Organosilanols as catalysts in asymmetric aryl transfer reactions

Article abstract of DOI:10.1021/ol050242+

(Chemical Equation Presented) Various ferrocene-based organosilanols have been synthesized in four steps starting from achiral ferrocene carboxylic acid. Applying these novel planar-chiral ferrocenes as catalysts in asymmetric phenyl transfer reactions to substituted benzaldehydes afforded products with high enantiomeric excesses. The best result (91% ee) was achieved in the addition to p-chlorobenzaldehyde with organosilanol 2b, which has a tert-butyl substituent on the oxazoline ring and an isopropyl group on the silanol fragment.

Full text of DOI:10.1021/ol050242+

ORGANIC
LETTERS
2005
Vol. 7, No. 7
1407-1409
Organosilanols as Catalysts in
Asymmetric Aryl Transfer Reactions
Salih O2zc¸ubukc¸u, Frank Schmidt, and Carsten Bolm*
Institut fu¨r Organische Chemie der RWTH Aachen, Landoltweg 1,
D-52074 Aachen, Germany
carsten.bolm@oc.rwth-aachen.de
Received February 4, 2005
ABSTRACT
Various ferrocene-based organosilanols have been synthesized in four steps starting from achiral ferrocene carboxylic acid. Applying these
novel planar-chiral ferrocenes as catalysts in asymmetric phenyl transfer reactions to substituted benzaldehydes afforded products with high
enantiomeric excesses. The best result (91% ee) was achieved in the addition to p-chlorobenzaldehyde with organosilanol 2b, which has a
tert-butyl substituent on the oxazoline ring and an isopropyl group on the silanol fragment.
Organosilanols have found important applications in various
fields,1 especially in the production of silicon-based poly-
meric materials.2 In organic synthesis they have been used in
palladium-catalyzed cross-coupling reactions3 and as anchor-
ing elements for ortho-metalation directors, for example.4
Furthermore, several organosilanols showed bioactivity,5 and
some of them were applied as structural components in
transition-state analogues of metalloprotease inhibitors.6 To
the best of our knowledge, however, they have never been
utilized as chiral ligands in catalytic asymmetric reactions.7
On the other hand, it is well-established that 1,2-disub-
stituted ferrocenes are very useful as versatile chiral ligands
in asymmetric metal catalysis.8 Following Ugi’s pioneering
work in 1970,9 they are commonly prepared starting from
monosubstituted ferrocenes by ortho-lithiation10 with direct-
ing groups such as amines and hydrazones,11 sulfoxides,12
acetals,13 or oxazolines14 and subsequent trapping of the
resulting lithium reagent with an appropriate electrophile.
(6) (a) Mutahi, wa M.; Nittoli, T.; Guo, L.; Sieburth, S. McN. J. Am.
Chem. Soc. 2002, 124, 7363. (b) Kim, J.; Sieburth, S. McN. J. Org. Chem.
2004, 69, 3008.
(7) For examples of silanols in achiral metal complexes, see: Malisch,
W.; Hofmann, M.; Voegler, M.; Schumacher, D.; Sohns, A.; Bera, H.; Jehle,
H. Silicon Chem. 2003, 348 and references therein.
(1) (a) Hirabayashi, K.; Mori, A. J. Synth. Org. Chem. Jpn. 2000, 58,
926. (b) For the synthesis amd structure of organosilanols, see: Chan-
drasekhar, V.; Boomishankar, R.; Nagendran, S. Chem. ReV. 2004, 104,
5847.
(2) Lickiss, P. D. AdV. Inorg. Chem. 1995, 42, 147.
(8) (a) Ferrocenes, Homogeneous Catalysis, Organic Synthesis, Material
Science; Togni, A., Hayashi, T., Eds.; VCH: Weinheim, 1995. (b)
Metallocenes; Togni, A., Halterman, R. L., Eds.; VCH: Weinheim, 1998.
(c) Dai, L. X.; Tu, T.; You, S. L.; Deng, W. P.; Hou, X. L. Acc. Chem.
Res. 2003, 36, 659. (d) Colacot, T. J. Chem. ReV. 2003, 103, 3101. (e)
Atkinson, R. C. J.; Gibson, V. C.; Long, N. J. Chem. Soc. ReV. 2004, 33,
313.
