C O M M U N I C A T I O N S
Table 2. Asymmetric Ring Opening of meso-Epoxidesa
cance of this conformation is not clear, however, as the bisphosphine
oxide appears to be C2-symmetric on the NMR time scale.
We initiated our studies of catalysis by considering the asymmetric
addition of SiCl4 to meso-epoxides. The Denmark group demonstrated
that optically active phosphorus triamides could catalyze this trans-
formation;13 subsequent reports revealed the utility of pyridine N-oxides
and phosphine oxides.14 Mechanistically, these reactions are thought
to involve coordination of one or more Lewis bases to SiCl4 to generate
a more Lewis acidic species (LB)nSiCl3+ (LB ) Lewis base) capable
of activating the epoxide toward ring opening.13b
entry
R
3d (mol %)
yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13
Phd (4a)
4-F-Ph (4b)
4-CH3-Ph (4c)
4-CF3-Ph (4d)
4-Cl-Ph (4e)
3-CH3-Ph (4f)
3-Cl-Ph (4g)
3-CF3-Ph (4h)
3-CH3O-Ph (4i)
2-Br-Ph (4j)
BnOCH2 (4k)
(CH2)4 (4l)
0.1
0.1
0.1
2
0.1
0.2
2
2
0.2
2
97
96
92
97
89
89
96
91
95
<5
90
95
76
94
93
89
87
82
91
90
88
88
---
60
29
50
i
cis-Stilbene oxide was exposed to SiCl4 and Pr2NEt in the
presence of catalytic allene-containing mono- or bisphosphine
oxides 3 (AllenePO, Table 1). These experiments revealed several
aspects of the ring-opening reaction: (1) Allene-containing ligands
can induce enantioselectivity in catalytic reactions. (2) In general,
bisphosphine oxides (e.g, 3b) displayed higher reactivities and
enantioselectivities than the monophosphine oxide (3a). (3) Sub-
stantial variation on the allene itself was tolerated, as both the
methyl- and phenyl-substituted catalysts (3c, 3d) were reactive and
enantioselective. (4) The ring opening is sensitive to the aryl rings
on the phosphine oxide. Both electron-donating groups (entries 6
and 8) and, more profoundly, electron-withdrawing groups (entries
7 and 9) decreased the reactivity and, where measurable, the
selectivity. (5) The diphenyl-substituted catalyst 3d is a highly
reactiVe and enantioselectiVe catalyst, displaying nearly 1000
turnoVers and generating the chlorohydrin in 94% ee (entry 10).
2
0.1
0.1
exo-2,3-norbornyl (4m)
a All of the reactions were quenched with propylene oxide and KF/
KH2PO4 buffer. See the Supporting Information for details. b Isolated
yields. c For entries 1-12, the ee was determined by HPLC; for entry
13, the ee was determined by GC. d Ph ) phenyl.
we could recover catalyst 3d in 94% yield from a reaction involving
the ring opening of epoxide 4a.11
More than a century after van’t Hoff recognized that allenes could
be chiral, we have demonstrated that their chirality can be harnessed
in the service of asymmetric catalysis. In the present example, we have
prepared organic Lewis bases and shown that they can activate SiCl4.
However, this design principle may extend equally well to other classes
of organic catalysts or ligands for transition metals.7 The utility of
allenes in these contexts is the subject of current investigations.
Table 1. Evaluation of Phosphine Oxides as Catalysts for the
Addition of SiCl4 to cis-Stilbene Oxidea
Acknowledgment. X-ray crystallography was performed by
Vincent Lynch (UT Austin) and Radha Akella (UTSW). We are
grateful to the NIGMS (R01-GM074822), the Welch Foundation,
and Amgen. J.M.R. is a fellow of the Alfred P. Sloan Foundation.
entry
AllenePO
loading (mol %)
% yield
% eeb (+/-)
1
2
3
4
5
6
7
8
3ac
3ac
3bd
3c
3d
3e
10
2
2
2
2
2
2
2
2
39
<10
47
76
93
86
<5
58
<10
---
54 (-)
84 (-)
89 (+)
84 (+)
---
78 (+)
---
94 (+)
Supporting Information Available: Complete experimental details
and characterization data, including CIF files. This material is available
3f
3g
3h
3d
References
9
<5
97
(1) ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yama-
moto, H., Eds.; Springer-Verlag: Berlin, 1999.
