Additions amines, palladium chloride

Buchwald has shown that, in combination with palladium(II) acetate or Pd2(dba)3 [tris(dibenzylideneacetone)dipalladium], the Merrifield resin-bound electron-rich dialkylphosphinobiphenyl ligand (45) (Scheme 4.29) forms the active polymer-supported catalysts for amination and Suzuki reactions [121]. Inactivated aryl iodides, bromides, or even chlorides can be employed as substrates in these reactions. The catalyst derived from ligand (45) and a palladium source can be recycled for both amination and Suzuki reactions without addition of palladium. 

A palladium-catalyzed three-component reaction with 2-iodobenzoyl chloride or methyl 2-iodobenzoate, allene and primary aliphatic or aromatic amines to prepare fV-substituted 4-methylene-3,4-dihydro-1 (27/)-isoquinolin-1 -ones was disclosed <02TL2601>. A synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines via a Cp2TiMe2-catalyzed, intramolecular hydroamination/cyclization of aminoalkynes was also reported <02TL3715>. Additionally, a palladium-catalyzed one-atom ring expansion of methoxyl allenyl compounds 79 to prepare compounds 80 that can serve as precursors to isoquinolones was reported <02OL455,02SL480>. 

Others have investigated the kinetics of amination reactions mediated by catalyst systems employing the new electron-rich monodentate ligands. In particular, Hartwig has shown that for catalysis by a 1 1 palladium to Xn tert-butyl)phosphine system, a mechanism in which oxidative addition of aryl chlorides follows coordination of base to the palladium competes with the standard nonanionic pathway. Finally, Caddick, Cloke, and coworkers have studied amination reactions of aryl chlorides performed by palladium complexes of N-heterocyclic carbene ligands. They found the rate to be limited by the oxidative addition step, which occurs first through the dissociation of an NHC ligand. 

Simple terminal alkenes or tranx-disubstituted alkenes gave good yields of the formal addition product when three equivalents of a secondary amine (dimethyl- or diethyl-, but not diisopropylamine) and bis(benzonitrilc)palladium chloride were used at low temperature, after reduction of the C-Pd bond. The yields were modest to very low with (Z)- or cyclic alkenes and using primary amines9, l0. 

Compound la is prepared by reacting bis(benzonitrile)palladium chloride with butadiene in benzeneTHF or acetone - at RT. In methanol, the methoxy complex Ib is formed instead ", and in acetic acid the acetate Ic is produced . Additional examples of nucleophiles are sulfinates and amines. The E groups are readily displaced e.g., CH3O, acetate and (CH3)2N can be rapidly displaced in the presence of catalytic amounts of acid. 

The animation of aryl chlorides is desirable due to their prevalence and lower costs as compared to aryl bromides and iodides. Aryl chlorides are less prone to oxidative addition to palladium(O) and therefore require more activating ligands. An early example of ArCl amination was reported by M. Beller and co-workers.52 They found a palladacycle derived from Pd(OAc)2 and (o-tol)3P, for example, trawj-di(p-acetato)-bis[o-(di-o-tolylphosphino)benzyl]dipalladium(II). This catalyst allows for the amination of electron deficient aryl chlorides (13) with piperidine in the presence of catalytic LiBr and KO/-Bu as the stoichiometric base. The high temperature required (135 °C) also gives rise to a minor amount of the meta aminated product 15, likely due to aryne formation. It is unclear from this example whether a true oxidative addition to the aryl chloride is occurring, or whether the para product 14 also results from aryne formation, as a 1 1 mixture of products 14 and 15 also results without palladacycle present. 

Bulky phosphines, such as (/-Bu)3P, were shown to provide a palladium catalyst which is able to aminate and chlorides at room temperature with secondary amines of all type along with anilines.35,53,54,55 Primary amines give very low yields, except if coupling an o-tolyl aryl chloride. In addition, Hartwig has shown that NaOH may be used as a base under biphasic conditions (toluene/aq. NaOH) with a phase transfer catalyst (Ci6H33NMe3Br). 

