Hydrogenation Reactions - Carbohydrates: Tools for Stereoselective Synthesis - page 170

Ph 2 P (OMe) 5

Ph 2 P

(MeO) 7 (OMe) 7

59

Figure 8.10

Cyclodextrin containing diphosphines ( 59 ).

positions 6 of a -cyclodextrin. The Rh/ 59 catalytic system has been tested in the

hydrogenation of substrates 1a-d and 3a,b (Scheme 8.1), affording up to 92% ee,
but only organic solvents were used for these reactions [35].
Several types of mixed carbohydrate ligands have been developed for application
in asymmetric hydrogenation catalysis. In particular, phosphine-phosphite and
phosphite-phosphoroamidite ligands have produced excellent results [3a].
Phosphine-phosphites 60a-d derived from xylose were used as ligands in the
Rh-catalyzed asymmetric hydrogenation of several

β

α , β -unsaturated carboxylic acid

derivatives (up to 99% ee) under very mild reaction conditions (Figure 8.11) [36].

Scheme 8.8 shows the synthesis of ligands 60. The variation of the biphenyl sub-
stituents in the phosphite moiety greatly affected the enantioselectivity. The best
enantioselectivity was obtained using ligand 60b, which contains bulky tert -butyl
groups in the ortho and para positions of the biphenyl moiety. The results also
indicate that the sense of stereoinduction is mainly controlled by the configuration
of the axially chiral phosphite moiety. Both enantiomers can therefore be obtained
with high enantioselectivities. Notably, these phosphite-phosphine ligands showed
higher degrees of enantioselectivity and higher reaction rates than their corre-
sponding diphosphine ( 56 ) and diphosphite ( 29 ) analogues under the same reac-
tion conditions. 31 P-{ 1 H} NMR and kinetic studies on intermediates of the catalytic
cycle show that the [Rh(P-P

>

phosphite-phosphine) species
is the resting state and that the rate dependence is first order in rhodium and
hydrogen pressure and zero order in enamide concentration [37].

′ )(enamide)]BF 4 (P-P ′ =

P(OR) 2

Ph 2 P Ph 2 P

OH O

O

(a) (b)

O

O O

O O O O

O O

60

Scheme 8.8 Synthesis ligands 60: (a) KPPh 2 /DMF (80% yield); (b) (OR) 2 PCl/Py/toluene
(45-71% yield).

Phosphinite-phosphite ligands 61e,f modified with different substituents
(Figure 8.11) have shown considerable activity and selectivity together with higher
ee than the related diphosphite ligands. When the catalytic precursor [Ir(COD) 2 ]