Aminocyclopentadienyl ruthenium chloride: Catalytic racemization and dynamic kinetic resolution of alcohols at ambient temperature

Article abstract of DOI:10.1002/1521-3773(20020703)41:13<2373::AID-ANIE2373>3.0.CO;2-7

Ruthenium-enzyme tandem catalysis: The novel racemization catalyst 1 improves the dynamic kinetic resolution (DKR) of secondary alcohols dramatically. The DKR proceeds at room temperature with isopropenyl acetate as an acyl donor. In addition, the DKR is faster even with much less lipase than in previous DKRs.

Full text of DOI:10.1002/1521-3773(20020703)41:13<2373::AID-ANIE2373>3.0.CO;2-7

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[15] R. Ugo, S. Bhaduri, B. F. G. Johnson, A. Khair, A. Pickard, J. Chem.
Soc. Chem. Commun. 1976, 694.
[16] S. Bhaduri, B. F. G. Johnson, A. Khair, I. Ghatak, D. M. P. Mingos, J.
Chem. Soc. Dalton 1980, 1572.
[17] A. R. Middleton, G. Wilkinson, M. B. Hursthouse, N. P. Walker, J.
Chem. Soc. Dalton 1982, 663.
derivative has been determined. The decomposition of these
complexes suggests rate-limiting loss of nitrous oxide leads to
unusual and reactive late-transition-metal terminal oxo inter-
mediates.
[18] R. J. Puddephatt, P. J. Thompson, J. Chem. Soc. Dalton 1976, 2091.
[19] B. Jezowska-Trzebiatowska, J. Hanuza, M. Ostern, J. Ziolkowski,
Inorg. Chim. Acta 1972, 6, 141.
[20] H. Okamura, E. Miki, K. Mizumachi, T. Ishimori, Bull. Chem. Soc.
Jpn. 1976, 49, 666.
[21] R. Bau, I. H. Sabherwal, A. B. Burg, J. Am. Chem. Soc. 1971, 93, 4926.
[22] D. S. Bohle, J. A. Imonigie, J. Org. Chem. 2000, 65, 5685.
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Chem. Commun. 1969, 69.
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[27] I. R. Butler, W. R. Cullen, T. J. Kim, S. J. Rettig, J. Trotter, Organo-
metallics. 1985, 4, 972.
Experimental Section
3a: [Ni(dppf)Cl2],[27] (268 mg) dissolved in CH2Cl2 (15 mL) was treated in
one addition with 1[22] (2 equivalents, 249 mg) suspended in methanol
(60 mL). Rapidlya deep orange color developed and the solution volume
was immediatelyreduced to ca 10 mL byevaporation at ambient temper-
atures. The resulting bright orange crystals were isolated by filtration and
washed with portions of cold methanol (4 Â 10 mL) or until the filtrate was
colorless. Recrystallization of this product from dichloromethane/ethanol
at room temperature returns 243 mg (93% yield) of 3a. Elemental analysis
calcd (%) C34H28FeN2NiO2P2 ¥ 1³2CH2Cl2: C 59.26, H 4.05, N 3.88; found: C
59.43, H 4.28, N 3.64; IR (KBr,): nÄ ˆ 1480 m, 1449 s, 1436 s, 1307 m, 1194 w,
1182 w, 1168 m, 1096 s, 1036 m, 1028 m, 999 w, 983 m, 917 m, 827 w, 799 m,
744.3 s, 692 s, 638 w, 625 m, 556 m, 510, s, 494 s, 471 cmÀ1 m; 1H NMR
(400 MHz, CD2Cl2): d ˆ 7.84 (m, 8H), 7.52 (m, 4H), 7.42 (t, J ˆ 7.3 Hz, 8H),
4.42 (m, 4H), 4.26 ppm (m, 4H); 3P NMR (162 MHz, CD2Cl2): d ˆ
25.0 ppm (s) (UV/Vis: lmax, (emax, mÀ1 cmÀ1) in CH2Cl2: 406 nm (655);
differential scanning calorimetry(DSC): DH ˆ À802 kcal molÀ1 Tonset
ˆ
758C. Crystals suitable for X-ray diffraction were grown from CH2Cl2/
Et2O at À158C.
