Asymmetric direct hydrogenation

Ligand design elements in precious metal homogeneous catalysts for asymmetric direct hydrogenation and asymmetric transfer hydrogenation... 

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. ... 

In entry 15 of Table 21.10, it is noted that even a remote hydroxyl group directed hydrogenation by the cationic [Rh(diphos-4)(nbd)]+ catalyst to afford a moderate diastereoselectivity (80 20) [23]. This is an interesting example of long-range 1,5-asymmetric induction. 

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)."... 

The pyrrolobenzodiazepine-5,11 -diones II have been utilized in asymmetric syntheses of both the cis- and tra i-decahydro-quinoline alkaloids (Schemes 21 and 22). For example, reduction of 100 with 4.4 equiv. of potassium in the presence of 2 equiv. of t-BuOH, followed by protonation of the resulting enolate with NH4CI at —78 °C gave the cA-fused tetra-hydrobenzene derivative 101.Amide-directed hydrogenation of 101 gave the hexahydrobenzene derivative with diastereo-selectivity greater than 99 1. Removal of the chiral auxiliary and adjustment of the oxidation state provided aldehyde 103 which was efficiently converted to the poison frog alkaloid (+)-pumiliotoxin C. 

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). 

In spite of the success of asymmetric iridium catalysts for the direct hydrogenation of alkenes, there has been very limited research into the use of alternative hydrogen donors. Carreira and coworkers have reported an enantioselective reduction of nitroalkenes in water using formic acid and the iridium aqua complex 69 [66]. For example, the reduction of nitroalkene 70 led to the formation of the product 71 in good yield and enantioselectivity (Scheme 17). The use of other aryl substrates afforded similar levels of enantioselectivity. 

The mixture of 40a and 40b was directly converted to the corresponding acetonide 41 (Scheme 8). Then, the asymmetric transfer hydrogenation was performed following Noyori s procedure.28 The... 

The asymmetric catalytic hydrogenation of 4-aryl coumarins has been reported (Scheme 30) <1999TL3293>. Initial attempts to asymmetrically hydrogenate coumarin 240 directly proved unsuccessful. However, upon lactone opening, 241 was smoothly converted to hydrogenated product 242, which would relactonize to 243 gradually on standing or more quickly under catalysis with />-toluenesulfonic acid. 

The side-on (r)2) bonding in M r 2-H2 and other a-complexes has been termed non-classical, on analogy to the 3-center, 2-electron bonding in non-classical carbocations and boranes (Fig. 2). One of the first questions raised when H2 complexes were discovered is whether they would be important in catalytic reactions. As will be shown below the answer is an emphatic yes, as exemplified by the elegant asymmetric catalytic hydrogenation systems of Nobel-laureate Ryoji Noyori. Also, the mechanism of catalytic silane alcoholysis directly involves two different a complexes M(r 2-Si-H) and M(r 2-H2). In both of these systems, the crucial step is heterolytic cleavage of the H H and/or Si-H bond, the primary subject of this review. 

Applications in Total Synthesis. Two recent examples of directed hydrogenations employing (1) in the total synthesis of complex molecules are illustrated. In eq I a simultaneous diastereoselective reduction of the trisuhstituted alkene and the a,p-unsaturated ester afforded the illustrated advanced intermediate in the asymmetric total synthesis of ionomycin. In addition, a two-directional application has been utilized in an asymmetric synthesis FK-506 (eq 2). ... 

Chiral Amines with a Disubstituted Nitrogen Atom, HNR R 183 Table 6.1 Metals used in catalysts for direct asymmetric imine hydrogenation. 

Unlike most rhodium homogeneous catalysts, the ruthenium(BlNAP) series is very effective for the asymmetric hydrogenation of functional ketones48. This leads to a number of experimental circumstances where the directing effect of substituents is brought into play. One of the most commonly used examples of asymmetric ketone hydrogenation is that of /1-keto esters. Diketone reduction with ruthenium[(5)-BINAP] demonstrates the high enantiomeric purity due to double asymmetric induction. 

Following the development of successful catalytic hydrogenation of olefins, recent attention is directed to catalytic hydrogenation and transfer hydrogenation of ketones and imines [77]. Because of requirement of production of various pharmaceutical compounds of importance, further development is expected in asymmetric catalytic hydrogenation. 

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