Atropos but Achiral Tris(phosphanyl)biphenyl Ligands for Ru-Catalyzed Asymmetric Hydrogenation

Article abstract of DOI:10.1002/anie.200352277

Axial chirality is generated upon complexation of the novel triphos ligand with a metal. In the presence of the diamine dm-dabn, isomerization to the enantiopure triphos-Ru complex was observed. The dm-dabn ligand of the Ru complex exchanges with dpen at

Full text of DOI:10.1002/anie.200352277

Angewandte
Chemie
Atropisomerism
Atropos but Achiral Tris(phosphanyl)biphenyl
Ligands for Ru-Catalyzed Asymmetric
Hydrogenation**
Kohsuke Aikawa and Koichi Mikami*
In modern synthetic and pharmaceutical chemistry, the
advance of asymmetric catalysts is of central importance.[1]
The design of chiral ligands is the key to attaining high
asymmetric induction and to increasing catalytic activity from
an achiral precatalyst (“ligand-accelerated catalysis”).[2] How-
[*] Prof. Dr. K. Mikami, K. Aikawa
Department of Applied Chemistry
Graduate School of Science and Engineering
Tokyo Institute of Technology
Ookayama, Meguro-ku, Tokyo 152-8552 (Japan)
Fax: (+81)3-5734-2776
E-mail: kmikami@o.cc.titech.ac.jp
[**] K. Aikawa is grateful to the Japan Society for the Promotion of
Science for Young Scientists for a research fellowship.
Angew. Chem. Int. Ed. 2003, 42, 5455 –5458
DOI: 10.1002/anie.200352277
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5455

Communications
ever, to obtain enantiopure forms of atropisomeric (from
Greek atropos; a = not, tropos = turn)ligands, asymmetric
synthesis or resolution is requisite. In contrast, we reported a
new strategy for asymmetric catalysis with chirally flexible
process is different from that of the biphep–Ru complex. At
low temperatures, the monophosphane part might dissociate
easily, but should re-form the identical enantiomer upon
recomplexation with the metal (Scheme 3, Path A). At higher
[3]
(tropos)2,2
’-bis(diphenylphosphanyl)biphenyl
(biphep)ligands. [3,4] The chirality of the biphep–Ru
complex can be controlled through isomerization
by (S,S)-1,2-diphenylethylenediamine ((S,S)-dpen)
as a chiral controller. As a result, a 2:1 mixture of
S,S,S and R,S,S diastereomers was formed at room
temperature (Scheme 1).[4c,5] The isomerization of
the [biphep–Ru–dpen] complex could take place
À
through disconnection of a Ru P bond followed by
the rotation of the biphenyl rings, and then
[4c,6]
À
recoordination of the Ru P bond (Scheme 1).
Herein we report a novel strategy that employs
atropos but achiral triphos (2,6,2’-tris(diphenyl-
phosphanyl)biphenyl) ligands for Ru catalysts
through chiral control by chiral diamines
(Scheme 2). The three ortho substituents of the
biphenyl compound prevent rotation about the
single bond,[7] but axial chirality is created upon
complexation with a metal.
Scheme 3. Mechanism of isomerization of the triphos–Ru complex.
A racemic and atropos binap–Ru complex gives
a 1:1 mixture of two diastereomers when combined
temperatures, the bisphosphane portion can dissociate to give
the opposite enantiomer (Scheme 3, Path B).
First, the complexation of the triphos–Ru complex and
enantiopure (S,S)-dpen was examined to give a mixture of
[8]
diastereomers in a kinetic (1:1)ratio (see below.)
Next,
isomerization was attempted to convert the diastereomeric
mixture of [(S)-triphos–Ru–(S,S)-dpen] and [(R)-triphos–Ru–
(S,S)-dpen] (1:1) into a single diastereomer. Unfortunately,
no change was observed in the diastereomeric ratio at room
temperature or even at 808C. Similarly, the 1:1 diastereomeric
mixture of [triphos–Ru–dabn] (dabn = 2,2’-diamino-1,1’-
[9]
binaphthyl)did not isomerize at room temperature. How-
ever, the isomerization did proceed at 808C over 2 hours to
the favorable [(S)-triphos–Ru–(S)-dabn] (S,S/R,S 2.3:1)
(Scheme 4). Upon addition of an equimolar amount of
(S,S)-dpen to the diastereomer mixture, the aliphatic diamine
dpen exchanged with the aromatic diamine dabn without
racemization at room temperature (Scheme 4). In sharp
contrast to [biphep–Ru–dpen], which readily isomerizes, the
triphos ligand of [triphos–Ru–dpen] retained its configuration
under the same conditions. Additionally, heating at 808C for
24 h did not change the 2.3:1 diastereomeric ratio (see above).
The use of 3,3’-dimethyl-2,2’-diamino-1,1’-binaphthyl
(dm-dabn), which can readily discriminate between enan-
tiomers owing to its sterically demanding methyl substi-
tuents,[4b,10] resulted in isomerization to give the diastereopure
triphos–Ru complex (Scheme 5). The combination of racemic
(Æ )-triphos–Ru and an equimolar amount of (S)-dm-dabn
gave the single diastereomer by isomerization of the (R)-
triphos–Ru complex in dichloroethane at 808C.[11] Signifi-
cantly, an equimolar amount of (S,S)-dpen did exchange with
dm-dabn upon addition to the enantiopure complex, to give
enantiopure [(S)-triphos–Ru–(S,S)-dpen] without racemiza-
Scheme 1. Isomerization of the tropos biphep–Ru complex at room
temperature.
Scheme 2. Chiral control of the atropos triphos–M complex.
with an equimolar amount of an enantiopure diamine
controller. However, if biphep is used as a ligand instead of
binap, the diastereomer ratio can be increased up to 2:1, even
at room temperature, by virtue of the tropos nature.[4c]
In spite of the atropos nature, the diastereomer ratio of
the triphos–Ru complex can, in principle, be increased by a
chiral controller (Scheme 3). However, the isomerization
5456
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 5455 –5458

