Amines iridium catalyst

Asymmetric hydrogenation of nitrones in an iridium catalyst system, prepared from [IrCl(cod)]2, (S)-BINAP, NBu 4 BH4, gives with high enantioselectivity the corresponding A-hydroxylamines which are important biologically active compounds and precursors of amines (480). Further reduction of hydroxylamines to secondary amines or imines can be realized upon treatment with Fe/AcOH (479), or anhydrous titanium trichloride in tetrahydrofuran (THF) at room temperature (481). 

The most widely used iridium catalyst for the V-alkylation of amines with alcohols is [Cp lrCl2]2, which was identified and developed by Fujita, Yamaguchi, and CO workers [94]. Aniline 111 has been selectively alkylated by a range of... 

A wide range of carbon, nitrogen, and oxygen nucleophiles react with allylic esters in the presence of iridium catalysts to form branched allylic substitution products. The bulk of the recent literature on iridium-catalyzed allylic substitution has focused on catalysts derived from [Ir(COD)Cl]2 and phosphoramidite ligands. These complexes catalyze the formation of enantiomerically enriched allylic amines, allylic ethers, and (3-branched y-8 unsaturated carbonyl compounds. The latest generation and most commonly used of these catalysts (Scheme 1) consists of a cyclometalated iridium-phosphoramidite core chelated by 1,5-cyclooctadiene. A fifth coordination site is occupied in catalyst precursors by an additional -phosphoramidite or ethylene. The phosphoramidite that is used to generate the metalacyclic core typically contains one BlNOLate and one bis-arylethylamino group on phosphorus. 

Reactions of allylic electrophiles with stabilized carbon nucleophiles were shown by Helmchen and coworkers to occur in the presence of iridium-phosphoramidite catalysts containing LI (Scheme 10) [66,69], but alkylations of linear allylic acetates with salts of dimethylmalonate occurred with variable yield, branched-to-linear selectivity, and enantioselectivity. Although selectivities were improved by the addition of lithium chloride, enantioselectivities still ranged from 82-94%, and branched selectivities from 55-91%. Reactions catalyzed by complexes of phosphoramidite ligands derived from primary amines resulted in the formation of alkylation products with higher branched-to-linear ratios but lower enantioselectivities. These selectivities were improved by the development of metalacyclic iridium catalysts discussed in the next section and salt-free reaction conditions described later in this chapter. 

Scheme 2.30 DKR of secondary amine 61 using a novel iridium catalyst.

Screening several amine racemization catalysts, we found that the SCRAM and the Shvo catalyst would both racemize the (S)-enantiomer at temperatures above 11() G. Interestingly, no dimeric products were found. The best racemization conditions were found to be using toluene or TBME at 150°C in a pressure vessel with 1 mol% SCRAM or 5 mol% Shvo catalyst over 24 h, providing quantitative conversion. In the presence of (R, R)-dibenzoyltartaric acid the racemization slowed, possibly because of unfavorable coordination of the alkylammonium substrate or acid quenching of the iridium hydride catalyst intermediate. 

An iridium catalyst (52) has been found to catalyse H-D exchange in a variety of unsaturated carboxylic acids, ketones and amines.155 The mechanism presumably involves displacement of cyclooctadiene by a solvent molecule, which later on is replaced by the a,p-unsaturated compound. 

Allylic amination of 70 using iridium catalyst has also been reported recently using a chiral phophoramidite ligand. The reaction produced the branched product 72 over the linear monoalkylated and dialkylated products and the amines... 

An interesting variation of hydroformylation with a great potential for the industrial preparation of primary amines is hydroaminomethylation. In this process two catalytic reactions are combined, a hydroformylation and a reductive amination of the resulting aldehyde. Although first described more than 60 years ago a really successful procedure was only published recently [78]. To ensure the success of this sequence a rhodium catalyst for the hydroformylation was combined with an iridium catalyst for the imine reduction in a two-phase system, similar to the Ruhrchemie/Rhone-Poulenc process for the hydroformylation. It was demonstrated that less polar solvents such as toluene in combina-... 