Lewis, A.K.D., Caddick, S., Cloke, F.G.N. et al. (2003) Synthetic, structural, and mechanistic studies on the oxidative addition of aromatic chlorides to a palladium (N-heterocyclic carbene) complex relevance to catalytic amination. J.Am. Chem. Soc., 125, 10066-73. 

Subsequently, Green investigated the oxidahve addition of aryl chlorides to palladium complexes derived from NHCs and their role in catalytic aminations [206], by using density functional theory (DFT) methods. Here, the most likely transition-state model for oxidative addition is the monocarbene-palladium complex (NHC)Pd(ArCl). For the amination of chlorobenzene, coordination of the T-shaped oxidative addition product by the amine occurs with a rearrangement, placing the amine in a ds-position to the aryl group, a prerequisite for reductive elimination [2]. 

The mechanism of this process has been studied in detail. The identity of the palladium(O) species that lies on the catalytic cycle/ the effect of anions on the oxidative addition step/ " the effect of amines in the dissociation of chelating ligands from the palladium(O) complex during the oxidative addition/ the mechanism of formation of the amido complex/ and the mechanism of reductive elimination of amine - - have all been studied. The oxidative addition of aryl chlorides and bromides is generally the turnover-limiting step of the catalytic cycle. 

All substrates mentioned in the previous chapter easily undergo palladium-catalyzed aminocarbonylation also. It should be mentioned that even allylic carbonates instead of halides could be converted into carboxamides by this method, as it vas demonstrated during the total synthesis of antillatoxin [94]. The use of aryl chlorides is somewhat restricted owing to the low reactivity ofthese type of substrates in oxidative addition to palladium(O), as well as the competitive amination observed, for example, in the reaction of 1-chloroisoquinoline [95]. Functionalization of a great number of pharmaceutically important skeletons, for example, steroids [96-99], tropenes [100], benzodiazepines [101], indoles [102], benzo[c[quinolizine derivatives [103], and quinolones [104], have been carried out. 

Independently, Caddick et al. reported microwave-assisted amination of aryl chlorides using a palladium-N-heterocyclic carbene complex as the catalyst (Scheme 99) [lOlj. Initial experiments in a domestic microwave oven (reflux conditions) revealed that the solvent is crucial for the reaction. The Pd source also proved very important, since Pd(OAc)2 at high power in DMF gave extensive catalyst decomposition and using it at medium and low power gave no reaction at all. Pd(dba)2/imidazohum salt (1 mol% catalyst loading) in DME with the addition of some DMF was found to be suitable. Oil bath experiments indicated that only thermal effects are governing the amination reactions. 

The groups R2N and Cl can be added directly to alkenes, allenes, conjugated dienes, and alkynes, by treatment with dialkyl-V-chloroamines and acids. " These are free-radical additions, with initial attack by the R2NH- radical ion. " N-Halo amides (RCONHX) add RCONH and X to double bonds under the influence of UV light or chromous chloride. " Amines add to allenes in the presence of a palladium catalyst. ... 

Bei der Palladium(ll)-chlorid bzw. Palladiumkomplex-katalysierten Reaktion von Allen mit Ammoniak oder primaren Aminen erfolgt sowohl C,C-Verkniipfung von zwei Molekii-len Allen als auch Ammoniak- bzw. Amin-Addition. Das hierbei entstehende primare bzw. sekundare Amin kann seinerseits eine weitere Addition eingehen, so daB man ein Gcmisch von N-unsubstituiertem (im Fall von Ammoniak) bzw. N-Alkyl-substituiertem (im Fall von Alkylamin) 2-Aminomethyl-3-methyl-l,3-butadien und dem entsprcchenden Bis-[3-me-thyl-2-methylen-3-butenyl -amin erhalt, dessen Zusammensetzung von den Reaktionsbe-... 

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