(3) (a) Hirabayashi, K.; Mori, A.; Kawashima, J.; Suguro, M.; Nishihara,
Y.; Hiyama, T. J. Org. Chem. 2000, 65, 5342. (b) Chang, S.; Yang, S. H.;
Lee, P. H. Tetrahedron Lett. 2001, 42, 4883. (c) Denmark, S. E.; Sweis, R.
F. Acc. Chem. Res. 2002, 35, 835. (d) Denmark, S. E.; Baird, J. D. Org.
Lett. 2004, 6, 3649. (e) Denmark, S. E.; Ober, M. H. AdV. Synth. Catal.
2004, 346, 1703 and references therein. (f) For conjugate additions, see:
Mori, A.; Danda, Y.; Fujii, T.; Hirabayashi, K.; Osakada, K. J. Am. Chem.
Soc. 2001, 123, 10774.
(9) Marquarding, D.; Klusacek, H.; Gokel, G.; Hoffmann, P.; Ugi, I. J.
Am. Chem. Soc. 1970, 92, 5389.
(4) Sieburth, M. C.; Fensterbank, L. J. Org. Chem. 1993, 58, 6314.
(5) For muscarinic antagonists, see: (a) Tacke, R.; Mahner, K.; Stro-
hmann, C.; Forth, B.; Mutschler, E.; Friebe, T.; Lambrecht, G. J. Organomet.
Chem. 1991, 417, 339. (b) Tacke, R.; Forth, B.; Waelbroeck, M.; Gross, J.;
Mutschler, E.; Lambrecht, G. J. Organomet. Chem. 1995, 505, 73. (c) Tacke,
R.; Heinrich, T.; Bertermann, R.; Burschka, C.; Hamacher, A.; Kassack,
M. U. Organometallics 2004, 23, 4468. (d) Daiss, J. O.; Penka, M.;
Burschka, C.; Tacke, R. Organometallics 2004, 23, 4987. Pheromone: (e)
Tacke, R.; Schmid, T.; Hofmann, M.; Tolasch, T.; Franke, W. Organome-
tallics 2003, 22, 370.
(10) For a recent review illustrating the major advances in directed
lithiations (by complex induced proximity effects), see: Whisler, M. C.;
MacNeil, S.; Snoeckus, V.; Beak, P. Angew. Chem., Int. Ed. 2004, 43,
2206.
(11) (a) Ganter, C.; Wagner, T. Chem. Ber. 1995, 128, 1157. (b) For the
use of chiral hydrazones, see: Enders, D.; Peter, R.; Lochtmann, R.;
Runsink, J. Eur. J. Org. Chem. 2000, 2839. (c) Review: Job, A.; Janeck,
C. F.; Bettray, W.; Peters, R.; Enders, D. Tetrahedron 2002, 58, 2253.
(12) Riant, O.; Argouarch, G.; Guillaneux, D.; Samuel, O.; Kagan, H.
B. J. Org. Chem. 1998, 63, 3511.
10.1021/ol050242+ CCC: $30.25
© 2005 American Chemical Society
Published on Web 03/10/2005

column chromatography and isolation of the major diaste-
reomer, stereochemically homogeneous samples of 2 were
obtained in 43-91% yield (Table 1). Most of the ferrocenyl
Table 1. Synthesis of Planar-Chiral Ferrocene-Based
Organosilanols 2
Figure 1.
