Oxidative addition amine isomerization

The addition of a carbonylation step extended a pyrrole synthesis to pyrrole-2-acetic acid derivatives <06ASC2212>. Treatment of enyne amine 1 with palladium diiodide in the presence of CO and methanol produced pyrrole-2-acetic ester 2 via a 5-exo-dig cyclization, oxidative carbonylation, and isomerization. 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

Ab Initio MO calculations of a model complex Rh(PH3)2(NH3)(CH2=CHCH2NH2) were earned out to shed light to the detailed mechanism of Rh(l)-catalyzed isomerization of allylic amines to enamines.5 This study suggests that the square-planar [RhiPHjyNHjXCf CHCHjNHj) complex is transformed to [Rh(PH3)2(NH3)(( )-CH3CH=CHNH2)]+ via intramolecular oxidative addition of the C(l)-H bond to the Rh(I) center, giving a distorted-octahedral Rh(lll) hydride intermediate, followed by reductive elimination accompanied by allylic transposition. 

See [6]. The following reaction types have been listed (a) Geometric isomerization of alkenes (b) Allylic [1,3] hydrogen shift (c) Cycloaddition of alkenes. Dimerization, Tri-merization. Polymerization (d) Skeletal rearrangments of alkenes and methathesis (e) Hydrogenation of alkenes (f) Additions to alkenes (g) Additions to C = X (h) Aliphatic substitutions (i) Aromatic substitution (j) Vinyl substitution (k) Oxidation of alkenes (1) Oxidation of alcohols (m) Oxidation of arenes (n) Oxidative decarboxylation (o) Oxidation of amines (p) Oxidation of vinylsilanes and sulfides (q) Oxidation of benzal-dehyde (r) Dehydrogenations. 

A wide variety of nucleophiles add to an -rf-allyl ligand. Desirable nucleophiles typically include stabilized carbanions such as CH(COOR)2 or 1° and II0 amines. Unstabilized nucleophiles such as MeMgBr or MeLi often attack the metal first and then combine with the n-allyl by reductive elimination. The Tsuji-Trost reaction, which is typified by the addition of stabilized carbanions to T 3—allyl ligands complexed to palladium followed by loss of the resulting substituted alk-ene, comprises an extremely useful method of constructing new C-C bonds, and many applications of this reaction have appeared in the literature.61 Equation 8.43 illustrates an example of a Pd-catalyzed addition of a stabilized enolate to an allyl acetate.62 The initial step in the catalytic cycle is oxidative addition of the allyl acetate to the Pd(0) complex, followed by nq1 to nq3—allyl isomerization, and then attack by the nucleophile to a terminal position of the T 3—allyl ligand. We will discuss the Tsuji-Trost reaction, especially in regard to its utility in chiral synthesis,63 more extensively in Chapter 12. 

The pioneering studies in this area were reported in 1999 by Narasaka, who demonstrated intramolecular heteroatom Heck-type reactions of 0-pentafluorobenzoyl oximes [97]. As shown below, treatment of unsaturated substrate 97 with a catalytic amount of Pd(PPh,y in the presence of triethyl amine provided pyrrole 98 upon workup with chlorotrimethylsilane. The mechanism of this reaction proceeds via oxidative addition of the N—O bond to afford 99, which undergoes alkene insertion into the Pd—N bond to provide alkyl-palladium complex 100. The exo-methylene product 101 is generated by [i-hydride elimination from 100, and isomerization to the desired pyrrole 98 occurs when chlorotrimethylsilane is added. 

Studies on the origin of die regioselectivity of these reactions revealed that attack by amines occurred at the more-substituted position, but isomerization of the kinetic branched product to the thermodynamic linear product occurred faster than the catalytic process. As a result, the linear isomer was observed as the final reaction product. However, isomerization of the products formed by reactions of aziridines, hydroxylamines, and hydrazone deriviatives was slower than the catalytic substitution process, and these different relative rates allowed isolation of the branched substitution products. The isomerization process presumably occurs by protonation of the amine to form an ammonium salt that undergoes oxidative addition to palladium, as was observed in the initial allyUc substitution processes that involved allylic ammonium salts as electrophile. Thus, addition of a strong, non-nucleophihc base to the reactions of amine nucleophiles allowed isolation of the branched kinetic product. ... 

Isomerization of 3-cephems (27) to 2-cephems (28) takes place in the presence of organic bases (e.g. pyridine) and is most facile when the carboxyl is esterified. Normally an equilibrium mixture of 3 7 (3-cephem/2-cephem) is reached. Since the 2-cephem isomers are not active as antibacterial agents, the rearrangement proved to be an undesirable side reaction that complicated acylation of the C-7 amine under certain conditions. A method for converting such mixtures to the desired 3-cephem isomer involves oxidation with concomitant rearrangement to the 3-cephem sulfoxide followed by reduction. Additions... 

Bromocriptine is rapidly and completely metabolised in animals and man. The major components of the urinary metabolites have been identified as 2-bromo-lysergic acid and 2-bro-mo-isolysergic acid. Apart from the hydrolytic cleavage of the amine bond and the isomerization at position 8 of the lysergic acid moiety, a third principal biotransformation pathway consists in the oxidative attack of the molecule at the proline fragment of the peptide part, predominantly at position 8, giving rise to the formation of a number of hydroxylated and further oxidized derivatives of bromocriptine, and in addition of conjugated derivatives thereof. 

Hosokawa, Murahashi, and coworkers demonstrated the ability of Pd" to catalyze the oxidative conjugate addition of amide and carbamate nucleophiles to electron-deficient alkenes (Eq. 42) [177]. Approximately 10 years later, Stahl and coworkers discovered that Pd-catalyzed oxidative amination of styrene proceeds with either Markovnikov or anti-Markovnikov regioselectivity. The preferred isomer is dictated by the presence or absence of a Bronsted base (e.g., triethylamine or acetate), respectively (Scheme 12) [178,179]. Both of these reaction classes employ O2 as the stoichiometric oxidant, but optimal conditions include a copper cocatalyst. More recently, Stahl and coworkers found that the oxidative amination of unactivated alkyl olefins proceeds most effectively in the absence of a copper cocatalyst (Eq. 43) [180]. In the presence of 5mol% CUCI2, significant alkene amination is observed, but the product consists of a complicated isomeric mixture arising from migration of the double bond into thermodynamically more stable internal positions. 

Despite many attempts it has not been possible to oxidize 2-substituted 1,2,3-triazoles 382 to the corresponding 1-oxides 326. Peracetic acid, 3-chloroperbenzoic acid, dichloropermaleic acid, trifluoroperacetic acid, peroxydisulfuric acid, and f-pentyl hydrogen peroxide in the presence of molybdenum pentachloride all failed to oxidize 382 (1981JCS(P1)503). Alkylation of 1-hydroxytriazoles 443 invariantly produced the isomeric 3-substituted 1,2,3-triazole 1-oxides 448 (see Scheme 132). However, the 2-substituted 1,2,3-triazole 1-oxides 326 can be prepared by oxidative cyclization of 2-hydroxyiminohydrazones (1,2-hydrazonooximes, a-hydrazonooximes) 345 or by cyclization of azoxyoximes 169. Additional methods of more limited scope are reaction of nitroisoxazoles 353 with aryl-diazonium ion and base, and reaction of nitroimidazoles 355 with hydroxy-amine- or amine-induced rearrangement of nitro-substituted furoxanes 357. 

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