Iridium based racemization catalyst

Scientists at Huddersfield University in collaboration with Avecia have developed a DKR process involving the combination of immobilized Candida rugosa lipase and an iridium-based racemization catalyst (Scheme 2.30). By using carbonate 62 as the acyl donor, the racemic secondary amine 61 was converted to the corresponding carbamate (R)-63 in high yield and enantiomeric excess [32]. 

While very fruitfully results can be accomplished in the resolution of primary amines, not many examples have been reported for the resolution of secondary amines. It is worthy of mention that the racemization of secondary amines was successfully achieved by the employment of a novel iridium-based racemization catalyst. In this sense. Page and coworkers reported the pentamethylcyclopentadienyl iridium(III) iodide dimer [IrCp I jj, which is very active for the racemization of secondary amines under mild conditions (Figure 14.26) and completely compatible with enzyme-catalyzed KR in a DKR process [109,110]. 

Based on the concept mentioned above, Brown realized the asymmetric deactivation of a racemic catalyst in asymmetric hydrogenation (Scheme 9.18) [35]. One enantiomer of (+)-CHIRAPHOS 28 was selectively converted into an inactive complex 30 with a chiral iridium complex 29, whereas the remaining enantiomer of CHIRAPHOS forms a chiral rhodium complex 31 that acts as the chiral catalyst for the enantioselective hydrogenation of dehydroamino acid derivative 32 to give an enantio-enriched phenylalanine derivative... 

As described earlier, Pd and Ru catalysts were useful for the DKR of primary amines. However, they, were not effective for the DKR of secondary amines. The Page group introduced an iridium complex, [IrCpIjlj, as the racemization catalyst for the DKR of secondary amines [56]. They accomplished the DKR of an isoquinoline-based secondary amine with [IrCpy j, C. rugosa lipase (CRL), and 3-methoxyphenyl propyl carbonate as tiie acyl donor (SAeme 5.33). 

Notably, at DSM a technically feasible process technology based on this type of DKR has been developed [5, 23]. In the presence of modified and more simplified ruthenium or iridium catalysts, respectively, for racemization in combination with the lipase from C. antarctica B, the DKR was conducted using racemic phenylethan-l-ol as a substrate, leading to the desired O-acylated product with 97% and 99% yield, respectively, and excellent (>99%) ee [5, 23]. 

All methyl isomers of norbornene, 1-, 2-, 5-, and 7-methylnorbornene have been reacted in the presence of catalysts based on tungsten, rhenium, ruthenium, osmium and iridium compounds [7]. The polymers corresponded to ring-opened products having various microstructures. Racemic mixtures or pure enantiomers have been used as starting materials. Differences in reactivities as a function of the methyl position (1, 2, 5 or 7) and steric configuration (endo-exo and syn-anti) have been reported. 

The synthesis of chiral racemic atropisomeric pyridines by cobalt-catalyzed [2 + 2 + 2] cycloaddition between diynes and nitriles was reported in 2006 by Hrdina et al. using standard CpCo catalysts [CpCo(CO)2, CpCo(C2H4)2, CpCo(COD)] [34], On the other hand, chiral complexes of type II were used by Gutnov et al. in 2004 [35] and by Hapke et al. in 2010 [36] for the synthesis of enantiomerically enriched atropisomers of 2-arylpyridines (Scheme 1.18). This topic is described in detail in Chapter 9. It is noteworthy that the 2004 paper contains the first examples of asymmetric cobalt-catalyzed [2 - - 2 - - 2] cycloadditions. At that time, it had been preceded by only three articles dealing with asymmetric nickel-catalyzed transformations [37]. Then enantioselective metal-catalyzed [2 -i- 2 - - 2] cycloadditions gained popularity, mostly with iridium- and rhodium-based catalysts, as shown in Chapter 9. 

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