3406
Table 5. Dynamic kinetic resolution of secondary alcoholsa
Entry Racemic alcohol
Additiveb Yield ee
T. H. Riermeier et al. / Tetrahedron Letters 46 (2005) 3403–3406
2.5 mL toluene and supplemented with 0.25 mmol of
diamine ligand. After 10 min 0.8 mmol of enantiopure
alcohol is added and stirred at 80 °C for 5 h. Yields
and enantioselectivities are determined by GC analysis.
[%]
[%]
1
2
3
4
5
6
7
8
1-indanol
1-indanol
ꢀ
+
ꢀ
+
ꢀ
+
ꢀ
+
72
93
58
64
59
66
72
80
98
98
98
96
93
97
96
98
4.2. Dynamic kinetic resolution
methyl-2-naphthylmethanol
methyl-2-naphthylmethanol
4-methoxy-1-phenylethanol
4-methoxy-1-phenylethanol
1-phenylethanol
Fifteen milligrams (0.025 mmol) of di-l-chlorobis((p-
cymene)chlororuthenium(II)) is suspended in 2.5 mL
toluene and supplemented with 0.25 mmol of
N,N,N0,N0-tetramethyl-1,3-propanediamine. After 10
min 0.8 mmol of racemic secondary alcohol is added,
if necessary 0.4 mmol of the corresponding ketone,
1.8 mmol p-chlorophenyl acetate and 60 mg of Chira-
zymeÒ l-2, c-f, lyo. The reaction mixture is stirred for
45 h at 80 °C. Yields and enantioselectivities are deter-
mined by GC analysis.
1-phenylethanol
a Reagents and conditions: 0.025 mmol [Ru(cymene)Cl2]2, 0.25 mmol
2d, 0.8 mmol rac-alcohol
b 0.4 mmol of the corresponding ketone.
dynamic kinetic resolution of aromatic secondary alco-
hols. With this easy to handle catalyst system nearly
the same activities and selectivities were obtained com-
pared to the catalytic systems introduced by Ba¨ckvall,
Kim or Sheldon. Our system has a strong preference
to aromatic alcohols so that it complements the Ba¨ck-
vall system with its preference for aliphatic alcohols
and hydroxy esters.15 Even the restriction to allylic alco-
hols, which was the limitation of ruthenium–cymene
based catalysts, was overcome.4,9 Furthermore, the here-
in introduced catalytic system is characterized by its sim-
plicity of synthesis and its robustness.
References and notes
1. Faber, K. Chem. Eur. J. 2001, 7, 5004–5010; Strauss, U.
T.; Felfer, U.; Faber, K. Tetrahedron: Asymmetry 1999,
10, 107–117.
2. Kim, M.-J.; Ahn, Y.; Park, J. Curr. Opin. Biotechnol.
2002, 13, 578–587; Huerta, F. F.; Minidis, A. B. E.;
Ba¨ckvall, J.-E. Chem. Soc. Rev. 2001, 30, 321–331.
3. Dinh, P. M.; Howarth, J. A.; Hudnott, A. R.; Williams, J.
M. J.; Harris, W. Tetrahedron Lett. 1996, 37, 7623–
7626.
3. Conclusion
4. Allen, J. V.; Williams, J. M. J. Tetrahedron Lett. 1996, 37,
1859–1862; Choi, Y. K.; Suh, J. H.; Lee, D.; Lim, I. T.;
Jung, J. Y.; Kim, M.-J. J. Org. Chem. 1999, 64, 8423–
8424.
5. Larsson, A. L. E.; Persson, B. A.; Ba¨ckvall, J.-E. Angew.
Chem., Int. Ed. 1997, 36, 1211–1212; Persson, B. A.;
Larsson, A. L. E.; Le Ray, M.; Ba¨ckvall, J.-E. J. Am.
Chem. Soc. 1999, 121, 1645–1650.
6. Edin, M.; Steinreiber, J.; Ba¨ckvall, J. E. Proc. Natl. Acad.
Sci. U.S.A. 2004, 101, 5761–5766.
7. Koh, J. H.; Jung, H. M.; Kim, M.-J.; Park, J. Tetrahedron
Lett. 1999, 4, 6281–6284.
8. Choi, J. H.; Kim, Y. H.; Nam, S. H.; Shin, S.; Tae,
K. M.-J.; Park, J. Angew. Chem., Int. Ed. 2002, 41, 2373–
2376; Choi, J.; Ho, C.; Yoon, K.; Kim, Y. H.; Park,
E. S.; Kim, E. J.; Kim, M.-J.; Park, J. J. Org. Chem. 2004,
69, 1972–1977.
In this letter we describe an alternative catalytic system
for the dynamic kinetic resolution of secondary alcohols
on ruthenium basis. At first, a racemization active in situ
mixture consisting of the ruthenium precursor [Ru(cym-
ene)Cl2]2 and readily available diamines was developed,
which is distinguished by its easy synthesis and stability
towards air and moisture. Especially N,N,N0,N0-tetra-
methyl-1,3-propanediamine as ligand gives excellent
racemization activity. This racemization catalyst is com-
bined with lipase-catalyzed kinetic resolution using
p-chlorophenyl acetate as acyl donor with good perfor-
mance for the dynamic kinetic resolution of secondary
alcohols.
9. Lee, D.; Huh, E. A.; Kim, M.-J.; Jung, H. M.; Koh, J. H.;
Park, J. Org. Lett. 2000, 2, 2377–2379.
10. Crabtree, R. H.; Pearman, A. J. J. Organomet. Chem.
1977, 141, 325–330.
4. Materials and methods
All chemicals were purchased at Sigma–Aldrich and
used without prior purification. ChirazymeÒ l-2, c-f,
lyo. was obtained from Roche and Biocatalytics. Yields
and enantioselectivities were determined by GC-analysis
with an Agilent 6890, CP-Chirasil-DEX-CB, 140 °C ini-
tial temperature, 200 °C final temperature, 15 °C/min.
0.1 mL hexadecane was used as internal standard.
11. Dijksman, A.; Elzinga, J. M.; Li, Y.-X.; Arends, I. W. C.
E.; Sheldon, R. A. Tetrahedron: Asymmetry 2002, 13, 879–
884.
12. Kim, J. H.; Jeong, H. M.; Park, J. Tetrahedron Lett. 1998,
39, 5545–5548.
13. Kim, M.-J.; Chung, Y. I.; Choi, Y. K.; Lee, H. K.; Kim,
D.; Park, J. J. Am. Chem. Soc. 2003, 125, 11494–
11495.
14. Keller, R.; Holla, W.; Fuelling, G. EP 321918, 1989.
15. Huerta, F. F.; Laxmi, Y. R. S.; Ba¨ckvall, J.-E. Org. Lett.
2000, 2, 1037–1040; Persson, B. A.; Huerta, F. F.;
Ba¨ckvall, J.-E. J. Org. Chem. 1999, 64, 5237–5240; Pamies,
O.; Ba¨ckvall, J.-E. J. Org. Chem. 2002, 67, 1261–1265.
4.1. Racemization experiments
In a Schlenk tube 15 mg (0.025 mmol) of di-l-chloro-
bis((p-cymene)chlororuthenium(II)) are suspended in