Substitution reactions iridium-catalyzed alkylation

The most fundamental reaction is the alkylation of benzene with ethene.38,38a-38c Arylation of inactivated alkenes with inactivated arenes proceeds with the aid of a binuclear Ir(m) catalyst, [Ir(/x-acac-0,0,C3)(acac-0,0)(acac-C3)]2, to afford anti-Markovnikov hydroarylation products (Equation (33)). The iridium-catalyzed reaction of benzene with ethene at 180 °G for 3 h gives ethylbenzene (TN = 455, TOF = 0.0421 s 1). The reaction of benzene with propene leads to the formation of /z-propylbenzene and isopropylbenzene in 61% and 39% selectivities (TN = 13, TOF = 0.0110s-1). The catalytic reaction of the dinuclear Ir complex is shown to proceed via the formation of a mononuclear bis-acac-0,0 phenyl-Ir(m) species.388 The interesting aspect is the lack of /3-hydride elimination from the aryliridium intermediates giving the olefinic products. The reaction of substituted arenes with olefins provides a mixture of regioisomers. For example, the reaction of toluene with ethene affords m- and />-isomers in 63% and 37% selectivity, respectively. 

The first iridium catalysts for allylic substitution were published in 1997. Takeuchi showed that the combination of [fr(COD)Cl]2 and triphenylphosphite catalyzes the addition of malonate nucleophiles to the substituted terminus of t -allyliridium intermediates that are generated from allylic acetates. This selectivity for attack at the more substituted terminus gives rise to the branched allylic alkylation products (Fig. 4), rather than the linear products that had been formed by palladium-catalyzed allylic substitution reactions at that time [7]. The initial scope of iridium-catalyzed allylic substitution was also restricted to stabilized enolate nucleophiles, but it was quickly expanded to a wide range of other nucleophiles. 

The first enantioselective, iridium-catalyzed allylic substitution was reported by Helmchen and coworkers soon after the initial report by Takeuchi. Helmchen studied catalysts generated from phosphinooxazoline (PHOX) ligands and [Ir(COD)Cl]2 for the reactions of sodium dimethylmalonate with cinnamyl acetates (Scheme 2) [50]. The alkylation products were isolated in nearly quantitative yield and were formed with ratios of branched-to-Unear products up to 99 1 and with enantioselectivities up to 95% ee. In this and subsequent studies with PHOX ligands [51,52], Helmchen et al. demonstrated that the highest yields and selectivities were obtained with a PHOX ligand containing electron-withdrawing substituents and... 

Although Helmchen et al. showed that asymmetric iridium-catalyzed allylic substitution could be achieved, the scope of the reactions catalyzed by iridium complexes of the PHOX ligands was limited. Thus, they evaluated reactions catalyzed by complexes generated from [lr(COD)Cl]2 and the dimethylamine-derived phosphoramidite monophos (Scheme 8) [45,51]. Although selectivity for the branched isomer from addition of malonate nucleophiles to allylic acetates was excellent, the highest enantiomeric excess obtained was 86%. This enantiomeric excess was obtained from a reaction of racemic branched allylic acetate. The enantiomeric excess was lower when linear allylic acetates were used. This system catalyzed addition of the hthium salts of A-benzyl sulfonamides to aUylic acetates, but the product of the reaction between this reagent and an alkyl-substituted linear aUylic acetate was formed with an enantiomeric excess of 13%. 

The phosphoramidite ligands that are the focus of the remainder of this chapter have prompted the investigation of ligands containing related structures. Iridium complexes of aspartic acid-derived P-chirogenic diaminophosphine oxides (DlAPHOXs) catalyze the amination [62] and alkylation [63] of aUyhc carbonates (Scheme 6). With BSA as base and catalytic amounts of NaPFs as additive, branched amination and alkylation products were obtained from cinnamyl carbonates in excellent yields and enantioselectivities. However, the yields and enantios-electivities were lower for the reactions of alkyl-substituted aUyhc carbonates. Added LiOAc increased the enantioselectivities of aUyhc alkylation products. 

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