Recently, we have demonstrated that ortho-substituted
ferrocene 1 (Figure 1) with oxazolinyl- and diphenylhydroxy
methyl groups is an effective catalyst for the asymmetric
aryl transfer reaction to aldehydes leading to products with
up to 99% ee.15 Motivated by those results, we wondered
about the applicability of structurally analogous organosil-
anols 2. Those compounds have the same oxazolinyl-
substituted ferrocene backbone but differ in the hydroxyl-
bearing side chain.16 The resulting steric and electronic modi-
fication was expected to have an impact on the examined
catalyst system and alter its activity and selectivity.17,18
entry
R′
R
compd (yield, %)a compound (yield, %)b
1
2
3
4
5
6
7
8
9
t-Bu
t-Bu
t-Bu
Ph
Ph
i-Pr
i-Pr
CH3
i-Pr
Ph
i-Pr
Ph
5a (64)
5b (64)
5c (91)
5d (70)
5e (68)
5f (81)
5g (85)
5h (82)
5i (60)
2a (91)c
2b (75)d
2c (77)d
2d (57)d
2e (53)d
2f (65)c
2g (72)c
2h (45)c
2i (43)c
Organosilanols 2 were prepared in two steps, starting from
chiral ferrocenyl oxazolines 4, which were readily available
from ferrocene carboxylic acid (3) following known literature
protocols.14 Subsequent diastereoselective ortho-lithiations
of ferrocenyl oxazolines 2 with s-BuLi at -78 °C in THF,14a
followed by electrophilic attack with various chlorosilanes,
gave diastereomerically enriched 1,2-disubstituted ferrocenes
5 in good yields (60-91%).19
i-Pr
Ph
CH2Ph i-Pr
CH2Ph Ph
a See comment in ref 19. b Yields of diastereomerically pure products.
c Reaction was performed at room temperature. d Reaction was performed
at 60 °C.
Using a method recently introduced by Chang and co-
workers,20 the silyl group of 5 was oxidized in air with [IrCl-
(C8H12)]2 as catalyst giving ferrocenyl organosilanols 2. After
organosilanols 2 were solid, air-stable compounds, which
could be stored for weeks without any indication of
decomposition.
The catalytic properties of organosilanols 2 were explored
in asymmetric phenyl-transfer reactions from organozinc
reagents to benzaldehydes 6 giving diarylmethanols 7.21 The
results are summarized in Table 2.
Initially, mixtures of diphenyl- and diethylzinc were used
as phenyl source and p-chlorobenzaldehyde (6a) as substrate.
Most organosilanols showed good enantioselectivities (up
to 91% ee) and afforded product 7a in respectable yields
(40-87%). The best result was obtained with organosilanol
2b, which had a tert-butyl substituent on the oxazoline ring
and isopropyl groups on the silanol fragment (Table 2, entry
2). Catalysts with methyl or phenyl substituents on the silicon
(13) Riant, O.; Samuel, O.; Flessner, T.; Taudien, S.; Kagan, H. B. J.
Org. Chem. 1997, 62, 6733.
(14) Some related examples: (a) Sammaika, T.; Latham, H. A.; Schaad,
D. R. J. Org. Chem. 1995, 60, 10. (b) Richards, C. J.; Damalidis, T.; Hibbs,
D. E.; Hursthouse, M. B. Synlett 1995, 74. (b) Sammaika, T.; Latham, H.
A. J. Org. Chem. 1996, 61, 1629. (c) Richards, C. J.; Mulvaney, A. W.
Tetrahedron: Asymmetry 1996, 7, 1419. (d) Nishibayashi, Y.; Uemura, S.
Synlett 1995, 79. (e) Bolm, C.; Muniz, K.; Seger, A.; Raabe, G. Synlett
1997, 1051. (f) Bolm, C.; Mun˜iz-Ferna´ndez, K.; Seger, A.; Raabe, G.;
Gu¨nther, K. J. Org. Chem. 1998, 63, 7860.
(15) (a) Bolm, C.; Mun˜iz, K. Chem. Commun. 1999, 1295. (b) Bolm,
C.; Hermanns, N.; Hildebrand, J. P.; Mun˜iz, K. Angew. Chem., Int. Ed.
2000, 39, 3465. (c) Bolm, C.; Hildebrand, J. P.; Muniz, K.; Hermanns, N.
Angew. Chem., Int. Ed.. 2001, 40, 3284. (d) Bolm, C.; Rudolph, J. J. Am.
Chem. Soc. 2002, 124, 14850. (e) Rudolph, J.; Hermanns, N.; Bolm, C. J.
Org. Chem. 2004, 69, 3997.
(16) For the synthesis and catalytic use of a structurally related planar-
chiral ferrocene with a selenium substituent, see: Bolm, C.; Kesselgruber,
M.; Grenz, A.; Hermanns, N.; Hildebrand, J. P. New J. Chem. 2001, 25,
13.
(17) For catalyzed asymmetric aryl-transfer reactions with other ligand
types, see: (a) Ko, D.-H.; Kim, K. H.; Ha, D.-C. Org. Lett. 2002, 4, 3759.
