Regioselective amination

Related alkyne couplings yield tricyclic quinolines via a regioselective amination/C-H functionalization pathway (Equations (104) and (105)).98... 

A highly regioselective amination of 6-aryl-2,4-dichloropyrimidines has been developed using palladium catalysis. The reaction which works well with secondary aliphatic amines and with anilines gives the 4-substituted products.46 Palladium catalysis has also been used in the regioselective coupling of 2,3-dibromopyridine with a series... 

The regioselective amination of 2,3-dihydrofuran with morpholine catalyzed by palladium thiocyanate diphosphine complexes (45 turnovers)102, and the regioselective addition of aniline to acrylonitrile and analogous electron-poor alkenes catalyzed by dialkylpalladium(dmpe) complexes (hundreds of turnovers)103 have recently been reported, but the scope of the reactions is limited to the specific type of alkene. 

Amino-6//-l,2,4-oxadiazin-3(2//)-ones (127) are accessible by regioselective amine attack at the thione carbon center of 5,6-dihydro-5-thioxo-2//-l,2,4-oxadiazin-3(477)-ones (126) (Equation... 

Alkoxyanthranilic acids have been prepared by regioselective amination of aryl oxazolines using diphenyl phosphorazidate (Scheme... 

A series of hydrolytically stable monophenyl phosphonates (177) has been synthesized and found to serve as irreversible and mechanism-based inhibitors of Escherichia coli and human y-glutamyl transpeptidase. Phosphonic add analogues of acylcarni-tyne (178) have been prepared in an optically active form expecting camityne palmitoyltransferase CPTI inhibitory activities. The synthetic methodology was based on catalytic asymmetric dihydroxylation of p,y-unsaturated phosphonates (179) and subsequent regioselective amination via cyclic sulfates (Scheme 60). ... 

Scheme 2.34 Ligand-controlled, Ag-catalyzed regioselective amination of C(sp )-H bond [195]...

Starting with a titanium-catalyzed regioselective amine addition, subsequent treatment with trimethylsilane cyanide provides the a-amino acid equivalent 30 [14],... 

Scheme 21 Sasaki s regioselective amination strategy in the synthesis of 4,6-diaminosugars.

Huertas, I., Gallardo, I., and Marquet, J., Direct formation of aromatic C-N bonds. Regioselective amination of m-dinitrobenzene via fluoride promoted nucleophilic aromatic photosubstitution for hydrogen. Tetrahedron Lett., 41, 279, 2000. 

Progress has been made toward enantioselective and highly regioselective Michael type alkylations of 2-cyclohexen-l -one using alkylcuprates with chiral auxiliary ligands, e. g., anions of either enantiomer of N-[2-(dimethylamino)ethyl]ephedrine (E. J. Corey, 1986), of (S)-2-(methoxymethyl)pyrrolidine (from L-proline R. K. EHeter, 1987) or of chiramt (= (R,R)-N-(l-phenylethyl)-7-[(l-phenylethyl)iinino]-l,3,5-cycloheptatrien-l-amine, a chiral aminotro-ponimine G. M. Villacorta, 1988). Enantioselectivities of up to 95% have been reported. 

There also exists an acidregioselective condensation of the aldol type, namely the Mannich reaction (B. Reichert, 1959 H. Hellmann, 1960 see also p. 291f.). The condensation of secondary amines with aldehydes yields Immonium salts, which react with ketones to give 3-amino ketones (=Mannich bases). Ketones with two enolizable CHj-groupings may form 1,5-diamino-3-pentanones, but monosubstitution products can always be obtained in high yield. Unsymmetrical ketones react preferentially at the most highly substituted carbon atom. Sterical hindrance can reverse this regioselectivity. Thermal elimination of amines leads to the a,)3-unsaturated ketone. Another efficient pathway to vinyl ketones starts with the addition of terminal alkynes to immonium salts. On mercury(ll) catalyzed hydration the product is converted to the Mannich base (H. Smith, 1964). 

Allylic acetoxy groups can be substituted by amines in the presence of Pd(0) catalysts. At substituted cyclohexene derivatives the diastereoselectivity depends largely on the structure of the palladium catalyst. Polymer-bound palladium often leads to amination at the same face as the aoetoxy leaving group with regioselective attack at the sterically less hindered site of the intermediate ri -allyl complex (B.M. Trost, 1978). 

Chlorohydrin 61 is formed by the nucleophilic addition to ethylene with PdCl2 and CuCl2[103,104]. Regioselective chlorohydroxylation of the allylic amine 62 is possible by the participation of the heteroatom to give chlorohydrin 63. Allylic sulfides behave similarly[105]. 

FMO calculations using the MNDO method and electron-density calculations were performed to establish which calculations are in agreement with the experimentally observed regioselectivity of the SnH amination of some nitronaphthyridines (see Section III,B). 

Also, the observed highly regioselective course in the SnFI substitutions in 2-R-3-nitro-l, 8-naphthyridines (R = FI, OFI, Cl, NFI2, OEt) with the anion of chloromethyl phenyl sulfone was explained by MNDO quantum-chemical calculations showing that, like in the aminations, the interaction of FIOMO of the nucleophile with LUMO of the nitronaphthyridines controls the regioselectivity (91JFIC1075). 

Nitrosofurazans provide a regioselective access to unsymmetrical azoxyfurazans. Thus, oxidative coupling of 3-nitroso-4-methylfurazan with amines... 

The relative ease of preparation of condensed thiazole derivatives is a consequence of facile thiazole ring closure, and therefore also benzothiazole amines with an amino group on the benzene ring (except for the weakly regioselective nitration of benzothiazoles) are very easily accessible and useful substrates for the Gould-Jacobs reaction. 

The increase in thermodynamic stability of 85 is achieved by easy ring opening (01H127). This knowledge allows one to control the regioselectivity of the oxidative amination of the 6-aryl-l,2,4-tiiazine 4-oxides 53, obtaining either (i) the 5-amino-1,2,4-triazine 4-oxides 56 in the reaction of 53 with amines at low temperature in the presence of the oxidant or (ii) the 3-amino-1,2,4-triazine 4-oxides 88, provided the reaction is carried out in two steps (addition and oxidation) at room temperature or higher. 

For the regioselectivity similar rules as for the ester pyrolysis do apply. With simple, alkylsubstituted amine oxides a statistical mixture of regioisomeric olefins is obtained. On the other hand with cycloalkyl amine oxides the regioselectivity is determined by the ability to pass through a planar, five-membered transition state. This has been demonstrated for the elimination reaction of menthyl dimethylamine oxide 10 and neomenthyl dimethylamine oxide 11 ... 

A regioselective synthesis of 2-amino[l, 2,4]triazinones 708 was reported (82JHC1583 83JHC1671) by reaction of 706 with 0-(2,4-dinitrophenyl)-hydroxylamine 707 as an amino transfer agent. Subsequent reaction of 708 with ammonia or amines, followed by ring closure with formic acid, provided 709. 

Entry Amine Regioselectivity (19 20) reaction method1 1 Product, yield (mp)[b ... 

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