Angewandte
Chemie
tion of the triphos–Ru moiety at room
temperature (Scheme 5).
The enantiopure [triphos–Ru–
dpen] was used in the enantioselec-
tive hydrogenation of a simple ketone
in the presence of KOH (Table 1).[12]
The enantioselectivity observed with
[(Æ )-binap–Ru–(S,S)-dpen][13]
was
higher than that found with chirally
flexible
even after isomerization (Table 1,
entries 1–3).[14]
The [triphos–
[biphep–Ru–(S,S)-dpen],
Scheme 4. Isomerization and chiral stability of the triphos–Ru–diamine complexes.
Ru–(S,S)-dpen] complex (d.r. 1:1)
also resulted in lower enantioselec-
tivity (Table 1, entry 4). However, the
enantioselectivity exhibited by enan-
tiopure [(S)-triphos–Ru–(S,S)-dpen]
was much higher than that by [(Æ )-
binap–Ru–(S,S)-dpen] under the
same conditions (Table 1, entries 1
and 5).
In summary, we have demon-
strated that the axial chirality of a
Ru complex with an atropos but
achiral triphos ligand can be control-
led perfectly and retained at room
temperature, in contrast to the tropos
biphep–Ru complex. The enantio-
pure [triphos–Ru–dm-dabn] complex
underwent exchange with dpen with-
out racemization of the triphos–Ru
moiety at room temperature, and the
enantiopure [triphos–Ru–dpen] com-
plex led to higher enantioselectivity
than that attained with (Æ )-binap–Ru
and biphep–Ru complexes in the
asymmetric hydrogenation of
ketone.
a
Scheme 5. Resolution and subsequent isomerization by (S)-dm-dabn, and atropos nature of
the triphos–Ru complex.
Experimental Section
[(S)-triphos–Ru–(S)-dm-dabn]: Degassed
N,N-dimethylformamide (3.5 mL)was
added to a mixture of [{RuCl2(benzene)}2]
(25.0 mg, 0.05 mmol)and triphos (70.7 mg, 0.10 mmol)under an
argon atmosphere in a Schlenk tube. After stirring for 3 h at 1008C,
the clear reddish-brown solution was concentrated at 508C under
reduced pressure. Degassed dichloroethane (5.0 mL)was added to
the mixture of the triphos–Ru complex and (S)-dm-dabn (31.2 mg,
0.10 mmol)under an argon atmosphere in a Schlenk tube. The
solution was stirred for 2 h at 808C and then concentrated under
reduced pressure to give [(S)-triphos–Ru–(S)-dm-dabn] quantita-
tively. 1H NMR (300 MHz, CDCl3): d = 1.82 (s, 3H), 1.85 (s, 3H),
3.94–3.99 (m, 2H; NH2), 4.69 (d, J = 6.6 Hz, 1H; NH2), 4.74 (d, J =
6.6 Hz, 1H; NH2), 5.45–5.47 (m, 1H), 6.19 (t, J = 5.7 Hz, 1H), 6.77–
Table 1: Enantioselective hydrogenation by Ru catalysts with different
phosphane ligands.
Entry
Phosphane
S,S,S/R,S,S[a]
t [h]
ee [%]
Yield [%]
1
2
(Æ)-binap
biphep
biphep
triphos
triphos
1:1
1:1
2:1
1:1
100:0
4
4
4
6
6
71
54
69
66
85
>99
>99
>99
>99
>99
3[b]
4
8.18 ppm (m, 45H); 31P NMR (162 MHz, CDCl3): d = À 11.3 (d, JP-P
=
6.2 Hz, 1P), 44.6 (d, JP-P = 39.7 Hz, 1P), 47.7 ppm (dd, JP-P = 6.2,
39.7 Hz, 1P).
Asymmetric hydrogenation: An autoclave (100 mL)was charged
with solid [(S)-triphos–Ru–(S)-dm-dabn] (14.3 mg, 0.012 mmol) and
(S)-dpen (2.5 mg, 0.012 mmol). After replacing the air in the
5
1
[a] The S,S,S/R,S,S ratio was determined by H and 31P NMR spectros-
copic analysis. [b] [biphep–Ru–(S,S)-dpen] in 2-propanol was prestirred
at room temperature for 3 h.
Angew. Chem. Int. Ed. 2003, 42, 5455 –5458
www.angewandte.org
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5457

