Amine regioselectivity

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

Methylthio-1,2,4-triazin-5(2H)-ones are aminated regioselectively with 0-(2,4-dinitrophenyl)-hydroxylamine to give 2-amino-3-methylthio-l,2,4-triazin-5(2H)-ones (81) (82JHC1583, 83JHC1671). 

Methylthio-l,2,4-triazin-5(2//)-ones (194) can be aminated regioselectively with 0-(2,4-dinitrophenyl)hydroxylamine as an amino-transfer reagent to give 2-amino-3-methylthio-1,2,4-triazin-5(2//)-ones (195) (Scheme 38). Reaction of the products (195) with amines followed by ring closure with aliphatic acids provided [l,2,4]triazolo[2,3-6][l,2,4]triazin-7(l//)-ones (196) <82JHC1583, 83JHC1671>. 

Primary Amine Regioselectivity Pd Source Additive Overall Yield (%) ee (%) ... 

Compared to the hydroamination of alkynes, the protocols for more readily available olefins were rather limited. Ackermann presented a TiCU-catalyzed hydroamination reaction of norbornene using a variety of functionalized amines. Regioselective hydroarylation occurs as a competing reaction and the chemose-lectivity for hydroamination products ranges from poor to excellent [312]. This protocol can also be utilized in the hydroamination of vinylarenes with some electron-deficient amines [313] and the hydroamination of enyne compound. In the latter reaction, a subsequent rearrangement gives rise to a tetrahydroisoquinoline derivative (Scheme 14.134). 

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. 

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