Ligand synthesis amination reactions

Phosphine ligands based on the ferrocene backbone are very efficient in many palladium-catalyzed reactions, e.g., cross-coupling reactions,248 Heck reaction,249 amination reaction,250 and enantioselective synthesis.251 A particularly interesting example of an unusual coordination mode of the l,l -bis(diphenylphosphino)ferrocene (dppf) ligand has been reported. Dicationic palladium(II) complexes, such as [(dppf)Pd(PPh3)]2+[BF4 ]2, were shown to contain a palladium-iron bond.252,253 Palladium-iron bonds occur also in monocationic methyl and acylpalladium(II) complexes.254 A palladium-iron interaction is favored by bulky alkyl substituents on phosphorus and a lower electron density at palladium. 

Abstract Several bismuth-catalyzed synthetic reactions, which proceed well in aqueous media, are discussed. Due to increasing demand of water as a solvent in organic synthesis, catalysts that can be used in aqueous media are becoming more and more important. Although bismuth Lewis acids are not very stable in water, it has been revealed that they can be stabilized by basic ligands. Chiral amine and related basic ligands combined with bismuth Lewis acids are particularly useful in asymmetric catalysis in aqueous media. On the other hand, bismuth hydroxide is stable and works as an efficient catalyst for carbon-carbon bond-forming reactions in water. 

As mentioned above, reactions of this type have been widely used in the synthesis of macrocyclic ligands. Indeed, some of the earliest examples of templated ligand synthesis involve thiolate alkylations. Many of the most important uses of metal thiolate complexes in these syntheses utilise the reduced nucleophilicity of a co-ordinated thiolate ligand. The lower reactivity results in increased selectivity and more controllable reactions. This is exemplified in the formation of an A -donor ligand by the condensation of biacetyl with the nickel(n) complex of 2-aminoethanethiol (Fig. 5-78). The electrophilic carbonyl reacts specifically with the co-ordinated amine, to give a complex of a new diimine ligand. The beauty of this reaction is that the free ligand cannot be prepared in a metal-free reac-... 

In oxidation reactions, however, osmium is significantly more selective than catalysts derived from other transition metals. Osmium-based catalysts for the hydroxylation and amination of aUcenes are very widely used in organic synthesis. With alkaloid-derived ligands, the hydroxylation and amination reactions are highly enantioselective (see Enantioselectivity). The use of bleach, hydrogen peroxide, ferric cyanide, and oxygen have been reported as secondary oxidants for some of these reactions. 

The amino alcohol-dialkylzinc system can be applied to ehiral amine synthesis. Polymer-supported ephedrine was found to be an effective chiral ligand in the reaction of N-diphenylphosphinoylimines with diethylzinc (Eq. 19) [77-79]. The polymeric catalysts were, however, less efficient than monomeric model reactions. Several dendrimeric chiral ligands containing the ephedrine moiety (60, 61) have also been synthesized and used in the asymmetric alkylation of 7 -diphenylphosphinylimines by diethylzinc [80]. Both yield and enantioselectivity of the reaction were, however, lower when the dendrimeric ligands were used. 

Nitrogen-containing phosphines (Figure 15) remain in the center of ligand synthesis. One reason for this may be in the solubility of the (unprotonated) amines in common organic solvents which allows the use of the methods of conventional organic synthesis. An additional aspect is in that amines can be further functionalized by several ways, for example as seen in 2.6 above. Another example is the reaction of 160 (diam-BINAP) with 2,6-tolylene diisocyanate affording an enantiopure polymeric... 

Transition metal catalyzed processes are useful tools for the synthesis of functionalized thiophenes. Thus for instance, a phosphine-free, palladium catalyzed coupling protocol for the synthesis of 2-arylbenzo[d]thiophenes from various 3-substituted benzo[6]thiophenes and aryl bromides or iodides has been reported <04T3221>. Likewise, 2,2 -bithiophenes have been 5,5 -diarylated directly with aryl bromides in the presence of Pd(OAc)2, bulky phosphine ligands and CS2CO3 <04T6757>. A series of electron-deficient and relatively electron-rich benzo[6]thienyl bromides have been shown to participate in palladium catalyzed amination reactions, as exemplified by the interesting conversion of 63 to the tetracyclic system 64 upon reaction with 2-aminopyridine 65 <04EJO3679>. 

Other efficient catalysts for the aryl amination reaction include the (NHC)-Pd(allyl)Cl series that bear the same metal/ligand ratio of 1 1 and allow excellent conversions to products at temperatures as low as room temperature [78]. Alkoxide bases lacking p-hydrogens (amylates and terf-butoxide) have a dual action in this system as they activate the catalyst through nucleophilic attack on the palladium allyl moiety and act as an efficient base for the catalytic process. The complexes were successfully used in the key step of a Cryptocarya alkaloid synthesis [79]. 

Very few examples of C2-lithiation reactions involving V-aryUndoles are known [258]. In the search for new indolyl phosphine ligands (e.g., 72) for palladium-catalyzed amination reactions, mono-lithiation and di-lithiation reactions involving V-arylindoles have been used (Scheme 15). Beller reported the synthesis of indolyl ligand 72a using a mono-lithiation of V-phenylindole (71a) [277], whereas Nifant ev used a dilithiation of 71b under much colder conditions to give bis (phosphine)indole 72b [278]. 

Enanliopure tetrahydrobenzo-l,4-diazepin-3-(3//)-one 42 was obtained by intramolecular amination of the aryl iodide 41 using BINAP as a ligand without racemization [36], The chiral imidazole 47 was prepared by successive Pd-catalyzed amination of the chiral amine 43 with 1,2-dibromobenzene to give 44, which was iminated with benzophenone imine (45). Then deprotection gave 46, and acid-catalyzed ring closure yielded 47 [37], The reactions have been applied to the synthesis of various chiral imidazolium salts as precursors of chiral carbene ligands [38]. Amination of aryl bromides proceeds very rapidly by temperature-controlled microwave heating [39]. 

The Buchwald-Hartwig amination reaction can facilitate the synthesis of nitrogen-containing heterocycles. For instance, Buchwald demonstrated that the amination reaction could be used to prepare N-arylhydrazones from hydrazones and aryl halides. Acid-catalyzed condensation of the hydrazone with a ketone then yielded the desired indoles.Hartwig described a similar arylhydrazone formation with DPPF as a ligand and CS2CO3 as a base."... 

Reactions of ammonia and amines with C = C double and C = C triple bonds are interesting because they allow the preparation of many valuable compounds [see Section 6.A.11.C and reactions (13.91) and (13.92)]. For example, the addition of ammonia to unsaturated acids would allow the preparation of amino acids. Application of catalysts with asymmetric ligands for this reaction could lead to synthesis of optically active amino acids, which already exist in nature. 

Although iminium cations are usually formed from a secondary amine and an aldehyde, other masked species can also be used in synthesis. Recently, Alper and co-workers reported the synthesis of hexahydropyrrolo[2,l,-6]oxazoles by the Rh-catalyzed hydroformylation of an oxazolidine heterocycle 164 (Scheme 76) with linear selective ligand Xanthphos. This reaction proceeds diastereoselectively through a unique and imexpected silica-mediated (Lewis Acid) hydroformylation-deformylation pathway (139). 

Fig. 5 Synthesis of end-functionalized PEO-PDLLA block copolymer (A) and conjugation of ligand molecule to the distal end of PEO via reductive amination reaction (B)...

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