(2) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346.
10e
0.1
a Reactions were carried out with [4a] ) 0.02 M unless otherwise
noted. b Determined by HPLC. c 3a was 70% ee. d 3b was 79% ee.
e [4a] ) 0.2 M.
(3) For the use of axially chiral ligands based on a spirodiindane backbone,
see: Fu, Y.; Xie, J.-H.; Hu, A.-G.; Zhao, H.; Wang, L.-X.; Zhou, Q.-L.
Chem. Commun. 2002, 480.
(4) van’t Hoff, J. H. The Arrangement of Atoms in Space; Eiloart, A., Transl.;
Green and Co.: London, 1898; pp 103-104.
A set of meso-epoxides were opened with SiCl4 in the presence
of catalyst 3d (Table 2). In general, the reaction is effective for
substituted stilbene oxides. Both electron-releasing and electron-
withdrawing substituents are tolerated in the meta or para position,
although the electron-poor substrates tended to require increased
catalyst loadings (entries 4, 7, 8). In contrast, ortho-substituted
stilbene oxides were not reactive (entry 10). Finally, the chloro-
hydrins derived from linear, cyclic, or bicyclic aliphatic epoxides
were isolated in high yield but with rather unimpressive enantio-
meric excesses (entries 11-13).
Allenes have attracted attention from the synthetic community
because, among other reasons, they react with both nucleophiles
and electrophiles, often under mild conditions. In the present
circumstance, however, this reactivity profile represented a potential
liability inasmuch as catalyst stability would be critical for a
practical synthetic method. In this regard, we were encouraged that
(5) Sato, I.; Matsueda, Y.; Kadowaki, K.; Yonekubo, S.; Shibata, T.; Soai, K.
HelV. Chim. Acta 2002, 85, 3383.
(6) Kawasaki, T.; Sato, M.; Ishiguro, S.; Takahiro, S.; Yosuke, M.; Sato, I.;
Nishino, H.; Inoue, Y.; Soai, K. J. Am. Chem. Soc. 2005, 127, 3274.
(7) Krause and co-workers reported an allene-containing (bispyridine)Ag+
complex, although no catalysis was demonstrated: Lohr, S.; Averbeck, J.;
Schurmann, M.; Krause, N. Eur. J. Inorg. Chem. 2008, 552.
(8) Denmark, S. E.; Beutner, G. L. Angew. Chem., Int. Ed. 2008, 47, 1560.
(9) Cozzi, P. G.; Alesi, S. Chem. Commun. 2004, 2448.
(10) Toda, F.; Tanaka, K. Tetrahedron. Lett. 1981, 22, 4669.
(11) See the Supporting Information for details.
(12) 3a and 3b were prepared and used in 70 and 79% ee, respectively.
(13) (a) Denmark, S. E.; Barsanti, P. A.; Wong, K.-T.; Stavenger, R. A. J. Org.
Chem. 1998, 63, 2428. (b) Denmark, S. E.; Barsanti, P. A.; Beutner, G. L.;
Wilson, T. W. AdV. Synth. Catal. 2007, 348, 567.
(14) (a) Tao, B.; Lo, M. M.-C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 353.
(b) Nakajima, M.; Saito, M.; Uemura, M.; Hashimoto, S. Tetrahedron Lett.
2002, 43, 8827. (c) Tokuoka, E.; Kotani, S.; Matsunaga, H.; Ishizuka, T.;
Hashimoto, S.; Nakajima, M. Tetrahedron: Asymmetry 2005, 16, 2391.
(d) Takenaka, N.; Sarangthem, R. S.; Captain, B. Angew. Chem., Int. Ed.
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