(b) Fontes, M.; Verdagner, X.; Sola`, L.; Perica`s, M. A.; Riera, A. J. Org.
Chem. 2004, 69, 2532. (c) Ji, J.-X.; Wu, J.; Au-Yeung, T. T.-L.; Yip,
C.-W.; Haynes, R. K.; Chan, A. S. C. J. Org. Chem. 2005, 70, 1093.
(18) Theoretical investigations: (a) Rudolph, J.; Rasmussen, T.; Bolm,
C.; Norrby, P.-O. Angew. Chem., Int. Ed. 2003, 40, 3002. (b) Rudolph, J.;
Norrby, P.-O.; Bolm, C. J. Am. Chem. Soc. 2005, 127, 1548.
(19) When the diastereomer ratio (commonly >90% de) was determined
by 1H NMR spectroscopy of the crude product mixture, it was found to be
consistent with comparable literature data (cf. ref 14a). Ferrocenyl deriva-
tives 5 having Si-H bonds proved to be rather unstable, and thus, the crude
products were converted into their oxidized analogues 2 without extensive
purification. The given yields should therefore be considered as “crude
yields” of rapidly purified products.
(20) (a) Lee, Y.; Seomoon, D.; Kim, S.; Han, H.; Chang, S.; Lee, P. H.
J. Org. Chem. 2004, 69, 1741. (b) Na, Y.; Lee, C.; Pak, J. Y.; Lee, K. H.;
Chang, S. Tetrahedron Lett. 2004, 45, 7863.
(21) Diarylmethanols are important intermediates for the synthesis of
biologically active and pharmaceutically relevant substances. For a selection
of references, see: (a) Meguro, K.; Aizawa, M.; Sohda, T.; Kawamatsu,
Y.; Nagaoka, A. Chem. Pharm. Bull. 1985, 33, 3787. (b) Toda, F.; Tanaka,
K.; Koshiro, K. Tetrahedron: Asymmetry 1991, 2, 873. (c) Stanev, S.;
Rakovska, R.; Berova, N.; Snatzke, G. Tetrahedron: Asymmetry 1995, 6,
183. (d) Botta, M.; Summa, V.; Corelli, F.; Di Pietro, G.; Lombardi, P.
Tetrahedron: Asymmetry 1996, 7, 1263. (e) Bolshan, Y.; Chen, C.-Y.;
Chilenski, J. R.; Gosselin, F.; Mathre, D. J.; O’Shea, P. D.; Roy, A.; Tillyer,
R. D. Org. Lett. 2004, 6, 111.
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Org. Lett., Vol. 7, No. 7, 2005

When the tert-butyl group on the oxazoline was substituted
by a phenyl, an isopropyl, or a benzyl substituent giving
organosilanols 2d,e, 2f,g, and 2h,i, respectively, the resulting
catalysts were less enantioselective (Table 2, entries 4-9).24
Using triphenylborane (method B, Table 2, entry 10)25
instead of diphenylzinc as aryl source (in combination with
a catalyst derived from 2c) had only a minor effect on the
ee of the aryl-transfer reaction. With phenylboronic acid
(method C, Table 2, entry 11)15d,e,17c,26 both yield and ee were
lower.
Table 2. Asymmetric Phenyl Transfer Reaction to Substituted
Benzaldehydes (6) Using Organosilanol-Based Catalysts and
Various Zinc Reagentsa
methodb
(product)
yieldc
(%)
eed
(%)
Other aryl aldehydes reacted well too as demonstrated in
catalyses with organosilanol 2c (Table 2, entries 12-14).
For example, 4-methoxybenzaldehyde afforded the corre-
sponding product (7b) with 87% ee in 81% yield. A
remarkable enantioselectivity was also observed in the phenyl
addition to o-bromobenzaldehyde, which gave 7c with 84%
ee in 70% yield.