Z)-Enynols can also be employed as substrates when ruthenium or iridium catalysts are used <2006ASC1671>. Furan-2-acetic esters are obtained by a Pd(n)-catalyzed oxidative cyclization-alkoxycarbonylation of (Z)-enynols <1999JOC7693>. In analogy, 2-furan-2-ylacetamides are obtained in an aminocarbonylation with secondary amines (Equation 22) <2006S4247>. 

Amination of benzylic alcohol using a mixed NHC/phosphane iridium catalyst. 

Iridium catalysts generally favour chiral branched products in contrast to palladium catalysts, which typically give rise to linear achiral products. The catalyst system [Ir(COD)Cl]2-P(OPh)3 is effective in allylic alkylation and amination h... 

Selective reduction to hydroxylamine can be achieved in a variety of ways the most widely applicable systems utilize zinc and ammonium chloride in an aqueous or alcoholic medium. The overreduction to amines can be prevented by using a two-phase solvent system. Hydroxylamines have also been obtained from nitro compounds using molecular hydrogen and iridium catalysts. A rapid metal-catalyzed transfer reduction of aromatic nitroarenes to N-substituted hydroxylamines has also been developed the method employs palladium and rhodium on charcoal as catalyst and a variety of hydrogen donors such as cyclohexene, hydrazine, formic acid and phosphinic acid. The reduction of nitroarenes to arylhydroxyl-amines can also be achieved using hydrazine in the presence of Raney nickel or iron(III) oxide. ... 

Pfaltz systems represent promising beginnings for the asymmetric hydrogenation of enamines by discrete, cationic iridium catalysts, but both require more development before they can find wide use in amine synthesis. In particular, these systems are still highly substrate dependent, meaning that a new catalyst screening is necessary for each new substrate. 

Similarly, an iridium catalyst with a specific ferrocenylphosphine ligand (Scheme 2) is used in the production of the chiral amine (5)-metolachlor, a herbicide, by the asymmetric direct hydrogenation of a prochiral imine. ... 

The hydrogenation of C=N double bonds is an important synthetic strategy for the synthesis of secondary amines. Chiral iridium catalysts allow the hydrogenation of prochiral imines to be carried out with high enantioselectivity in conventional liquid solvents. Such a process has already found industrial application in the preparation of (S)-metolaclor, a herbicide produced by Novartis in Switzerland [40]. Recent research at the Max Planck Institute for Coal Research has demonstrated that reactions of this type can be carried out in SCCO2 with the same level of enantioselectivity and with enhanced catalyst efficiency [12]. 

The use of enantiomerically pure iridium catalysts allows the enantioselective allylic amination of linear substrates and this has been achieved with high ee using the iridium complex of phosphoramidite (10.84) and both acyclic and cyclic amines, including pyrrolidine and piperidine. ... 

The mechanism of this hydrogenation has not been revealed in detail, but several aspects are noteworthy in the context of the mechanistic discussion earlier in this chapter. First, this reaction almost certainly occurs by the insertion of an imine into a metal hydride (see Chapter 9), rather than by the transfer of a hydride and a proton by a metal-ligand bifunctional system. This iridium catalyst does not contain a protic ligand. Second, acid and iodide are needed as promoters to obtain the fast rates. The iodide is thought to help stabilize an iridium(III) species and the acid is thought to help in the release of the amine product from the metal. 

Complexes of ruthenium and rhodium have been identified that catalyze the hydrogenation of nitriles under mild conditions with very good selectivities to the primary amine. In particular, Otsuka and co-workers showed that [RhHfP Prj) ] catalyzes the hydrogenation of a variety of nitriles to amines under mild conditions (1 atm pressure, 20 °C, 2 h Equation 15.119). The reaction is reversible primary amines undergo dehydrogenation in the presence of [Rl iHfP Prj) ] to form nitriles (Equation 15.120). Iridium catalysts for the dehydrogenation of nitriles have also been reported recently. ... 

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