BIPHEP asymmetric hydrogenation

Using RuCl3/CK)-MeO-BIPHEP catalytic system, the /Uhydroxy ester, a key intermediate to vWF receptor antagonists Sulfobacin A, was produced through asymmetric hydrogenation in 96% yield and 99% ee (Scheme 8).266 The... 

BINAP system with excellent ee s. For example, 0// 0-bromoacetophenone can be converted into the corresponding chiral alcohol with 96% ee (Equation (72)). However, this type of substrate can be hydrogenated more effectively with the Ru/chiral phosphine/diamine system.279 Asymmetric hydrogenation of phenylthioketones has been realized with Ru catalysts. BINAP, MeO-BIPHEP,280 BDPP281 and Me-CnrPHOS,62c are efficient for this transformation (Table 17). 

Using Ir/MeO-Biphep/l2 catalyst system, a variety of substituted quinoline derivatives were hydrogenated in 95% yield and up to 96% ee. This method provided an efficient accesss to three naturally occurring alkaloids (Scheme 17).328 Ferrocene N, P ligand 108 is also effective for the asymmetric hydrogenation of quinolines with up to 92% ee.188a... 

Modification of the electronic and steric properties of BINAP, BIPHEMP, and MeO-BI-PHEP led to the development of new efficient atropisomeric ligands. Although most of them are efficient for ruthenium-catalyzed asymmetric hydrogenation [3], Zhang et al. have recently reported an ortho-substituted BIPHEP ligand, o-Ph-HexaMeO-BIPHEP, for the rhodium-catalyzed asymmetric hydrogenation of cyclic enamides (Scheme 1.2) [31]. 

This ligand, MeO-BIPHEP (96a), has shown similar reactivities and enantioselectivities to catalysts that contain BINAP.117 Ruthenium catalysts that contain MeO-BIPHEP have been used in several asymmetric hydrogenations from bench scale to multi-ton scale, which include the large-scale preparation of a P-keto ester, an aryl ketone, allylic alcohol, and several oc,P-unsaturated carboxylic acid substrates, which are shown in Figure 12.5. 

Bayer entered the asymmetric hydrogenation field with the development of a biphenyl ligand similar to MeO-Biphemp called Cl-MeO-biphemp (96b). This ligand has been prepared at kilogram scale by two procedures. One approach is an analogue of that used for MeO-Biphep (96a) (Scheme 12.30).121-124 The second method proceeds through a tricyclic intermediate (Scheme 12.32).122125... 

Scheme 15 illustrates the asymmetric hydrogenation of 3-keto phosphonates catalyzed by a BINAP-Ru complex, giving P-hydroxy phosphonates in up to 99% ee [61]. The sense of enantioface differentiation is the same as that of hydrogenation of P-keto carboxylic esters (see table of Scheme 3). The reactivity of the phosphonates is much higher than that of the carboxylic esters so that the hydrogenation proceeds even at 1 to 4 atm of hydrogen and at room temperature. A Ru complex of BDPP also shows high enantioselectivity [46b]. Chiral P-hydroxy phosphonates thus obtained are useful intermediates for the syntheses of phosphonic acid-based antibiotics as well as haptens of catalytic antibodies. Similarly, P-keto thiophosphates are hydrogenated enantioselectively with a MeO-BIPHEP-Ru catalyst [61b].

---