Aminations and Related Reactions

Electrophilic amination of carbanions, enolates and their surrogates has been reviewed.  

Aldehydes, ketones and esters, XCOCH2R (X = H, alkyl, aryl, MeO, etc.), have been directly a-aminated via copper(II) bromide catalysis. An a-bromo carbonyl species is proposed as intermediate (138), followed by nucleophilic displacement of the bromide by the amine. Done in air at ambient temperature and various solvents (DMSO is best), the intermediate (138) is proposed to generate transient XCOCH(Br)R. Amine attack, as well as giving product, releases HBr, and this - together with oxygen - converts CuBr by-product back to catalyst. 

A series of neutral ehiral bis(guanidine)iminophosphoranes (139, R = Me, Bu, Br, benzhydryl) have been prepared, and their hydrohalide salts have been characterized by X-ray crystallography. They act as organosuperbase catalysts for enantioselective (g) 

A kinetic study of reactions of 2,3-dichloro-5,6-dicyano-pflra-benzoquinone (140, DDQ) with silyl enol ethers, silyl ketene acetals, allylsilanes, enamino esters and diazomethanes has been carried out in acetonitrile and DCM, allowing correlations with nucleophilicity parameters for the latter species to be examined. These are found to be 2-5 orders of magnitude larger than expected for Single Electron Transfer processes, supporting a polar mechanism for C-C bond formation at C(5). However, rate constants for (9-attack do correlate well with calculated values assuming rate-determining SET. 

Ab initio methods have been used to study the reaetion of urea with formaldehyde.  

Intra- and inter-molecular asymmetric hydroamination reactions have been reviewed.  

Aliphatic aldehydes (R CH2CH2CHO) are efficiently a-aminated by secondary amines (R R NH, R or R = benzyl or alkyl), using copper(I)/t-butyl hydroperoxide in methanol/acetonitrile at 40 °C the product is obtained in the form of the acetal, R1CH2CH(NR2r3)-CH(OMc)2.  

Branched and hindered aldehydes have been enantioselectively Q -aminated in high yield in THF solution at 0°C with azodicarboxylates, using a simple amino acid catalyst such as 3-(l-naphthyl)alanine, as its hydrochloride. An ion-pair catalyst formed by mixing a cinchona-derived diamine and camphor-sulfonic acid gives high yield and ee in direct amination of a-branched aldehydes, using azodicarboxylates.  

Combined experimental and computational studies of the a-amination of aldehydes catalysed by prolinate salts support an enamine carboxylate intermediate in the stereodetermining step.  

An amino-quinine catalyses Q -ammation of a,o -disubstituted aldehydes in good yields and up to 99% ee, giving or-hydrazino aldehydes with a quaternary stereogenic 

---

A novel synthetic approach to pep- 23 tides by computer planned stereo- (30) selective four-component condensations of a-ferrocenylalkyl-amines and related reactions... 

In 2008, Application of CyclopaUadated Compounds as Catalysts for Heck and Sonogashira Reactions, by Najera and Alonso [110], Palladacyclic Precatalysts for Suzuki Coupling, Buchwald-Hartwig Amination and Related Reactions Bedford [111]... 

Synthetic Aspects of Metal-Catalyzed Oxidations of Amines and Related Reactions. 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

The reactions of phosphorus pentachloride and diphenyltrichloro-phosphorane with amines and related compounds are reported in Chapter 9. The n.m.r. spectra of phosphine-phosphorus pentafluoride adducts have been described (see Chapter 11 for details). 

In each type of chemical reaction, the skeleton of the product is characteristic, and only its substituents can be ditferent, whereas in the U-4CR and related reactions of the isocyanides the skeleton of the products can also include different types of amines and acid components. This is illustrated by the eight skeletally different products in Scheme 1.7. Besides these compounds, many other types of compounds also can be prepared by the U-4CR. 

Abstract Several bismuth-catalyzed synthetic reactions, which proceed well in aqueous media, are discussed. Due to increasing demand of water as a solvent in organic synthesis, catalysts that can be used in aqueous media are becoming more and more important. Although bismuth Lewis acids are not very stable in water, it has been revealed that they can be stabilized by basic ligands. Chiral amine and related basic ligands combined with bismuth Lewis acids are particularly useful in asymmetric catalysis in aqueous media. On the other hand, bismuth hydroxide is stable and works as an efficient catalyst for carbon-carbon bond-forming reactions in water. 

Tuazon, E. C., R. Atkinson, S. M. Aschmann, and J. Arey, Kinetics and Products of the Gas-Phase Reactions of 03 with Amines and Related Compounds, Res. Chem. IrUermed., 20, 303-320 (1994). 

