Enantioselective hydrogenation of γꢀketoesters
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 10, October, 2005
2377
(30 m × 0.2 mm × 0.25 µm quartz capillary column, 2,6ꢀdiꢀ
pentylꢀ3ꢀ(trifluoroacetyl)ꢀβꢀcyclodextrin as the stationary phase,
a column temperature of 130 °C). Retention times/min: CH4
(nonꢀsorbable component), 3.5; 1b, 6.5; (R)ꢀ3, 12; (S)ꢀ3, 15.3.
The absolute configuration of the lactone was determined on the
basis of the known [α]D value for the predominant enantiomer.22
The sign of the optical rotation was determined on a PUꢀ09
spectropolarimeter (State Research Center for Scientific Instruꢀ
ment Making at the Bauman Moscow State Technical Uniꢀ
versity).
monohydride complex, [HRu(P*P)Cl], coordinates a
γꢀketoester molecule to give intermediate complex A. In
the presence of HCl, complex A is in equilibrium with
complex B, in which protonation of the keto group faciliꢀ
tates the subsequent hydride transfer giving rise to hydroxy
ester and to coordinatively unsaturated complex C, which
returns to the catalytic cycle. Apparently, due to the small
amounts and low concentrations of both complex A and
HCl, the A
B equilibrium in the absence of excess
Asymmetric catalytic hydrogenation (general procedure).
A. The BINAP ligand (12 mg, 0.019 mmol) and Ru(COD)(MA)2
(6 mg, 0.019 mmol) were placed in a glass tube for hydrogenaꢀ
tion, the tube was three times evacuated and filled with argon.
A 2 M solution of HCl in MeOH (19 µL, 0.038 mmol) was added
to anhydrous acetone (2 mL) and the resulting solution was
degassed through three cycles including liquid nitrogen freezing,
evacuation, thawing, and argon filling and then injected into the
hydrogenation tube containing the ligand and the ruthenium
complex. The mixture was stirred for 0.5 h; during this period, a
yellowꢀ or orangeꢀcolored precipitate was formed. After evapoꢀ
ration of acetone in vacuo, a solution of ketoester 1b (519 mg,
3.6 mmol) in a mixture of EtOH (2 mL) and 2 M HCl in MeOH
(95 µL, 0.19 mmol), preꢀdegassed three times, was added to the
residual solid complex. Then the tube was placed into a stainꢀ
lessꢀsteel autoclave (50 mL) preꢀfilled with argon, the autoclave
was purged with purified hydrogen, and the H2 pressure was
adjusted to 60—70 atm. The reaction mixture was magnetically
stirred. After completion of the experiment, the reaction mixꢀ
ture was passed through a 1 cmꢀthick silica gel layer (elution
with hexane—ethyl acetate, 9 : 1) to separate the catalyst. The
solvent was evaporated at 40 °C on a rotary evaporator, and the
residue was analyzed by NMR and GLC.
HCl is substantially shifted to the left. In this case, an
increase in the medium acidity would shift this equilibꢀ
rium toward the formation of complex B and, as a conseꢀ
quence, increase the hydrogenation rate. The heterolysis
of the η2ꢀcoordinated hydrogen molecule and hydrogeꢀ
nation of the acidꢀactivated keto group can take place
synchronously in the coordination sphere of ruthenium
complex D, which is equilibrated with the reaction
complex B. The formation of intermediates of types B
and D has been assumed previously16,17 for analogous
RuIIꢀcatalyzed hydrogenation of 1,3ꢀdicarbonyl comꢀ
pounds.
In addition to the foregoing, the coordinatively unꢀ
saturated complex C involved in the catalytic cycle is in
equilibrium in solution with its lowꢀactivity linear or ring
associates18,19 containing Ru...Cl bridging bonds. An inꢀ
crease in the degree of the acidꢀcatalyzed dissociation of
these associates can induce an additional acceleration of
hydrogenation.
Thus, of the catalytic systems tested, the Ruꢀ1 system
([HCl]/[Ru] = 10) exhibited the highest activity accomꢀ
panied by a high enantioselectivity in the asymmetric
hydrogenation of γꢀketoesters derived from levulinic acid.
Currently, we are investigating other γꢀketoesters as subꢀ
strates in order to develop a convenient general method
for the preparation of enaniomerically pure γꢀalkylꢀ
γꢀbutyrolactones.
B. The BINAP ligand (12 mg, 0.019 mmol) and
Ru(COD)(MA)2 (6 mg, 0.019 mmol) were placed into a glass
tube for hydrogenation, three times evacuated and filled with
argon, and a preꢀdegassed solution of ketoester 1b (519 mg,
3.6 mmol) in EtOH (2 mL) and 2 M HCl in MeOH (95 µL,
0.19 mmol) were added. Further operations were as described in
procedure A.
References
Experimental
Commercial levulinic acid (Acros) was used. Ethyl and isoꢀ
propyl levulinates were prepared by a standard procedure and
tertꢀbutyl levulinate by a published procedure.20 Commercial
(S)ꢀ and (R)ꢀBINAP, [RuCl2(COD)]n, [RuCl((R)ꢀBINAP)(pꢀ
1. T. Naota, H. Takaya, and S.ꢀI. Murahashi, Chem. Rev.,
1998, 98, 2599.
2. D. J. Ager and S. A. Laneman, Tetrahedron Asymmetry, 1997,
8, 3327.
MeC6H4Pri)]Cl
(Fluka);
Ru(COD)(MA)2
(Acros);
3. R. Noyori, Acta Chem. Scand., 1996, 50, 380.
4. K. Mashima, K. Kusano, N. Sato, Y. Matsumura, K. Nozaki,
H. Kumobayashi, N. Sayo, Y. Hori, T. Ishizaki,
S. Akutagawa, and H. Takaya, J. Org. Chem., 1994, 59, 3064.
5. W. Tang and X. Zhang, Chem. Rev., 2003, 103, 3045.
6. T. Ohkuma, M. Kitamura, and R. Noyori, Tetrahedron Lett.,
1990, 31, 5509.
7. K. Tohdo, Y. Hamada, and T. Shioiri, Synlett, 1994, 105.
8. S. A. King, J. Org. Chem., 1994, 59, 2253.
9. E. L. Stangeland and T. Sammakia, J. Org. Chem., 2004,
69, 2381.
(R,R)ꢀPriꢀDuPHOS, (S,S)ꢀBPE, and (R)ꢀProphos (Strem) were
used. The complex [RuCl2(C6H6)]2 was synthesized from RuCl3
and 1,3ꢀcyclohexadiene (Fluka) by a reported procedure.21 Prior
to use, all solvents were dehydrated and distilled in an argon
flow, which was purified by passing through columns containing
a nickelꢀchromium catalyst, copper supported on Kieselguhr
(80 °C), and molecular sieves (4A). Hydrogen was purified by
passing through columns with the nickelꢀchromium catalyst and
molecular sieves.
The composition of the products was determined by NMR
on a Bruker AMꢀ300 instrument. The enantiomeric analysis of
lactone 3 was carried out on a Biochromꢀ21 chromatograph
10. G. Juszkiewicz, M. Asztemborska, and J. Jurczak, Pol.
J. Chem., 2002, 76, 1707.