Direct iridium-catalyzed

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

Virtually every iridium catalyst of the formula [Ir(L )(COD)] [X] for asymmetric olefin hydrogenation that has appeared after the initial counterion effect studies was based on BArp as the preferred anion [14]. The anion effect is broadly applicable in iridium-catalyzed reductions as experiments with a direct analog of the Crabtree catalyst of the formula [Ir(pyridine)(Cy3P)(COD)]BArp indicates (Fig. 2). 

The mechanism for the iridium-catalyzed hydrogen transfer reaction between alcohols and ketones has been investigated, and there are three main reaction pathways that have been proposed (Scheme 4). Pathway (a) involves a direct hydrogen transfer where hydride transfer takes place between the alkoxide and ketone, which is simultaneously coordinated to the iridium center. Computational studies have given support to this mechanism for some iridium catalysts [18]. 

A diverse group of secondary and tertiary amines are readily synthesized from the reaction of primary and secondary amines with allylic carbonates in the presence of preformed iridium metalacycles, but the direct synthesis of primary amines via iridium-catalyzed allylic amination requires the use of ammonia as a nucleophile. The asymmetric allylation of ammonia had not been reported until very recently, and it is not a common reagent in other metal-catalyzed reactions. Nonetheless, Hartwig and coworkers developed the reactions of ammonia with allylic carbonates in the presence of la generated in situ [89]. Reactions conducted in the initial work led exclusively to the products from diallylation (Scheme 16). Further advances in... 

These recent mechanistic studies have provided the foundation for the most recent work that has expanded the scope of iridium-catalyzed allylic substitution. The synthesis and characterization of the ethylene-bound complex lb resulted directly... 

The use of ethylene adduct lb is particularly important when the species added to activate catalyst la is incompatible with one of the reaction components. Iridium-catalyzed monoallylation of ammonia requires high concentrations of ammonia, but these conditions are not compatible with the additive [Ir(COD)Cl]2 because this complex reacts with ammonia [102]. Thus, a reaction between ammonia and ethyl ciimamyl carbonate catalyzed by ethylene adduct lb produces the monoallylation product in higher yield than the same reaction catalyzed by la and [Ir(COD)Cl]2 (Scheme 27). Ammonia reacts with a range of allylic carbonates in the presence of lb to form branched primary allylic amines in good yield and high enantioselectivity (Scheme 28). Quenching these reactions with acyl chlorides or anhydrides leads to a one-pot synthesis of branched allylic amides that are not yet directly accessible by metal-catalyzed allylation of amides. 

Iridium-catalyzed borylation has also proved to develop the first general approach to functionalized unprotected indoles at the 7-position [67]. This selectivity can be explained by the nitrogen-directed aromatic borylation pathway in the mechanistic steps (Scheme 7.34). 

A convenient direct route has recently been described for obtaining regioregular polyalkylthiophenes using a tandem iridium-catalyzed borylation to produce the monomer, and a palladium-mediated coupling to produce the polymer [68]. The treatment of substituted thiophenes with B2pin2 in the presence of [lrCl2(COD)]2/ 4,4 -di-tert-butyl-2,2 -bipyridine (DTBPY) provided the expected monomer in 97% yield (Scheme 7.35). 

Iridium-Catalyzed Direct Arylation of Aromatic C—H Bonds... 

Alternative synthetic approaches include enantioselective addition of the organometallic reagent to quinoline in the first step of the synthesis [16], the resolution of the racemic amines resulting from simple protonation of anions 1 (Scheme 2.1.5.1, Method C) by diastereomeric salts formation [17] or by enzymatic kinetic resolution [18], and the iridium-catalyzed enantioselective hydrogenation of 2-substituted quinolines [19]. All these methodologies would avoid the need for diastereomer separation later on, and give direct access to enantio-enriched QUINAPHOS derivatives bearing achiral or tropoisomeric diols. Current work in our laboratories is directed to the evaluation of these methods. 

