Catalysts Crabtree

The stereochemistry of reduction by homogeneous catalysts is often controlled by functional groups in the reactant. Delivery of hydrogen occurs cis to a polar functional group. This behavior has been found to be particularly characteristic of an iridium-based catalyst that contains cyclooctadiene, pyridine, and tricyclohexylphosphine as ligands, known as the Crabtree catalyst 6 Homogeneous iridium catalysts have been found to be influenced not only by hydroxy groups, but also by amide, ester, and ether substituents.17... 

The Crabtree catalyst also exhibited superior stereoselectivity in comparison with other catalysts in reduction of an exocyclic methylene group.20... 

Another series of achiral iridium catalysts containing phosphine and heterocyclic carbenes have also been tested in the hydrogenation of unfunctionalized alkenes [38]. These showed similar activity to the Crabtree catalyst, with one analogue giving improved conversion in the hydrogenation of 11. 

The development of facial selective addition reactions of cyclohexa-1,4-dienes 7 and 14 has greatly extended the value of the asymmetric Birch reduction-alkylation. For example, amide directed hydrogenation of 15 with the Crabtree catalyst system occurs with outstanding facial selectivity iyw to the amide carbonyl group to give 16 (Scheme 5)."... 

Fig. 2 Comparison of Crabtree catalyst with the BArp analog...

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). 

A large number of reports have concerned transfer hydrogenation using isopropanol as donor, with imines, carbonyls-and occasionally alkenes-as substrate (Scheme 3.17). In some early studies conducted by Nolan and coworkers [36], NHC analogues of Crabtree catalysts, [Ir(cod)(py)(L)]PF,5 (L= Imes, Ipr, Icy) all proved to be active. The series of chelating iridium(III) carbene complexes shown in Scheme 3.5 (upper structure) proved to be accessible via a simple synthesis and catalytically active for hydrogen transfer from alcohols to ketones and imines. Unexpectedly, iridium was more active than the corresponding Rh complexes, but... 

The black solution containing IL and lr(0) nanoparticles (-2.0nm in diameter, as determined by TEM) can also be recycled in catalytic hydrogenation reactions. The catalytic activity of these soluble iridium nanoparticles was also compared to that of the Crabtree catalyst ([lr(COD)(PCy3)py]PF( ) in BMI-PFg. These nanoparticles maintain an efficient activity for at least seven recycles, whereas the Crabtree catalyst suffers a significant reduction in activity during recycling reactions. 

In Section 9-4-3, we mentioned that cationic Ir catalysts (sometimes called Crabtree catalysts) are quite active for hydrogenation of highly substituted C=C bonds. Moreover, asymmetric Ir-catalyzed hydrogenation of an imine is a key step in the industrial-scale synthesis of the herbicide (S)-metolachlor (Section 9-7-2). In addition to these applications, relatively recent work has shown that cationic Ir(I) complexes bonded to chiral ligands can catalyze asymmetric hydrogenation of unfunctionalized C=C bonds (i.e., C=C bonds to which no polar functional groups, such as C=0, are attached). 

The counterion as well was found to strongly influence catalyst performance. Initial experiments with Ir-PHOX complexes gave high enantioselectivity and full conversion, but only at high catalyst loadings of 4 mol% (Scheme 2b) [9]. Lower catalyst loadings resulted in decreased conversion due to catalyst deactivation [14] with concomitant formation of an inactive trinuclear iridium hydride cluster 8 (Scheme 4) [15], analogous to the deactivation products observed with the Crabtree catalyst 6 [16]. 

Crabtree Catalyst = [lr(PR3)2(K -02CC2F5)2H2] R = Cy or C6H4CF3 35 turnovers with acceptor 35 turnovers without acceptor in open reflux... 

Crabtree catalyst tris(cyclohexyl)phosphane [(1-2- DEAD diethyl azodicarboxylate... 

The great advantage of the Crabtree catalyst is that it is able to coordinate to Lewis basic groups in the substrate, thus directing the reduction to a specific face of the double bond. The diastereospecificity achieved is generally very high (Table 23.1), and such directed reductions have proved synthetically useful (Figure 23.30). 

TABLE 23.1 Directed Hydrogenation Using the Crabtree Catalyst... 

FIGURE 23.30 Applications of directed hydrogenation using the Crabtree catalyst. 

The Crabtree catalyst, [lr(PCy3)(py)(COD)][PFg], catalyzes the reduction of tri- and tetrasubstituted alkenes as well as less substituted ones. The reactions of aikenes bearing a potentially coordinating functionai group are highiy diastereoseiective. 

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