C O M M U N I C A T I O N S
Table 2. Intramolecular Cyclopropanation of Mesityl Sulfones
3c-f
isopropyl group and also with the benzyl group of the ligand, with
steric repulsion. As a result, the si-face will be sterically hindered
during the cyclopropanation reactions. By contrast, the reaction at
the re-face would be preferred because the unfavorable interactions
with the aryl sulfonyl group would be negligible in the transition
states arising from models A and B. Thus, the aryl sulfonyl group
has a crucial role in the enantioselection. The high enantioselec-
tivities obtained for the mesityl sulfones are also well explained
by the increased unfavorable interactions with the mesityl group.
The reversal of enantioselection for 3e, 5a, and 5b would be
rationalized by model B because the steric strain with the substrates
would disfavor model A. The depicted orientation of the alkene
with respect to the re-face of the complex well explains the (1R,
5R) configuration for 4e, and the (1S, 5R, 6R, 7S) configuration
for 6a and 6b.
For 7a and 7b, model A would operate. As the steric strain with
the substrate is so large in this case, the use of a less bulky phenyl
sulfone might be sufficient for high enantioselectivity.
In summary, highly enantioselective asymmetric catalysis on the
intramolecular cyclopropanation of R-diazo-â-keto sulfones has
been developed. The products possess great potential for natural
product synthesis because (1) a variety of chemistries of cyclo-
propane, ketone, and sulfone are available, and (2) the products
are highly crystalline, facilitating the production of enantiomerically
pure synthetic intermediates.
entry product
ligand
ee (%)a,b
yield (%)c
temp (°C)
time (h)
1
2
3
4
4c
4c
4c
4c
2a
2b
2d
2e
81 (1R)
69 (1R)
87 (1R)
98 (1R)
96
98
94
90
50
1
rt, 50d
rt, 50d
50
2, 2.5d
2, 1.5d
2
5
6
7
8
4d
4d
4d
4d
2a
2b
2d
2e
92 (1S)
56 (1S)
95 (1S)
98 (1S)
68
44
43
63
50
50
50
50
1
1.5
1.5
2.5
9
10
11
12
4e
4e
4e
4e
2a
2b
2d
2e
74 (1R)e,f
71 (1R)e,f
76 (1R)e,f
92 (1R)e,f
74
77
54
84
50
50
50
rt
1.5
0.5
2
5
13
14
15
16
4f
4f
4f
4f
2a
2b
2d
2e
78 (1R)
73 (1R)
84 (1R)
91 (1R)
91
96
75
98
rt, 50, 70d 1.5, 12, 10d
50, 70d
10, 20d
rt, 50, 70d 3.5, 13, 5d
rt, 50, 70d 3.5, 13, 7d
a-d See the footnotes to Table 1. e The absolute structure is the opposite
of the depicted structure above. f CuOTf (20 mol %) and ligand (30 mol
%) were used because the reaction was sluggish.
Acknowledgment. We thank Messrs Kenji Namoto and Koichi
Yonezawa for early experiments, and Dr. M. Shiro of Rigaku for
assistance with X-ray crystallography. This work was financially
supported in part by 21COE “Practical Nano-Chemistry”.
Table 3. Enantioselective Formation of the Tricyclic Compounds
Supporting Information Available: Experimental details and
characterization data for all new compounds (PDF). An X-ray crystal-
lographic file is available in CIF format. This material is available free
References
entry
product
ligand
ee (%)a,b
yield (%)c
temp (°C)
time (h)
(1) Nozaki, H.; Takaya, H.; Moriuti, S.; Noyori, R. Tetrahedron 1968, 24,
3655-3658.
1
2
3
4
6a
6a
6b
6b
2a
2e
2a
2e
33 (7S)e
66 (7S)e
79 (7S)e
93 (7S)e
quant.