In summary, we have described the synthesis of planar-
chiral ferrocene-based organosilanols 2 and demonstrated
their catalytic use in asymmetric phenyl-transfer reactions
to substituted benzaldehydes. High enantioselectivities and
yields of up to 91 and 87%, respectively, have been achieved
using both zinc- and boron-based aryl sources. To the best
of our knowledge, this is the first application of chiral
organosilanols in asymmetric catalysis, and we are currently
exploring the potential use of this new ligand class in other
enantioselective reactions.
entry
substrate
organosilanol
1
2
3
4
5
6
7
8
9
10
11
12
13
14
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
6c
6d
2a
2b
2c
2d
2e
2f
2g
2h
2i
2c
2c
2c
2c
2c
A (7a)
A (7a)
A (7a)
A (7a)
A (7a)
A (7a)
A (7a)
A (7a)
A (7a)
B (7a)
C (7a)
A (7b)
A (7c)
A (7d)
40
82
84
82
76
87
73
85
nde
73
67
81
70
84
30
91
89
87
85
78
76
63
58
88
83
87
84
83
a All reactions were run on a 0.25 mmol scale using 10 mol % of 2.
b Method A: use of Ph2Zn (0.65 equiv) and Et2Zn (1.3 equiv) in toluene at
10 °C for 12 h. Method B: use of BPh3 (1.0 equiv) and Et2Zn (3.0 equiv)
at 10 °C for 12 h. Method C: use of PhB(OH)2, (2.4 equiv), Et2Zn (7.2
equiv), and DiMPEG (10 mol %; MW ) 2000 g‚mol-1) in toluene (first at
60 °C for 12 h, then at 10 °C for 12 h). c After column chromatography.
d Enantiomeric ratios were determind by HPLC analysis using a chiral
column. The major product had R configuration. e Not determined.
Acknowledgment. We are grateful to the Fonds der
Chemischen Industrie and the Deutsche Forschungsgemein-
schaft (DFG) within the SFB 380 and the GRK 440 for
financial support. We also thank Degussa AG, Bayer AG,
and Crompton Corp. (previously Witco) for the donation of
chemicals. Jens Rudolph is acknowledged for additional
studies and discussions.
atom (entries 1 and 3) led to products with lower ee values
(7a with 30 and 89% ee for 2a and 2c, respectively). In light
of our previous results,14e,f,15,16,22 this observation is rather
remarkable, since until now achieving high enantioselectivi-
ties in the aryl-transfer reactions always required the presents
of the “magic” diphenylhydroxymethyl unit23 in the 2
position of planar-chiral metallocenes.
Supporting Information Available: Experimental pro-
cedures and full characterization (1H and 13C NMR data and
spectra, MS, IR, and CHN analyses) for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL050242+
(22) (a) Bolm, C.; Kesselgruber, M.; Hermanns, N.; Hildebrand, J. P.
Angew. Chem., Int. Ed. 2001, 40, 1488. (b) Bolm, C.; Hermanns, N.;
Kesselgruber, M.; Hildebrand, J. P. J. Organomet. Chem. 2001, 624, 157.
(c) Bolm, C.; Hermanns, N.; Classen, A.; Mun˜iz, K. Bioorg. Med. Chem.
Lett. 2002, 12, 1795. (d) Bolm, C.; Mun˜iz, K.; Hildebrand, J. P. Org. Lett.
1999, 1, 491.
(23) (a) Braun, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 519. (b) Beck,
A. K.; Bastani, B.; Plattner, D. A.; Petter, W.; Seebach, D.; Braunschweiger,
H.; Gysi, P.; LaVecchia, L. Chimia 1991, 45, 238. (c) Seebach, D.; Beck,
A. K.; Heckel, A. Angew. Chem., Int. Ed. 2001, 40, 92 and references
therein.
(24) Assuming that a combination of sterically bulky substituents at the
oxazoline ring and the silanol fragment in 2 would lead to even higher
enantioselectivities in the aryl transfer reaction, we also tried to prepare
organosilanols with tert-butyl groups at the silicon atom. Those attempts,
however, remained unsuccessful, since lithiated oxazolines 4 did not react
with di-tert-butylchlorosilane.
(25) Rudolph, J.; Schmidt, F.; Bolm, C. AdV. Synth. Catal. 2004, 346,
867.
(26) Rudolph, J.; Schmidt, F.; Bolm, C. Synthesis 2005, published online
http://dx.doi.org/10.1055/s-2004-834887.
Org. Lett., Vol. 7, No. 7, 2005
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