As mentioned above, it is difficult to find organic compounds which are suitable as redox catalysts for oxidations. This is the case because organic cation radicals, which are mostly the active forms in indirect electrochemical oxidations, are usually easily attacked by nucleophiles, thus eliminating them from the regenerative cycle. Therefore, the cation radicals must be stabilized towards the reaction with nucleophiles. Nelson et al. demonstrated that the cation radicals of triaryl amines and related compounds are very stable if the para positions of the aryl... 

A variety of heterocycles can be prepared from the reaction of bifunctional amines and related compounds with 1,3,5-triazine (equation 3). Similarly, 1,2,4-triazole is formed from hydrazine hydrochloride (Scheme 9) <63AG(E)309). 

These and related reactions are discussed in further detail in the following sections. For your convenience, a tabular summary of methods for the synthesis of amines appears in Tables 23-6 and 23-7. 

Surprisingly, the catalytic potential of proline (1) in asymmetric aldol reactions was not explored further until recently. List et al. reported pioneering studies in 2000 on intermolecular aldol reactions [14, 15]. For example, acetone can be added to a variety of aldehydes, affording the corresponding aldols in excellent yields and enantiomeric purity. The example of iso-butyraldehyde as acceptor is shown in Scheme 1.4. In this example, the product aldol 13 was obtained in 97% isolated yield and with 96% ee [14, 15]. The remarkable chemo- and enantioselectivity observed by List et al. triggered massive further research activity in proline-catalyzed aldol, Mannich, Michael, and related reactions. In the same year, MacMillan et al. reported that the phenylalanine-derived secondary amine 5 catalyzes the Diels-Alder reaction of a,/>-un saturated aldehydes with enantioselectivity up to 94% (Scheme 1.4) [16]. This initial report by MacMillan et al. was followed by numerous further applications of the catalyst 5 and related secondary amines. 

The reaction between (CH3)3 A1 and HNF2 appears to produce a 1 1 adduct at —80° C. which liberates CH4 slowly at this temperature. This elimination reaction, typical of the behavior of (CH3)3 A1 with secondary amines and related bases (1), probably occurs via the coordination compound, which, although not isolated, appears to be moderately stable at —80° C. The mass balance seems to indicate that only one mole of HNF2 can react at this temperature. In fact even at room temperature only two moles of methane are displaced by HNF2. The assumed reaction agrees well with the HNF2-CH4 balance ... 

Swan. G. A., Studies of the reaction of benzoyl peroxide with N,N-disubstituted aromatic amines and related compounds. V, J. Chem. Soc. C, 2880, 1971. 

J. F. Hartwig, Palladium-Catalyzed Amination of Aryl Halides and Related Reactions, in Handbook of Organopalladium Chemistry for Organic Synthesis , ed. E. Negishi, John Wiley Sons, Hoboken, NJ, 2002, p. 1051. 

Trichlorotitanium enolates are directly prepared from a ketone, TiCU, and a tertiary amine [122,123] and undergo aldol reactions with aldehydes [124-129], ketones [129], and imines [130,131], Intramolecular condensation with esters is also known [132-137], Although these reactions, based on a titanium enolate [16], which often results in high diastereoselectivity in aldol and related reactions [122], will not be discussed in detail in this article, the success of the alkylation of this titanium enolate with SNl-active electrophiles should be discussed owing to the high Lewis acidity of the metal center [123], Equation (37) shows stereoselective alkylation with an orthoacetate, which is usually inert to alkali metal enolates [138], Aminoalkylation of trichlorotitanium enolates with (a-chloroalkyl)amine has been performed analogously [139,140],... 

Fig. 4-17. Reactions of ferrocenylalkyl amines and related compounds at chiral carbon.

The Mannich and related reactions provide one of the most fundamental and useful methods for the synthesis of y -amino ketones and esters [46]. Although the classical protocols include some severe side reactions, new modifications using preformed iminium salts and imines have improved the process. Some of these materials are, however, unstable and difficult to isolate, and deaminations of the products that occur under the reaction conditions still remain as problems. The direct synthesis of /5-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view [47, 48]. Our working hypothesis is that aldehydes could react with amines in the hydrophobic micellar system in the presence of a catalytic amount of lanthanide triflate and a surfactant to produce imines, which could react with hydrophobic silyl enolates [49]. 

Catalytic asymmetric aza MBH reactions and related reactions provide a direct and efficient synthetic approach to a variety of functionalized nonamino acid derived chiral amines under mild conditions. These novel chiral amines can be directly used to prepare many other useful chiral building blocks in organic synthesis. A variety of transformations of the chiral aza MBH adducts were recently demonstrated by Raheem and Jacobsen (Scheme 13.30) [9]. 

---