Communications
autoclave with argon, degassed CH2Cl2 (2.0 mL)was added. The
53.5 ppm (dd, JP-P = 5.3, 45.0 Hz, 1P); S,S: d = À 11.5 (d, JP-P
=
solution was stirred for 24 h at room temperature, and then
concentrated under reduced pressure. The autoclave was again
charged with an argon atmosphere, and 2-propanol (3.3 mL)and
KOH/2-propanol (0.5m; 48 mL, 0.024 mmol)was added under a
stream of argon. The mixture was stirred for 30 min at room
temperature. 1’-Acetonaphthone (0.46 mL, 3.0 mmol)was added
under a stream of argon, and hydrogen was then introduced at a
pressure of 8 atm. The reaction mixture was vigorously stirred for 6 h
at room temperature. After concentration under reduced pressure,
the residue was filtered through a short column of silica gel. The yield
and ee values were determined by chiral GC analysis. The product was
isolated by column chromatography on silica gel (hexane/EtOAc 3:1)
in 99% yield; GC (column: CP-Cyclodextrin-b-2,3,6-M-19, i.d.
0.25 mm ” 25 m, CHROMPACK; carrier gas: nitrogen 75 kPa;
column temperature: 1608C; injection and detection temperature:
1908C; split ratio: 100:1): tR (S isomer) = 31.6 min, tR (R isomer) =
32.5 min.
5.3 Hz, 1P), 50.3 (d, JP-P = 42.8 Hz, 1P), 52.1 ppm (dd, JP-P = 5.3,
42.8 Hz, 1P).
[10] a)K. Mikami, T. Korenaga, T. Ohkuma, R. Noyori, Angew.
Chem. 2000, 112, 3854 – 3857; Angew. Chem. Int. Ed. 2000, 39,
3707 – 3710; b)K. Mikami, Y. Yusa, T. Korenaga, Org. Lett. 2002,
4, 1643 – 1645.
[11] [(S)-triphos–Ru–(S)-dm-dabn]: 31P NMR (162 MHz, CDCl3):
d = À 11.3 (d, JP-P = 6.2 Hz, 1P), 44.6 (d, JP-P = 39.7 Hz, 1P),
47.7 ppm (dd, JP-P = 6.2, 39.7 Hz, 1P).
[12] Hydrogenation with enantiopure [binap–Ru–dpen]: a)for an
excellent review, see: R. Noyori, T. Ohkuma, Angew. Chem.
2001, 113, 40 – 75; Angew. Chem. Int. Ed. 2001, 40, 40 – 73; see
also: b)T. Ohkuma, H. Ooka, S. Hashiguchi, T. Ikariya, R.
Noyori, J. Am. Chem. Soc. 1995, 117, 2675 – 2676; c)T. Ohkuma,
H. Ooka, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1995, 117,
10417 – 10418.
[13] Examples of asymmetric hydrogenation: a)[( Æ )-tol-binap–Ru–
(S,S)-dpen]: T. Ohkuma, H. Doucet, T. Pham, K. Mikami, T.
Korenaga, M. Terada, R. Noyori, J. Am. Chem. Soc. 1998, 120,
1086 – 1087; b)[( Æ )-dm(xyl)-binap–Ru–(S,S)-dpen]: K. Mikami,
T. Korenaga, Y. Matsumoto, M. Ueki, M. Terada, S. Matsukawa,
Pure. Appl. Chem. 2001, 73, 255 – 259.
Received: July 3, 2003 [Z52277]
Keywords: atropisomerism · chirality · hydrogenation ·
.
phosphane ligands · ruthenium
[14] We have already reported that a Ru complex with a 3,3’-
dimethyl-substituted biphep ligand (dm-biphep)can be con-