Although early reports suggested that iridium complexes were ineffective catalysts for the hydroboration reaction, subsequent work has shown that Crabtree s catalyst (see Crabtree s Catalyst), [Ir(cod)(py)(PCy3)] PFe, can be used for ether or amide-directed hydroborations. For instance, iridium catalyzed hydroborations of pyrrolidinyl amides with HBcat gave syn 1,3-hydroxyl amides with high levels of regio- and stereocontrol (equation 5). In contrast, reactions... 

Scheme 9.30 Iridium-catalyzed direct arylations of benzene (87) and toluene (90).

Iridium-catalyzed hydrogenations of olefins and ketmies have also been reported. These reactions have not yet been studied computationally at the level of detail of the rhodium- and ruthenium-catalyzed reactions, and comparisons to experiments have been less clear. As a result, only a very general description of the mechanism and rationalization of the stereoselective outcome is available at this time. The results do, however, clearly demonstrates that amidst such mechanistic diversity of the iridium- and the ruthenium-catalyzed reactions, they prefer either the direct transfer after migratory insertion, or the concerted transfer. 

Scheme 9.39 Iridium-catalyzed direct arylation of anisole (29).

Lu Y, Kim IS, Hassan A, Del Valle DJ, Krische MJ (2009) 1, n-Glycols as dialdehyde equivalents in iridium-catalyzed enantioselective carbonyl allylation and iterative two-directional assembly of 1,3-polyols. Angew Chem Int Ed 48 5018-5021... 

As already mentioned, the C-H/C-X coupling between simple arenes and aryl halides to form biphenyl derivatives is difficult in terms of reactivity and regiose-lectivity without directing group. In 2004, Fujita and Yamaguchi [28] reported the iridium-catalyzed direct arylation of benzene with aryl iodides. For example, when the reaction was carried out in the presence of the [Cp IrHCl]2 catalyst (5mol%) and KOt-Bu (3.3 equiv.) at 80°C, 4-methoxybiphenyl 34 was obtained in 66% yield. However, when substituted arenes were used instead of benzene, several... 

Catellani [61] reported a palladium/norbomene-catalyzed synthesis of heteroatom-containing o-teraryls from aryl iodides and heteroarenes (including indoles and pyrroles) through double C-H arylation. Fagnou s group [62] applied their own protocol (Pd(II)/Ag(I)/carboxylic acid) to achieve the direct arylation of azaindoles. Itami [63] demonstrated the first iridium-catalyzed C-H arylation of heteroarenes (involving indoles and pyrroles) with aryl halides. 

As one might expect from its inherent reactivity for the metallation of indole, the selective iridium-catalyzed monoborylation of indole at the C2 position proceeded efficiently to afford the corresponding boronate ester in 92% yield. A later report outlined the C7-borylation of indole in systems where the C2 position had been blocked with an alkyl or ester substituent. The need for a C2 substituent to achieve exclusive C7 borylation was obviated when a landmark report from the Hartwig laboratory detailed that indoles 92 could undergo C7-borylation when a silyl-directed... 

Can the iridium chemistry tolerate substrates with primary alcohols Need to generate an aryltrifluoroborate salt Yes, a version of the iridium-catalyzed C—H borylation is tolerant to the presence of primary alcohols [75] A convenient precursor for the direct synthesis is not readily available. Try generating an arylboronic acid or arylboronate, and treat it with a solution of KHP [37, 38]. For arylboronates, a 4 1 THF/water mixture was successful [38]... 

The attainment of optimum rate at relatively low [H2O] is a significant benefit for the iridium system, since it results in less costly product purification. A typical configuration for an iridium-catalyzed methanol carbonylation plant is shown in Figure 2. The feedstocks (MeOH and CO) are fed to the reactor vessel on a continuous basis. In the initial product separation step, the reaction mixture is passed from the reactor into a flash tank where the pressure is reduced to induce vaporization of most of the volatiles. The catalyst remains dissolved in the liquid phase and is recycled back to the reactor vessel. The vapor from the flash tank is directed into a distillation train, which removes methyl iodide, water, and heavier byproducts (e.g., propionic acid) from the acetic acid product. At the relatively high water levels used in the rhodium-catalyzed Monsanto process, three distillation columns are typically required. In the Cativa process, a lower water concentration means that the necessary product purification can be achieved with only two columns. 

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