Crystal data for 3a: C35H28Cl2FeN2NiP2O2, M ˆ 755.99, 143 K, triclinic
≈
space group P1, a ˆ 10.6210(8), b ˆ 11.3831(9), c ˆ 15.515(2) ä, a ˆ
84.021(2), b ˆ 72.745(2), g ˆ 69.790(1)8, Vˆ 1681.0(3) ä3, Z ˆ 2, 1calcd
ˆ
Aminocyclopentadienyl Ruthenium Chloride:
Catalytic Racemization and Dynamic Kinetic
Resolution of Alcohols at Ambient
Temperature**
1.494 MgmÀ3, F(000) ˆ 772, 426 parameters; R1 (wR2) [I > 2s(I)] ˆ 0.064
(0.15), s(GOF) ˆ 0.98. Crystals of 3a were mounted on glass fibers with
epoxyresin and diffraction data was collected on a Bruker Smart CCD
diffractometer equipped with a sealed molybdenum tube which was
monochromated to give l ˆ 0.71073 ä. The structure was solved using
direct methods and refined using full-matrix least-squares on F 2 with
SHELXTL. With the exception of the disordered dichloromethane solvate,
all non-hydrogen atoms were refined anisotropically with element assign-
ments as described in the text. CCDC-176081 (3a) contains the supple-
mentarycrystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge
CB21EZ, UK; fax: (‡44)1223-336-033; or deposit@ccdc.cam.ac.uk).
Jun Ho Choi, Yu Hwan Kim, Se Hyun Nam,
Seung Tae Shin, Mahn-Joo Kim,* and Jaiwook Park*
Dynamic kinetic resolution (DKR) is an attractive method
for the complete transformation of a racemic mixture into a
single enantiomer.[1] The DKR of secondaryalcohols is a
prominent example, for which transition-metal-catalyzed
racemization is coupled with enzymatic acylation.[2] In partic-
ular, B‰ckvall and co-workers have introduced a notable
catalyst system that provides a wide range of chiral acetates in
Received: February26, 2002 [Z18780]
f]
good yields and excellent optical purities.[2b However, the
[1] T. R. Ward, R. Hoffmann, M. Shelef, Surf. Sci. 1993, 289, 85.
[2] B. C. Berks, S. J. Ferguson, J. W. B. Moir, D. J. Richardson, Biochim.
Biophys. Acta 1995, 1232, 97.
[3] M. N. Hughes, Q. Rev. Chem. Soc. 1968, 22, 1.
[4] N. Arulsamy, D. S. Bohle, J. A. Imonigie, E. S. Sagan, Inorg. Chem.
1999, 38, 2716.
[5] A. M. Al-Ajlouni, E. S. Gould, J. Chem. Soc. Dalton Trans. 2000, 1239.
[6] M. R. Goyal, P. Bhatnagar, R. K. Mittal, Y. K. Gupta, Indian J. Chem.
Sect. A 1989, 28, 280.
[7] M. R. Goyal, P. Bhatnagar, R. K. Mittal, Y. K. Gupta, Indian J. Chem.
Sect. A 1989, 28, 382.
catalyst for the racemization of secondary alcohols is acti-
vated at high temperature, and needs the corresponding
ketones as hydrogen mediators.[3] Thus, the catalyst system
requires a thermallystable lipase; p-chlorophenyl acetate has
been selected as an acyl donor,[2c] because oxidation of the
starting alcohols occurs when the conventional alkenyl
acetates are used as acyl donors.[4]
[*] Prof. J. Park, Prof. M.-J. Kim, J. H. Choi, Y. H. Kim, S. H. Nam,
S. T. Shin
[8] M. N. Hughes, P. E. Wimbledon, G. Stedman, J. Chem. Soc. Dalton
Trans. 1989, 533.
[9] N. Arulsamy, D. S. Bohle, J. A. Imonigie, E. S. Sagan, J. Am. Chem.
Soc. 2000, 122, 5539.
National Research Laboratoryof Chirotechnology
Department of Chemistry
Division of Molecular and Life Sciences
Pohang Universityof Science and Technology(POSTECH)
San 31 Hyoja Dong, Pohang 790-784 (Korea)
Fax : (‡82)54-279-3399
[10] C. Feldmann, M. Jansen, Angew. Chem. 1996, 108, 1807; Angew.
Chem. Int. Ed. Engl. 1996, 35, 1728.
[11] C. Feldmann, M. Jansen, Z. Anorg. Allg. Chem. 1997, 623, 1803.
[12] S. Bhaduri, B. F. G. Johnson, A. Pickard, P. R. Raithby, G. M.
