Amines, metal catalyzed

Method 2. Alcohol amination—metal catalyzed amination of an alcohol over a metal catalyst under reducing conditions. 

Azetidines are compounds of interest in the field of agricultural and pharmaceutical chemistry. They are also useful as monomers and cross-linkers in polymer industry. Due to ring strain associated with it, azetidines are also useful S5mthons in organic chemistry. The common methods for S5mthesis of azetidines are cyclizations of y-amino alcohols, y-amino halides, 3-amino allenes, reactions of 1,3-dielectrophiles with amines, metal-catalyzed cyclizations in diazocarbonyls, cycloaddition reactions, and reduction of 2-azetidinones. There are several reports in literature on the S5mthesis of azetidines in aqueous media. A diastereoselective synthesis of azetidines is reported by the reaction of azazirconacyclopentane derivatives with iodine followed by treatment with aqueous potassium carbonate [26]. 

Transition metal-catalyzed synthesis of hetarylamines and hetaryl ethers from triflates and aryl/hetaryl halides or heterocyclic amines 98AG(E)2046. 

The Suzuki reaction has been successfully used to introduce new C - C bonds into 2-pyridones [75,83,84]. The use of microwave irradiation in transition-metal-catalyzed transformations is reported to decrease reaction times [52]. Still, there is, to our knowledge, only one example where a microwave-assisted Suzuki reaction has been performed on a quinolin-2(lH)-one or any other 2-pyridone containing heterocycle. Glasnov et al. described a Suzuki reaction of 4-chloro-quinolin-2(lff)-one with phenylboronic acid in presence of a palladium-catalyst under microwave irradiation (Scheme 13) [53]. After screening different conditions to improve the conversion and isolated yield of the desired aryl substituted quinolin-2( lff)-one 47, they found that a combination of palladium acetate and triphenylphosphine as catalyst (0.5 mol %), a 3 1 mixture of 1,2-dimethoxyethane (DME) and water as solvent, triethyl-amine as base, and irradiation for 30 min at 150 °C gave the best result. Crucial for the reaction was the temperature and the amount of water in the... 

Since the hydrogenation is a metal-catalyzed reaction, it is appropriate to use an oxide support to enhance the dispersion. However, the support, like the metal, needs to be chosen with the desired selectivity in mind. The early view [5] that the selectivity in nitrile hydrogenation is determined largely by the behaviour of the partially-hydrogenated intermediate, the imine R-CH = NH, which can either accept two further hydrogens to form the primary amine or can react with an already-formed amine to start a sequence which... 

Some other examples of metal-catalyzed substitutions are given in Scheme 11.10. Entries 1 to 3 are copper-catalyzed reactions. Entry 1 is an example of arylation of imidazole. Both dibenzylideneacetone and 1,10-phenanthroline were included as ligands and Cs2C03 was used as the base. Entry 2 is an example of amination by a primary amine. The ligand used in this case was (V,(V-diethyl sal icyl amide. These conditions proved effective for a variety of primary amines and aryl bromides with both ERG and EWG substituents. Entry 3 is an example of more classical conditions. The target structure is a phosphodiesterase inhibitor of a type used in treatment of asthma. Copper powder was used as the catalyst. 

Combinatorial approach to unsymmetrically tiered macromolecules [214] is a brand new area of research which would allow dendrimerization of materials (e. g., glass, classical polymers, fibers) and thus enable fine tuning of macromole-cular properties. For example, treatment of an amine terminated dendrimer with a mixture of complementary, isocyanate-based monomers [215, 216] affords a heterogeneous surfaced dendrimer. Selective transformation of the surface nitrile moieties via metal-catalyzed reduction to obtain a new polyamine dendrimer allows further combinatorial-based elaboration as illustrated in Fig. 42. 

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

In a different approach a super-high-throughput ee-assay was developed on the basis of chirally modified capillary array electrophoresis (CAE).90 CAE was used in the Human Genome Project, and commercially available instruments have been developed which comprise a high number of capillaries in parallel, for example the 96-capillary unit MegaBACE consisting of 6 bundles of 16 capillaries.91 The system can address a 96-well microtiter plate. It was adapted to perform ee-determinations of chiral amines, which are potentially accessible by catalytic reductive amination of ketones, transition metal catalyzed Markovnikov addition of ammonia, or enzymatic hydrolysis of acetamides (Scheme 14).90... 

