps proceeding through tetrahedral intermediates. These steps can be either acid catalyzed or base catalyzed. The rates of the reactions are determined by the energy and reactivity of the tetrahedral intermediates. With primary amines, C=N bond formation ultimately occurs. These reactions are reversible and the position of the overall equilibrium depends on the nitrogen substiments and the structure of the carbonyl compound. 

Photoreaclion of ketones and aldehydes in the presence of amines involves charge transfer interactions between amines and... 

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