Chiral compounds diphosphines

The hydrogenation of ketones with O or N functions in the a- or / -position is accomplished by several rhodium compounds [46 a, b, e, g, i, j, m, 56], Many of these examples have been applied in the synthesis of biologically active chiral products [59]. One of the first examples was the asymmetric synthesis of pantothenic acid, a member of the B complex vitamins and an important constituent of coenzyme A. Ojima et al. first described this synthesis in 1978, the most significant step being the enantioselective reduction of a cyclic a-keto ester, dihydro-4,4-dimethyl-2,3-furandione, to D-(-)-pantoyl lactone. A rhodium complex derived from [RhCl(COD)]2 and the chiral pyrrolidino diphosphine, (2S,4S)-N-tert-butoxy-carbonyl-4-diphenylphosphino-2-diphenylphosphinomethyl-pyrrolidine ((S, S) -... 

The enantioselective hydrogenation of prochirai heteroaromatics is of major relevance for the synthesis of biologically active compounds, some of which are difficult to access via stereoselective organic synthesis [4], This is the case for substituted N-heterocycles such as piperazines, pyridines, indoles, and quinoxa-lines. The hydrogenation of these substrates by supported metal particles generally leads to diastereoselective products [4], while molecular catalysts turn out to be more efficient in enantioselective processes. Rhodium and chiral chelating diphosphines constitute the ingredients of the vast majority of the known molecular catalysts. 

The mechanism of the enantioselective 1,4-addition of Grignard reagents to a,j3-unsaturated carbonyl compounds promoted by copper complexes of chiral ferrocenyl diphosphines has been explored through kinetic, spectroscopic, and electrochemical analysis.86 On the basis of these studies, a structure of the active catalyst is proposed. The roles of the solvent, copper halide, and the Grignard reagent have been examined. 

Equation 12.31 shows an example of enantioselective displacement (desymme-trization) by azide ion of one of the two methyl carbonate ligands of meso compound 24 to yield 25 in 82% yield with >95% ee.63 This was accomplished using a Pd complex also bound to chiral diamide-diphosphine ligand (26).64 Other Trost ligands include structures 27 and 28. 

Enantioselective intramolecular cyclization of secondary phosphines 216 or their boranes, catalyzed by chiral palladium(diphosphine) complexes, afforded P-stereogenic benzophospholanes 217 with moderate stereoselectivity (59-70% ee) and yields. However, the absolute configuration of compounds has not been established. This reaction allowed chiral phospholanes to be obtained, which are valuable ligands in asymmetric catalysis (Scheme 70) [115]. 

Many chiral ferrocenyl diphosphines (Fig. 45) are effective for the rhodium-, iridium-, or ruthenium-catalyzed hydrogenation of dehydroamino acids and related compounds, as well as imines (145,166-172). 

On the other hand, the enantioselective 1,4-addition of carbanions such as enolates to linear enones is an interesting challenge, since relatively few efficient methods exist for these transformations. The Michael reaction of p-dicarbonyl compounds with a,p-unsaturated ketones can be catalysed by a number of transition-metal compounds. The asymmetric version of this reaction has been performed using chiral diol, diamine, and diphosphine ligands. In the past few years, bidentate and polydentate thioethers have begun to be considered as chiral ligands for this reaction. As an example, Christoffers et al. have developed the synthesis of several S/O-bidentate and S/O/S-tridentate thioether... 

Fig. 32.28 Examples of bioactive compounds and chiral diphosphines obtainable by BlNAP-Ru-catalyzed hydrogenation via dynamic kinetic resolution.

The most common chiral auxiliaries are diphosphines (biphep, binap and analogues, DuPhos, ferrocenyl-based ligands, etc.) and cinchona and tartaric acid-derived compounds. It is clear that the optimal chiral auxiliary is determined not only by the chiral backbone (type or family) but also by the substituents of the coordinating groups. Therefore, modular ligands with substituents that can easily be varied and tuned to the needs of a specific transformation have an inherent advantage (principle of modularity). 

In summary, the asymmetric hydrogenation of olefins or functionalized ketones catalysed by chiral transition metal complexes is one of the most practical methods for preparing optically active organic compounds. Ruthenium and rhodium-diphosphine complexes, using molecular hydrogen or hydrogen transfer, are the most common catalysts in this area. The hydrogenation of simple ketones has proved to be difficult with metallic catalysts. However,... 

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