Dissolve the sulfhydryl-containing protein or macromolecule to be modified at a concentration of l-10mg/ml in 50mM Tris, 0.15M NaCl, 5mM EDTA, pH 8.5. EDTA is present to prevent metal-catalyzed oxidation of sulfhydryl groups. The presence of Tris, an amine-containing buffer, should not affect the efficiency of sulfhydryl modification. Not only do amines generally react slower than sulfhydryls, the amine in Tris buffer is of particularly low reactivity. If Tris does pose a problem, however, use 0.1M sodium phosphate, 0.15M NaCl, 5mM EDTA, pH 8.0. 

The transition metal-catalyzed C-H insertion reaction of carbenes to organic compounds is a well-established synthetic method, as shown in the first two sections in this chapter. However, nitrene C-H insertion, the corresponding reaction of carbene analog, is much less known. In the past decade, considerable advances have been made in the development of this chemistry into a generally useful C-H amination process by using improved catalysts and protocols, in which readily available amines or amides are used as the starting substrates. Moreover,... 

An important variant for transition metal-catalyzed carbon-nitrogen bond formation is allylic substitution (for reviews, see1,la lh). Nucleophilic attack by an amine on an 7r-allyl intermediate, generated from either an allylic alcohol derivative,2 16,16a 16f an alkenyloxirane,17-19,19a-19d an alkenylaziridine19,19a 19d, or a propargyl alcohol derivative,21,21a 21d gives an allylic amine derivative. 

The synthesis of alcohols, ethers, and ketones by metal-catalyzed addition of water or alcohols to alkenes and alkynes is a well-established reaction in organic chemistry. Many regio- and stereoselective modifications of these reactions are known. In contrast, the analogous addition of ammonia or primary and secondary amines to nonactivated alkenes and alkynes has not had a comparable development, in spite of extensive efforts. In this section, we summarize the recent results of amination to unsaturated compounds. 

In addition to alkenes and alkynes, allenes have attracted considerable interest due to their unique reactivity and multireaction sites. Therefore, transition-metal-catalyzed nucleophilic addition reaction of amines and imines to allenes has been extensively studied to prepare biologically important amines and nitrogen-heterocycles.31,31d... 

In contrast to the amines, inversion of configuration for phosphines is generally negligibly slow at ambient temperature. This property has made it possible for chiral phosphines to be highly useful as ligands in transition metal-catalyzed asymmetric syntheses. 

Ylide formation, and hence X-H bond insertion, generally proceeds faster than C-H bond insertion or cyclopropanation [1176], 1,2-C-H insertion can, however, compete efficiently with X-H bond insertion [1177]. One problem occasionally encountered in transition metal-catalyzed X-H bond insertion is the deactivation of the (electrophilic) catalyst L M by the substrate RXH. The formation of the intermediate carbene complex requires nucleophilic addition of a carbene precursor (e.g. a diazocarbonyl compound) to the complex Lj,M. Other nucleophiles present in the reaction mixture can compete efficiently with the carbene precursor, or even lead to stable, catalytically inactive adducts L M-XR. For this reason carbene X-H bond insertion with substrates which might form a stable complex with the catalyst (e.g. amines, imidazole derivatives, thiols) often require larger amounts of catalyst and high reaction temperatures. 

A diverse group of secondary and tertiary amines are readily synthesized from the reaction of primary and secondary amines with allylic carbonates in the presence of preformed iridium metalacycles, but the direct synthesis of primary amines via iridium-catalyzed allylic amination requires the use of ammonia as a nucleophile. The asymmetric allylation of ammonia had not been reported until very recently, and it is not a common reagent in other metal-catalyzed reactions. Nonetheless, Hartwig and coworkers developed the reactions of ammonia with allylic carbonates in the presence of la generated in situ [89]. Reactions conducted in the initial work led exclusively to the products from diallylation (Scheme 16). Further advances in... 

The use of ethylene adduct lb is particularly important when the species added to activate catalyst la is incompatible with one of the reaction components. Iridium-catalyzed monoallylation of ammonia requires high concentrations of ammonia, but these conditions are not compatible with the additive [Ir(COD)Cl]2 because this complex reacts with ammonia [102]. Thus, a reaction between ammonia and ethyl ciimamyl carbonate catalyzed by ethylene adduct lb produces the monoallylation product in higher yield than the same reaction catalyzed by la and [Ir(COD)Cl]2 (Scheme 27). Ammonia reacts with a range of allylic carbonates in the presence of lb to form branched primary allylic amines in good yield and high enantioselectivity (Scheme 28). Quenching these reactions with acyl chlorides or anhydrides leads to a one-pot synthesis of branched allylic amides that are not yet directly accessible by metal-catalyzed allylation of amides. 

Lazar, M. and Angelici, R.J. (2005) Gold metal-catalyzed reactions of isocyanides with primary amines and oxygen analogies with reactions of isocyanides in transition metal complexes. J. Am. Chem. Soc., 128, 10513. 

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