trolled to a 3:1 diastereomeric ratio by enantiopure dpen. In
asymmetric hydrogenation, the complex gave a higher enantio-
selectivity than the racemic dm-binap–Ru complex.[4a]
[1] a)E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Comprehensive
Asymmetric Catalysis, Vol. 1–3, Springer, Berlin, 1999; b) Tran-
sition Metals for Organic Synthesis, (Ed.: M. Beller, C. Bolm),
VCH, Weinheim, 1998; c)R. Noyori, Asymmetric Catalysis in
Organic Synthesis, Wiley, New York, 1994; d)H. Brunner, W.
Zettlmeier, Handbook of Enantioselective Catalysis, VCH,
Weinheim, 1993; e) Catalytic Asymmetric Synthesis, Vol. I and
II (Ed.: I. Ojima), VCH, New York, 1993, 2000; f)H. B. Kagan,
Comprehensive Organic Chemistry, Vol. 8, Pergamon, Oxford,
1992; g) Asymmetric Catalysis (Ed.: B. Bosnich), Martinus
Nijhoff Publishers, Dordrecht, 1986.
[2] D. J. Berrisford, C. Bolm, K. B. Sharpless, Angew. Chem. 1995,
107, 1159 – 1171; Angew. Chem. Int. Ed. Engl. 1995, 34, 1059 –
1070.
[3] K. Mikami, K. Aikawa, Y. Yusa, J. J. Jodry, M. Yamanaka,
Synlett 2002, 10, 1561 – 1578.
[4] a)K. Mikami, T. Korenaga, M. Terada, T. Ohkuma, T. Pham, R.
Noyori, Angew. Chem. 1999, 111, 517 – 519; Angew. Chem. Int.
Ed. 1999, 38, 495 – 497; b)K. Mikami, K. Aikawa, T. Korenaga,
Org. Lett. 2001, 3, 243 – 245; c)T. Korenaga, K. Aikawa, M.
Terada, S. Kawauchi, K. Mikami, Adv. Synth. Catal. 2001, 343,
284 – 288; For similar work on the biphep ligand, see: d)M. D.
Tudor, J. J. Becker, P. S. White, M. R. Gagne, Organometallics
2000, 19, 4376 – 4484; e)J. J. Becker, P. S. White, M. R. Gagne, J.
Am. Chem. Soc. 2001, 123, 9478 – 9479.
[5] The diastereomeric ratios were determined by 1H NMR analysis
at 258C in (CD3)2CDOD/CDCl3 (2:1).
[6] M. Yamanaka, K. Mikami, Organometallics 2002, 21, 5847 –
5851.
[7] a)E. L. Eliel, S. H. Wilen, Stereochemistry of Organic Com-
pounds, Wiley, New York, 1994, chap. 14–15; b)“Moleculare
Asymmetrie”: R. Kuhn in Stereochemie (Ed.: H. Freudenberg),
Franz Deutike, Leipzig, 1933, pp. 803 – 824; c)“Recent Advan-
ces in Atropisomerism”: M. Oki, Top. Stereochem. 1983, 14, 1 –
81.
[8] [(Æ )-triphos–Ru–(S,S)-dpen]: 31P NMR (162 MHz, CDCl3):
R,S,S: d = À 11.1 (d, JP-P = 6.2 Hz, 1P), 46.7 (d, JP-P = 36.6 Hz,
1P), 48.0 ppm (dd, JP-P = 6.2, 36.6 Hz, 1P); S,S,S: d = À 10.8 (d,
J
J
P-P = 5.3 Hz, 1P), 46.2 (d, JP-P = 36.6 Hz, 1P), 47.4 ppm (dd,
P-P = 5.3, 36.6 Hz, 1P).
[9] [(Æ )-triphos–Ru–(S)-dabn]: 31P NMR (162 MHz, CDCl3): R,S:
d = À 12.5 (d, JP-P = 5.3 Hz, 1P), 50.9 (d, JP-P = 45.0 Hz, 1P),
5458
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 5455 –5458