81
76
rt
rt
0.5
5
(2) Reviews: (a) Davies, H. M. L. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, Chapter 4.8,
pp 1031-1067. (b) Doyle, M. P.; Protopopova, M. N. Tetrahedron 1998,
54, 7919-7946 and references therein. (c) Doyle, M. P. In Catalytic
Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; YHC Publishers: New
York, 2000; Chapter 5, pp 191-228 and references therein.
(3) Recent studies for R-diazo ketones: (a) Barberis, M.; Pe´rez-Prieto, J.;
Herbst, K.; Lahuerta, P. Organometallics 2002, 21, 1667-1673. (b)
Barberis, M.; Perez-Prieto, J.; Stiriba, S.-E.; Lahuerta, P. Org. Lett. 2001,
3, 3317-3319. (c) Park, S. W.; Son, J. H.; Kim, S. G.; Ahn, K. H.
Tetrahedron: Asymmetry 1999, 10, 1903-1911. (d) Kim, S. G.; Cho, C.
W.; Ahn, K. H. Tetrahedron 1999, 55, 10079-10086.
rt, 50d
rt, 50d
2, 20d
1, 27d
61
5
6
7
8
8a
8a
8b
8b
2a
2e
2a
2e
92 (7R)
90 (7R)
97 (7R)
87 (7R)
78
37
69
7
rt
3.5
rt, 50d
rt
1, 2d
27
rt, 50d
1, 29d
a-e See the footnotes to Table 1.
(4) (a) Dauben, W. G.; Hendricks, R. T.; Luzzio, M.; Ng, H. P. Tetrahedron
Lett. 1990, 48, 6969-6972. (b) Pique´, C.; Fa¨hndrich, B.; Pfaltz, A. Synlett
1995, 491-492. (c) Mu¨hler, P.; Bole´a, C. Synlett 2000, 6, 826-828. (d)
Mu¨hler, P.; Bole´a, C. HelV. Chim. Acta 2001, 84, 1093-1111.
(5) The same reaction condition of entry 1 in Table 1 was used. See Supporting
Information for the details.
(6) The highest ee observed for 4a was ca. 12% ee: Kennedy, M.; McKervey,
M. A.; Maguire, A. R.; Roos, G. H. P. J. Chem. Soc., Chem. Commun.
1990, 361-362.
(7) (a) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726-728. (b) Denmark, S. E.; Nakajima, N.;
Nicaise, O. J.-C.; Faucher, A.-M.; Edwards, J. P. J. Org. Chem. 1995,
60, 4884-4892. (c) von Matt, P.; Lloyd-Jones, G. C.; Minidis, A. B. E.;
Pfaltz, A.; Macko, L.; Neuburger, M.; Zehnder, M.; Rueegger, H.;
Pregosin, P. S. HelV. Chim. Acta 1995, 78, 265-284.
Figure 1. Proposed models A and B.
reactions would be well explained by the proposed models A and
B (Figure 1).9
(8) Solvents other than toluene afforded diminished enantioselectivities.
(9) Models A and B are depicted on the basis of Pfaltz’s model10 and the
recent theoretical analysis.11
The cyclopropanation reactions are thought to occur preferentially
at the re-face (defined by the CudC-C arrangement) of the chiral
catalyst-carbene complexes, because steric hindrance will be
encountered during cyclopropanation reactions at the si-face. That
is, if the olefin approaches from the si-face, the resultant pyramidal
conformation of the carbene C atom in the transition state9 means
that the aryl sulfonyl group will interact unfavorably with the
(10) (a) Fritschi, H.; Leutenegger, U.; Phaltz, A. HelV. Chim. Acta 1988, 71,
1553-1565. (b) Phaltz, A. In Modern Synthetic Methods 1989; Scheffold,
R., Ed.; Springer: Berlin-Heidelberg, 1989; pp 199-248.
(11) Fraile, J. M.; Garc´ıa, J. I.; Mart´ınes-Merino, V.; Mayoral, J. A.; Salvatella,
L. J. Am. Chem. Soc. 2001, 123, 7616-7625.
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