BisP* ligands

The success of Burk s alkyl diphosphines spurred development of a number of other ligands with electron rich phosphines, such as Zhang s PennPHOS (7) [36-38], Marinetti s /Pr-CnrPHOS (8) [39], and Imamoto s BisP ligands (9) [40],... 

Scheme 49 Enantiomerically pure (BisP ) ligands 161 and MT-Siliphos with bulky substituents...

The desired acids 31 were obtained by simply bubbling CO2 through a solution of the deprotonated phosphine boranes 4 and could be quantitatively reduced to (3-hydroxyphosphines 32. The hydroxyl group of 32 was then mesylated or tosylated in good yields to alford compounds 33, which were employed to prepare other compounds like P/N and P/S bidentate ligands (see later in this section) and unsymmetric BisP ligands (Section 5.2.1.3). The yields of compounds 31-33 are listed in Table 5.7. 

Another expansion of the BisP family was the preparation Ci-diphosphines with different alkyl groups on each phosphorus atom (unsymmetric BisP ligands), disclosed by Ohashi and Imamoto. " Unsymmetric BisP Kgands were prepared by coupling two of the precursors discussed in Section 5.2.1.1 the lithiated secondary phosphine boranes 9 and the mesylates or tosylates 33 (Scheme 5.32). 

The very good results of BisP ligands in several catalytic reactions prompted Yamanoi and Imamoto to simplify even further their structure but maintain... 

With this system two isomers can be formed 58 (endo) and 59 (exo). With the QUIPHOS ligand and copper catalysis, Buono and co-workers obtained very high endo/exo ratios and excellent conversion and enantioselectivity if the reagents were mixed at — 78 °C and slowly warmed to 25 °C. Imamoto and co-workers used the oxide, the 1-Ad-BisP ligand and iron catalysis at 0°C with modest results of diastereo- and enantioselectivity. Other BisP and MiniPHOS ligands led to inferior results. 

BisP ligands are highly active and enantioselective for the hydrogenation of many classes of substrates. As noted in the mechanistic discussion, studies on asymmetric hydrogenation by rhodium catalysts of terf-Bu-BisP have provided evidence that these reactions occur through the "hydrogen-first" pathway even though the complexes are cationic. ... 

The numerous chiral phosphine ligands which are available to date [21] can be subclassified into three major categories depending on the location of the chiral center ligands presenting axial chirality (e.g., BINAP 1 and MOP 2), those bearing a chiral carbon-backbone (e.g., DIOP 3, DuPHOS 4), and those bearing the chiral center at the phosphorus atom (e. g., DIPAMP 5, BisP 6), as depicted in Fig. 1. 

Although the asymmetric hydrogenation of itaconic acid derivatives is a potential synthetic approach to many useful product [105], lower enantioselectivities are often reported. In contrast with other catalysts, f-Bu-BisP, Ad-BisP, t-Bu-MiniPHOS, BIPNOR 27, and Brown s ligand 25 gave high to almost perfect ees in the hydrogenation of these substrates (Scheme 23) [101]. 

The Rh(I)-catalyzed asymmetric hydrogenation of dimethyl 1-benzoyloxy-ethenephosphonate 2 using f-Bu-BisP as the chiral ligand gave the corresponding (S)-product in 88% ee (Scheme 27) [120], enantioselectivity being comparable to those observed by Burk et al. [121]. 

The hydrogenation of />,/>-disubsti tilled a-dehydroamino acids remains a relatively challenging problem. The Rh complexes of chiral ligands such as Cy-BisP [58a], MiniPhos [65], and unsymmetrical BisP 13 [67b] have shown high efficiencies for some / ,/ -disubstituted a-dehydroamino acid substrates. Some efficient examples of hydrogenation of / ,/1-dimethyl a-dehydroamino acid esters with different chiral phosphorus ligands are listed in Table 26.2. 

S,S)-l,2-BIS(rERT-BUTYLMETHYLPHOSPHINO)ETHANE (BisP ) SYNTHESIS AND USE AS A LIGAND... 

A number of attempts have been made to find an accurate empirical predictor of the sense of product chirality. The twist in the diphosphine chelating ring is one example 8 twists lead to S product while X twists lead to R product [7, 49]. However, ligands such as DuPHOS have no backbone twist. Another predictor is the twist in the coordinated diene of the catalyst precursor catalysts with dienes twisted counterclockwise lead to R products, with clockwise leading to S [50], This works well for most ligands, but fails for BisP, which exhibits a small clockwise twist but produces R product... 

Figure 1.7. Catalytic hydrogenation of Al-acylated dehydroamino esters via dihydride/ unsaturate mechanism the p substituents in the substrates are omitted for clarity [P-P = (i ,i )-r-Bu-BisP S = solvent or a weak ligand].

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