A. Solladie´-Ca6allo et al. / Tetrahedron Letters 42 (2001) 4741–4744
4743
Table 2. Hydrogenation of acid 5 and ester 8: Pd/Al2O3,
Of course, a satisfying modifier must not poison the H2
catalyst and it is worth noting that CD happens to
poison the palladium catalyst more than the platinum
catalyst. The last requirement for a good modifier will
be, of course, to have ‘enough’ chirality to induce high
enantiomeric excess.
H2 (40 bar), 24 h
Conditionsa
5
8
Conv. (%) ee (%) Conv. (%)
ee (%)
Without CD
100
0
–
–
100
0
–
–
5×10−3 equiv. CD:
Acknowledgements
A
5×10−3 equiv. CD:
30
21
10
0
B
The authors are grateful to Region Alsace and CNRS
for a grant to C.M. (BDI).
a [5]=[8]=0.3 M. Ester or acid/CD=100. Ester or acid/catalyst=
100.
References
indicates that CD strongly poisons the Pd catalyst while
it does not activate the substrate. The energy of the
double-bond p-electrons in salt 6 is only slightly
modified compared to the starting acid 5, as is the
energy of the p-electrons of complex 9 compared to 8.16
However, some conversion (30%) is obtained when a
mixture of 5 and CD is made before addition of the
catalyst (method B): that is when the salt 6 is formed
(as already proposed8,17) and prevents the free CD from
totally poisoning the catalyst.
1. Orito, Y.; Imai, S.; Niwa, S.; Nguyen, G. H. Synth. Org.
Chem. Jpn. 1979, 37, 173.
2. Lipkin, D.; Stewart, T. D. J. Am. Chem. Soc. 1939, 61,
3295.
3. For reviews, see: (a) Izumi, Y. Adv. Catal. 1983, 32, 215;
(b) Blaser, H. U. Tetrahedron: Asymmetry 1991, 2, 843;
(c) Baiker, A. J. Mol. Catal. 1997, 115, 473; (d) Wells, P.
B.; Wilkinson, A. G. Top. Catal. 1998, 5, 39; (e) Baiker,
A. J. Mol. Catal. 2000, 163, 205.
4. (a) Simons, K. E.; Wang, G.; Heinz, T.; Giger, T.;
Mallat, T.; Pfaltz, A.; Baiker, A. Tetrahedron: Asymmetry
1995, 6, 505; (b) Minder, B.; Schu¨rch, M.; Mallat, T.;
Baiker, A.; Heintz, T.; Pfaltz, A. J. Catal. 1996, 160, 261;
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Am. Chem. Soc. 2000, 122, 12675.
A conversion of 10% is obtained in the case of the ester
8 when the ester is mixed with CD before addition of
the catalyst supporting the presence of a weak associa-
tion (through an OH···OꢀC bond between the CD’s OH
and the carbonyl of ester 8) as already proposed18
which only partly prevents CD from poisoning the
catalyst. That CD strongly poisons palladium is consis-
tent with the observed decrease in the rate of hydro-
genation of pyruvate with Pd/Al2O3.7
6. (a) Blaser, H. U.; Jalett, H. P.; Monti, D. M.; Reber, J.
F.; Wehrli, J. T. Stud. Surf. Sci. Catal. 1988, 41, 153; (b)
Garland, M.; Blaser, H. U. J. Am. Chem. Soc. 1990, 112,
7048.
In conclusion, it is reasonable to envisage that, in the
case of Pt/hydrogenation of pyruvate, the modifier
(CD) is a substrate–catalyst (through formation of the
more reactive enol form), accelerates the reaction and
poisons only slightly the Pt/catalyst. The possible pres-
ence of ee is a consequence of formation of the
modifier/enol complex and of the chirality of the
modifier.
7. Hall, T. J.; Johnston, P.; Vermeer, W. A. H.; Watson, S.
R.; Wells, P. B. Stud. Surf. Sci. Catal. 1996, 101, 221.
8. Kun, I.; To¨ro¨k, B.; Felfo¨ldi, K.; Bartok, M. Appl. Catal.
A 2000, 203, 71.
9. Gertosio, V.; Santini, C. C.; Basset, J. M.; Bayard, F.;
Buendia, J.; Vivat, M. J. Mol. Catal. 1999, 142, 141.
10. Marcilly, C.; Franck, J. P. Revue de l’IFP 1984, 39,
337–364.
11. The CD-OH group is not considered for anchoring of
enolate to CD because it has been shown that replace-
ment of the OH by OMe or OAc does not change the
reactivity nor the % ee. See: Blaser, H. U.; Jalett, H. P.;
Lottenbach, W.; Studer, M. J. Am. Chem. Soc. 2000, 122,
12675.
12. Because of enolization, the carbonyl of pyruvate esters
can only undergo reduction, hydrogenation and addition
of phenyl or vinyl Grignards.
In the case of Pd/hydrogenation of a,b-unsaturated
acid/ester, the modifier (CD) does not activate the
substrate but provides the chirality and slows down the
reaction by poisoning the Pd/catalyst.
For the design of new modifiers it should be kept in
mind that to activate enolizable ketoesters (pyruvate
and others) and accelerate the hydrogenation in aprotic
solvents, the modifier should have a pKa suitable to
provide enough enol and then to liberate the corre-
sponding hydroxy-ester once hydrogenation is over.20
From the above reasoning, it can also be deducted that
acceleration of hydrogenation of a,b-unsaturated acids-
(esters), which would imply modification of the energy
level of the CꢀC/p-electrons through association with
another molecule, will be most difficult.
13. Ferri, D.; Bu¨rgi, T.; Borszeky, K.; Mallat, T.; Baiker, A.
J. Catal. 2000, 193, 139.
14. Bonello, J. M.; Lambert, R. M.; Ku¨nzle, N.; Baiker, A. J.
Am. Chem. Soc. 2000, 122, 9864.
15. (a) Calculations have been carried out using PM3 on a
CAChe WorkSystem; (b) Partasarathy, R.; Ohrt, J.;
Horeau, A.; Vigneron, J. P.; Kagan, H. Tetrahedron
1970, 26, 4705.