Sheldrick, C. I. Zuccaro, J. Chem. Soc. Chem. Commun. 1977, 354.
[13] S. Bhaduri, B. F. G. Johnson, C. J. Savory, J. A. Segal, R. H. Walter, J.
Chem. Soc. Chem. Commun. 1974, 809.
E-mail: mjk@postech.ac.kr, pjw@postech.ac.kr
[**] We are grateful for the financial support from MOST through the
NRL program, KOSEF through the Center for Integrated Molecular
System, and the Korean Ministry of Education through the BK21
project for our graduate program.
[14] S. Cenini, R. Ugo, G. La Monica, S. D. Robinson, Inorg. Chim. Acta
1972, 6, 182.
Angew. Chem. Int. Ed. 2002, 41, No. 13
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Herein we report a novel ruthenium catalyst that can
racemize secondaryalcohols efficientlyat room temperature
without the aid of hydrogen mediators.[5, 6] Furthermore, the
catalytic racemization is compatible with the use of isopro-
penyl acetate for the DKR of secondary alcohols at room
temperature (Scheme 1).
We expected the generation of a coordinativelyunsaturated
and active species bythe elimination of hydrogen chloride
from 1 with a proper base.[8] Indeed, (S)-1-phenylethanol
(>99% ee) was racemized completelywithin 30 min at 25 8C
bythe catalytic species generated bythe treatment of 1 with
potassium tert-butoxide. The scope of the catalytic racemiza-
tion was investigated under various conditions (Ta-
ble 1): The racemization rate is not affected signifi-
cantlybythe polarityand the coordinating abilityof
solvents (entries 1 4, though it is slightlyslower with
acetone). Even without solvent, the racemization is
practicallycompleted in 12 h with only0.3 mol% of
1 (entry5). Notably, the catalytic species is still active
in the presence of vinyl acetate in toluene (entry 6),
although the racemization is almost prevented when
vinyl acetate alone is employed as a solvent (entry 7).
On the basis of the racemization results, the DKR
of 1-phenylethanol was investigated with varying
conditions (Table 2): Unexpectedly, the DKR is
unsuccessful under the racemization conditions of
the entry6 in Table 1 despite the fact that the lipase itself does
not interfere with the catalytic racemization. A breakthrough
is the use of sodium carbonate or 4-ä molecular sieve as an
additive (Table 2 entries 2 and 3). Isopropenyl acetate is a
better acyl donor than vinyl acetate it gives faster and more
productive DKR. Increasing temperature makes the DKR
faster, but the production of acetophenone increases: 1.6% at
258C, 2.5% at 408C, and 10.4% at 708C (entries 4 6). In the
Scheme 1. Synthesis of 1 and DKR of 1-phenylethanol; MS ˆ molecular sieve.
For the synthesis of aminocyclopentadienyl ruthenium
chloride (1), it was fortunate to select chloroform as the
solvent in the reaction of [Ru3(CO)12] with the imine prepared
from isopropylamine and 2,3,4,5-tetraphenylcyclopentadie-
none. Attempts at synthesizing the tricarbonyl analogue
under various other reaction conditions failed. The molecular
structure of 1 was confirmed byX-raydiffraction analysis
(Figure 1).[7]
Table 1. Catalytic racemization of (S)-1-phenylethanol at 258C after
activating 1 with potassium tert-butoxide.[a]
EntrySolvent
t [h]
ee[b] [%]
1
2
3
4
5
6
7
toluene
CH2Cl2
THF
acetone
no solvent[c]
toluene ‡ vinyl acetate[d]
vinyl acetate
0.5
0.5
0.5
0.5
12
0.0
0.0
0.0
24.7
1.8
6.8
1.0
5.0
96.4
[a] (S)-1-Phenylethanol (>99% ee, 0.25 mmol) dissolved in
a
solvent
(0.80 mL) was added to a flask containing 1 (6.2 mg, 4.0 mol%) and
potassium tert-butoxide (0.013 mmol, 5.2 mol%). [b] Measured byHPLC
equipped with a chiral column (Chiralcel OD, Daicel). [c] (S)-1-Phenyl-
ethanol (>99% ee, 0.40 mL, 3.3 mmol) was added to a flask containing 1
(6.2 mg, 0.30 mol%) and potassium tert-butoxide (0.013 mmol,
0.40 mol%). [d] Toluene (0.80 mL) was mixed with vinyl acetate
(0.38 mmol, 1.5 equiv).
