Heck reaction amino

Transition metal-catalyzed intramolecular cyclization has also been applied to the formation of imidazoles. Palladium-mediated amino Heck reactions of 0-pentafluorobenzoylamidoximes 1163 afford l-benzyl-4-methylimid-azoles 1164 with a range of substituents at the 2-position. This method is particularly suitable for the preparation of imidazoles with a chiral substituent at the 2-position (Scheme 283) <20050L609>. 

Scheme 164. Carbon-Heteroatom Bond Formation by (a) Coupling with a Heteroatom, (b) Amino-Heck Reaction, (c) Insertion of C-C Unsaturated Bonds-Coupling with Heteroatoms, and (d) Sonogashira Coupling of Terminal Alkynes Followed by Cyclization...

The amino-Heck reaction, which proceeded through N—O bond cleavage of oxime derivatives, has been... 

An N-0 bond in oxime derivatives undergoes oxidative addition to form a Pd-imino bond. New Pd-catalyzed reaetions of oximes, such as the amino Heck reaction, have been discovered (see Chapter 3.2.10) [34]. 

Microwave-assisted Heck reaction of (hetero)aryl bromides with N,N-dimethyl-2-[(2-phenylvinyl)oxy]ethanamine, using Herrmann s palladacycle as a precatalyst, yielded the corresponding /3-(hetero)arylated Heck products in a good EjZ selectivity (Scheme 79) [90]. The a/yd-regioselectivity can be explained by the chelation control in the insertion step. This selectivity is better than 10/90 when no severe steric hindrance is introduced in the (hetero)aryl bromides. The process does not require an inert atmosphere. There is evidence that a Pd(0)/Pd(II)- and not Pd(II)/Pd(IV)-based catalytic cycle is involved. Similarly, other j6-amino-substituted vinyl ethers such as... 

Methyl-l,2,3,9-tetrahydro-4H-carbazol-4-one, the key building block of the neuroactive compound alosetron, was easily obtained from 3-[(2-halophenyl)(methyl)amino]cyclohex-2-en-l-one by pyrrole ring formation via Heck reaction under microwave irradiation [94], While the iodo substrate gave an excellent yield in only 30 min at 100 °C the corresponding bromo derivative converted only poorly under the same reaction conditions (Scheme 88). 

Palladium metal catalysts supported on organic resins containing tertiary amino, cyano, carboxyl, and pyridyl groups have been recently investigated in some Heck reactions, such as the coupling of iodobenzene with methyl acrylate and methyl vinyl ether (Scheme 11) [31]. 

The Heck reaction has proven to be an extremely useful method for the formation of C-C bond at a vinyl carbon centre. There are numerous reported examples of enantioselctive Pd catalyzed C-C bond forming reactions.10"13 Surprisingly, reports of Heck transformations using amino acid based phosphine, phosphinite ligands are rare. Recently Gilbertson reported a proline derived phosphine-oxozoline ligand in a catalytic asymmetric Heck reaction.5 In this paper we present some novel amino acids derived ligands as part of a catalytic system for use in asymmetric Heck reactions. 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(Af-rerf-butoxycarbonyl-lV-methyl)amino-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5-yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261], Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

Heck reactions have also been used by Helmchen et al. for a two-component domino process of a,co-amino-1,3-dienes.1721 By using palladium complexes with chiral phosphino-oxazolines as catalysts an enantiomeric excess of up to 80 % is achieved. In a... 

Intramolecular aminopalladation has been applied to the total synthesis of the complex skeleton of bukittinggine (179). For this reaction. Pd(CF3CO )2 (10 mol%) and benzoquinone (1.1 equiv.) are used. It is important to use freshly recrystallized benzoquinone for successful cyclization. Formation of a 7r-allylpalladium species as an intermediate in this amination reaction has been suggested 182]. The amino group in obromoaniline reacts first with acrylate in the presence of PdCF to give 180, and then intramolecular Heck reaction of the resulting alkene 180 with Pd(0) catalyst affords indolecarboxylate 181[183]. 

Polystyrene-bound secondary aliphatic amines and /V-alkyl amino acids can be ally-lated by treatment with a diene and an aryl iodide or bromide in the presence of palla-dium(II) acetate (Entry 14, Table 10.3). As the diene, 1,3-, 1,4-, and 1,5-dienes can be used, and, besides aryl halides, heteroaryl bromides have also been successfully used [63], This remarkable reaction is likely to proceed via the formation of an aryl palladium complex, with subsequent insertion of an alkene into the C-Pd bond. The resulting organopalladium compound does not undergo ( -elimination (as in the Heck reaction), but isomerizes to an allyl palladium complex, which reacts with the amine to give the observed allyl amines. 

The intramolecular Heck reaction (type d cyclization) has been used to access 3-benzazepine derivatives from o-bromobenzyl substituted /3-amino ester precursors in excellent yields. A key feature though was the use of microwave irradiation in the poly(ethylene glycol), PEG3400, as the solvent <2007EJ0201>. 

Iyer, S. Ramesh, C. Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts for the Heck reaction. Tetrahedron Lett. 2000, 41, 8981-8984. 

A range of imines and enamines, formed from tir/Zw-haloaminopyridines and ketones, may be converted to a variety of substituted 4-, 5-, 6-, and 7-azaindoles by microwave-assisted intramolecular Heck reaction <2005S2571>. As an example, 4-amino-3-iodopyridine is converted to azaindole 85 in 46% yield by condensation with ketone 86 followed by Heck reaction of the resulting enamine (Equation 59). 

With chiral ligands the Heck reaction can be enantioselective. The amino-acid-derived phosphin ligand in the margin controls the Heck reaction of phenyl triflate with dihydrofnran. The ligan. selects one enantio topic face of the alkene (see Chapter 45 if you have forgotten this term) and th usual douhle hond migration and (3 elimination complete the reaction. 

Optically pure ligands on Pd in allylic alkylation can give good enantiomeric excess. You have already seen the first chiral amino-phosphine as the ligand in a chiral Heck reaction and it also gives excellent results in this example. It has to be said, however, that this is a very well behaved example and the next one is more impressive. 

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