Phosphates asymmetric hydrogenation

Chirality transfer in catalytic asymmetric hydrogenation can be achieved not only by using powerful chiral ligands such as BINAP or DuPhos but also by the formation of a dynamic conformational isomer. The availability of many enantiomerically pure diols allows the production of electron-deficient, bi-dentate phosphate in the form of 27. The backbone O-R -O can define the chirality of the 0-R2-0 in complex 28, hence realizing the chirality transfer.44... 

For example, a wide range of a-(acyloxy)acrylates have been hydrogenated with excellent enantioselectivity using the Et-DuPhos-Rh catalyst. High selectivities are also obtained for the asymmetric hydrogenation of the B/Z-isomeric mixtures of yS-substituted derivatives (Eq. 12). Asymmetric hydrogenation of enol phosphates with either Du-Phos-Rh or BPE-Rh catalyst provides moderate to excellent enantioselectivity (Eq. 13)... 

Figure 8.12 U rea functionalized phosphate ligands for asymmetric hydrogenation of dimethyl itaconate (DMI), N-(3,4-dihydronaphthalen-2-yl)acetamide (DNA) and methyl 2-acetamidoacrylate (MAA).

SCHEME 29.6. Asymmetric hydrogenation in the s3mthesis of sitagliptin phosphate. 

Figure 7.4 The edges of the base pairs in DNA that ate in the major groove are wider than those in the minor groove, due to the asymmetric-attachment of the base pairs to the sugar-phosphate backbone (a). These edges contain different hydrogen bond donors and acceptors for potentially specific interactions with proteins (b).

In 2007, AntiUa and coworkers disclosed the first asymmetric organocatalytic reduction of acyclic a-imino esters (Scheme 23) [39], Chiral VAPOL phosphate (5)-16 (5 mol%) served as a catalyst for the transfer hydrogenation of the latter (62) employing commercially available dihydropyridine 44a to give both aromatic and aliphatic a-amino esters 63 in very high yields (85-98%) and enantioselectivities (94-99% ee). 

Herein, we report an extension of this methodology and report the metal-free hydrogenation of quinolines using 1 mol % of diphenyl phosphate (DPP) and the asymmetric variant of this procedure using 1 mol % of a chiral BlNOL-phosphate 1 as catalyst (Figure 4.2). 

For asymmetric hydrocarbohydroxylation, an efficient catalyst system consisting of PdCl2, CuCl2, and (7 )-l,l -binaphthyl-2,2 -diyl hydrogen phosphate, (7 )-(-)-BNPPA (51) was intro-... 

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