Figure 1. ORTEP plot (thermal ellipsoids set at 50% probability) of the
molecular structure of 1. All hydrogen atoms are omitted for clarity.
Selected bond lengths [ä] and angles [8]: Ru(1)-Cl(1) 2.4137(8), Ru(1)-
C(4) 2.430(3), N(1)-C(4) 1.339(3), N(1)-C(30) 1.467(3); Cl(1)-Ru(1)-C(4)
86.96(7), Ru(1)-C(4)-N(1) 131.6(2), C(4)-N(1)-C(30) 128.4(2).
Table 2. Dynamic kinetic resolution of 1-phenylethanol.[a]
[b]
ElndtroynAorcy
Lipase[c] [mg]
Additive[d]
T [8C]
t [h]
Acetate [%][e]
ee[f] [%]
ˆ
1
2
3
4
5
6
7
CH2 CHOCOCH3
0.7
0.7
0.7
0.7
0.7
0.7
7
25
25
25
25
40
70
25
96
96
40
30
24
12
42
55
89
98
97
95
90
95
98.6
97.0
98.5
> 99
> 99
> 99
> 99
ˆ
CH2 CHOCOCH3
Na2CO3
molecular sieve 4 ä
Na2CO3
Na2CO3
Na2CO3
ˆ
CH2 C(CH3)OCOCH3
ˆ
CH2 C(CH3)OCOCH3
ˆ
CH2 C(CH3)OCOCH3
ˆ
CH2 C(CH3)OCOCH3
[g]
p-ClC6H4OCOCH3
Na2CO3
[a] The reactions were carried out with 0.25 mmol of 1-phenylethanol and 4 mol% of 1, which was activated with 5 mol% of potassium tert-butoxide, in dry
toluene (0.80 mL) under argon atmosphere. [b] 1.5 equiv of alkenyl acetate [c] Novozym 435. [d] Sodium carbonate (1.0 equiv) or molecular sieve 4 ä
(60 mg) was used. [e] The yields were determined by GC. [f] The % ee values were determined byHPLC equipped with a chiral column (( R,R) Whelk-01,
Merck). [g] 3 equiv.
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DKR with p-chlorophenyl acetate, the reaction proceeds
more slowlyeven with ten times more lipase (entry7). This
result clearlyshows the advantage of isopropenyl acetate over
p-chlorophenyl acetate as the acyl donor. Furthermore, the
use of isopropenyl acetate makes the isolation of the acylated
product much easier than with p-chlorophenyl acetate.[9]
Our catalyst system was effective also for the DKR of other
aromatic alcohols and aliphatic alcohols (Table 3): Substitu-
ent effects are insignificant in the DKR of aromatic alcohols
while the DKR of aromatic alcohols is somewhat faster than
that of aliphatic alcohols.
during the racemization in acetone is explained bythe slow
exchange of ketones in 3. Meanwhile, it is not clear yet why
the racemization is inhibited significantlyduring the DKR
without sodium carbonate or molecular sieves. A possible
cause for the inhibition is the formation of acetic acid from the
reaction of the acetylated lipase and water during the DKR.
In a separate experiment, we observed that the racemization
of 1-phenylethanol was inhibited by the addition of acetic acid
and then recovered slowlybythe subsequent addition of
sodium carbonate.[10, 11]
In summary, we have demonstrated highly efficient race-
mization and DKR of secondaryalcohols bythe use of a novel
ruthenium catalyst compatible with enzymatic resolution. The
new mode of our catalytic racemization allows the use of more
reactive isopropenyl acetate as an acyl donor and thus much
less lipase. Furthermore, the simple method for the prepara-
tion of the catalyst can be applied for the development of
more practical catalysts.
Table 3. Dynamic kinetic resolution of various alcohols.[a]
[b]
EntryAlcohol
t [h]
Acetate[b]
ee [%]
1
2
3
4
5
1-(p-chlorophenyl)ethanol
1-(p-methoxyphenyl)ethanol
1-indanol
1-cyclohexylethanol
2-octanol
48
48
48
72
72
94%
90%
89%
86%
89%
> 99[c]
> 99[c]
95.0[d]
> 99[e]
90.5[e]
[a] The reactions were carried out with 1.00 mmol of an alcohol under the
conditions of the entry4 in Table 2. [b] Yields of isolated product. [c] By
HPLC ((R,R) Whelk-01, Merck). [d] By HPLC after hydrolysis to
1-indanol (Chiralcel OD, Daicel). [e] ByGC (Chiraldex B-PH, Alltech).
Experimental Section
1: In a 100-mL flask equipped with a grease-free high-vacuum stopcock,
[Ru3(CO)12] (1.0 g, 1.6 mmol) and the imine (1.0 g, 2.4 mmol) prepared
from isopropylamine and 2,3,4,5-tetraphenylcyclopentadienone were dis-
[12]
solved in dry, degassed chloroform (30 mL). After the flask was filled
The observations recorded in Table 1 require a mechanism
different from those involving simple hydrogen-transfer
reactions for the catalytic racemization. In particular, the
slow down of the racemization in acetone cannot be explained
bythe mechanisms involving ketones as hydrogen mediators.
It is also notable that acetophenone was produced in only
about 7% during the racemization in acetone. Thus, it is
proposed that the racemization occurs during the reversible
transformation between a ruthenium alcohol complex (2)
and a ruthenium ketone complex (3; Scheme 2). The equi-
librium would shift towards 2, which exchanges alcohols
rapidlyat room temperature. The low yield of acetophenone
with Ar and closed, the solution was stirred at 908C for 5 days. The reaction
mixture was concentrated and purified bychromatographyon a silica-gel
column to give yellow solid 1 (691 mg, 47% yield). The solid was
recrystallized from CH2Cl2/Et2O. m.p. 1978C (dec.); 1H NMR (CDCl3;
300 MHz): d ˆ 7.57 6.91 (m, 20H), 4.20 (d, J ˆ 4.1 Hz, 1H), 3.3 3.23 (m,
1H), 0.86 ppm (d, J ˆ 3.2 Hz, 6H); 13C NMR (CDCl3; 75 MHz): d ˆ 198.4,
144.8, 133.7, 131.9, 130.6, 128.9, 128.7, 128.2, 127.7, 101.4, 81.7, 45.6,
25.2 ppm; IR (KBr, cmÀ1): nÄ(CO) ˆ 2017 (S), 1963 (s); MS (FAB, m/z):
‡
619.6(M ); elemental analysis (%) calcd for C34H28NO2ClRu: C 65.96, H
4.56, N 2.26; found: C 65.77, H 4.60, N 2.11.
Dynamic kinetic resolution of 1-phenylethanol: A solution of potassium
tert-butoxide (1m in THF; 52 mL, 0.050 mmol) was added to a 50-mL flask
equipped with a grease-free high-vacuum stopcock. The THF was removed
under vacuum, and the flask was filled with argon. Then, 1 (24.8 mg,
0.04 mmol), Novozym 435 (2.8 mg; Novo Nordisk), Na2CO3
(104 mg, 1.00 mmol), a solution of 1-phenylethanol (120 mL,
1.00 mmol) in toluene (3.2 mL), and isopropenyl acetate
(168 mL, 1.5 mmol) were added sequentiallyunder argon. After
being stirred at 258C for 30 h, the reaction mixture was
concentrated and purified bychromatographyon a silica-gel
column (ethyl acetate/hexane 1:8) to give (R)-1-phenylethyl
acetate (156 mg, 95% yield, >99% ee).
Received: February14, 2002
Revised: April 22, 2002 [Z18712]
[1] For recent reviews, see: a) R. Noyori, M. Tokunaga, K.
Kitamura, Bull. Chem. Soc. Jpn. 1995, 68, 36; b) R. S.
Ward, Tetrahedron: Asymmetry 1995, 6, 1475; c) S. Cad-
dick, K. Jenkins, Chem. Soc. Rev. 1996, 447; d) R. St¸rmer,
Angew. Chem. 1997, 109, 1221; Angew. Chem. Int. Ed.
Engl. 1997, 36, 1173; e) U. T. Strauss, U. Felfer, K. Faber,
Tetrahedron: Asymmetry 1999, 10, 107; f) F. F. Huerta,
A. B. E. Minidis, J.-E. B‰ckvall, Chem. Soc. Rev. 2001, 30,
321.
[2] a) P. M. Dinh, J. A. Howarth, A. R. Hudnott, J. M. J.
Williams, W. Harris, Tetrahedron Lett. 1996, 37, 7623;
b) A. L. E. Larsson, B. A. Persson, J.-E. B‰ckvall, Angew.
Chem. 1997, 109, 1256; Angew. Chem. Int. Ed. Engl. 1997,
Scheme 2. Proposed mechanism for the catalytic racemization of secondary alcohols.
36, 1211; c) B. A. Persson, A. L. E. Larsson, M. L. Ray,
Angew. Chem. Int. Ed. 2002, 41, No. 13 ¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4113-2375 $ 20.00+.50/0
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COMMUNICATIONS
J.-E. B‰ckvall, J. Am. Chem. Soc. 1999, 121, 1645; d) B. A. Persson,
F. F. Huerta, J.-E. B‰ckvall, J. Org. Chem. 1999, 64, 5237; e) F. F.
Huerta, Y. R. S. Laxmi, J.-E. B‰ckvall, Org. Lett. 2000, 2, 1037; f) F. F.
Huerta, J.-E. B‰ckvall, Org. Lett. 2001, 3, 1209; g) J. H. Koh, H. M.
Jeoung, M.-J. Kim, J. Park, Tetrahedron Lett. 1999, 40, 6281; h) H. M.
Jeong, J. H. Koh, M.-J. Kim, J. Park, Org. Lett. 2000, 2, 2487; i) H. M.
Jeong, J. H. Koh, M.-J. Kim, J. Park, Org. Lett. 2000, 2, 409; j) M.-J.
Kim, D. Lee, E. A. Huh, H. M. Jeong, J. H. Koh, J. Park, Org. Lett.
2000, 2, 2377; k) M.-J. Kim, Y. K. Choi, M. Y. Choi, M. J. Kim, J. Park,
J. Org. Chem. 2001, 66, 4736.
Chiral Epoxides by Desymmetrizing
Deprotonation of meso-Epoxides**
David M. Hodgson* and Emmanuel Gras
Epoxides are widelyutilized as versatile synthetic inter-
mediates, and the epoxide functional group is also found in a
number of interesting natural products.[1] Therefore, the
development of efficient (especiallyasmy metric) methods
for the elaboration of epoxides is an important ongoing
challenge.[2] In contrast to chemistryexploiting the electro-
philic nature of epoxides, the utilityof epoxides as nucleo-
philes (via oxiranyl anions, eg 1-Li), first studied byEisch and
Galle,[3] is less developed.[4] A current requirement with this
latter strategyis that the epoxide must possess an activating
substituent (electron-withdrawing, trialkylsilyl, or trialkyl-
stannyl group) attached to the epoxide ring. Electron-with-
drawing and trialkylsilyl substituents facilitate the formation
of oxiranyl anions by promoting deprotonation (usually
lithiation) and prolonging the solution lifetime of these
otherwise very labile intermediates. Trialkylstannyl- and
sulfinyl-substituted epoxides react with organolithium species
(by transmetalation and desulfinylation, respectively) rapidly
enough at low temperatures, such that the resultant unstabi-
lized oxiranyl anions can exhibit synthetically useful nucleo-
philic (rather than carbene-type) reactivity with a range of
electrophiles.[5] Such reactions demonstrate the value of
oxiranyl-lithium species as important intermediates in the
elaboration of epoxides, but theyalso indicate the potential
limitation of requiring an activated epoxide precursor to carry
out the chemistry.
[3] In reference [2g], we have reported an exceptional case that does not
require hydrogen mediators. However, oxygen, a base, and high
reaction temperature were necessaryto generate catalytic species.
[4] In references [2h] and [2i], we have described the use of alkenyl
acetates as substrates and acyl donors in the presence of proper
hydrogen donors.
[5] For a review about racemization, see: E. J. Ebbers, G. J. A. Ariaans,
J. P. M. Houbiers, A. Braggink, B. Zwanenburg, Tetrahedron 1997, 53,
9417.
[6] We have found a catalyst system for the racemization of secondary
alcohols at room temperature without the aid of hydrogen mediators.
However, the catalyst system requires strong bases, and is not
compatible with enzymatic acylation: J. H. Koh, H. M. Jeong, J. Park,
Tetrahedron Lett. 1998, 39, 5544.
[7] Crystal data for 1: C34H28ClNO2Ru. Mr ˆ 619.09 gmolÀ1. Orange
crystal: size 0.50  0.20  0.20 mm3, orthorhombic, a ˆ 20.1560(13),
b ˆ 13.2405(9), c ˆ 21.1819(14) ä, a ˆ 90, b ˆ 90, g ˆ 908, space group
Pbca, Vˆ 5652.9(6) ä3, Z ˆ 8, Tˆ 223(2) K, 1calcd ˆ 1.455 gcmÀ3, ab-
sorption coefficient ˆ 0.681 mmÀ1. Siemens SMART diffractometer,
l ˆ 0.71073 ä, scan mode-w (w-scan width: 1.92 to 23.338). 22982
reflections were measured, giving 4077 unique data with I > 2s(I).
R ˆ 0.0252, Rw ˆ 0.0592, GOF ˆ 1.004. CCDC-179224 (1) contains the
supplementarycrystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html
(or from the Cambridge Crystallographic Data Centre, 12, Union
Road, Cambridge CB21EZ, UK; fax: (‡44)1223-336-033; or deposit
@ccdc.cam.ac.uk).
[8] For examples of activating catalyst precursors by treatment with
proper bases, see: K.-J. Haack, S. Hashiguchi, A. Fujii, T. Ikariya, R.
Noyori, Angew. Chem. 1997, 109, 297; Angew. Chem. Int. Ed. Engl.
1997, 36, 285, and references therein.
Recently, we showed that direct lithiation of terminal
epoxides, followed byelectrophile trapping of the nonstabi-
lized oxiranyl anion intermediates, was possible in the
presence of a diamine ligand.[6] However, the reaction was
restricted to silylation (with TMSCl; TMS ˆ trimethylsilyl)
present during generation of the oxiranyl anion) and deuter-
ation (MeOD as an external electrophile). Here we report the
first examples of unactivated epoxides undergoing direct
deprotonation to give destabilized (alkyl-substituted) oxiran-
yl anions, and their subsequent trapping with a range of
[9] The separation of the product from unreacted p-chlorophenyl acetate
is difficult in some cases.[2c]
[10] When 5 mol% of acetic acid was added to the mixture given in entry1
in Table 1, the optical purityof 1-phenlyethanol changed onlyto
69.0% ee in 30 min. However, the racemization was completed in 5 h
bythe subsequent addition of sodium carbonate (1 equiv).
[11] A
related
complex,
[{2,5-Ph2-3,4-tol2(h5-C4COH)}Ru(CO)2-
(O2CCF3)], is formed in the reaction of [{2,5-Ph2-3,4-tol2(h4-C4CO)-
Ru(CO)2}2] and trifluoroacetic acid: C. P. Casey, S. W. Singer, D. R.
Powell, R. K. Hayashi, M. Kavana, J. Am. Chem. Soc. 2001, 123, 1090.
[12] The imine was prepared in 90% yield according to the procedure
described byW. Dai, R. Strinivasan, J. A. Katzenellenbogen, J. Org.
Chem. 1989, 54, 2204. Physical properties of the imine: m.p.: 2238C;
1H NMR (CDCl3): d ˆ 7.25 6.75 (m, 20H), 4.08 4.00 (m, 1H),
1.04 ppm (d, J ˆ 3 Hz, 6H); 13C NMR (CDCl3): d ˆ 165.8, 137.6, 131.9,
130.2, 129.8, 128.2, 127.8, 127.4, 127.2, 127.1, 126.5, 52.3, 24.6 ppm; MS
À
electrophiles (including C C-bond formation). Furthermore,
a new enantioselective approach to substituted epoxides is
demonstrated: symmetry breaking by asymmetric lithia-
tion[7, 8] electrophile trapping, at an epoxide functionality
fused to eight- and seven-membered rings.
‡
(FAB, m/z): 425.27 (M ); elemental analysis (%) calcd for C32H27N: C
[*] Dr. D. M. Hodgson, Dr. E. Gras
Dyson Perrins Laboratory
90.31, H 6.39, N 3.29; found: C 90.26, H 6.62, N 3.14.
Universityof Oxford
South Parks Road, Oxford, OX1 3QY (UK)
Fax : (‡44)1865-275-674
E-mail: david.hodgson@chem.ox.ac.uk
[**] This work was supported bythe Engineering and Physical Sciences
Research Council (EPSRC) in the U.K. and bya Marie Curie
Fellowship of the European Community(program TMR under
contract number HPMF-CT-2000-00558). We also thank the EPSRC
National Mass SpectrometryService Centre for mass spectra, and I. D.
Cameron for preliminaryobservations.
Supporting information for this article is available on the WWW under
http://www.angewandte.org or from the author.
2376
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4113-2376 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 13