annulation partner (eqn (2)), presumably due to the ineffectiveness
of chloride anion as an activator of the silylindene.
ð2Þ
Fig. 2 ORTEP illustration, with thermal ellipsoids drawn at the 35%
probability level, of N-cinnamoylated (+)-2 (for the sake of clarity, the PF6
counterion and most of the hydrogens have been omitted).
positioned on the side of the upper cyclopentadienyl ring,
presumably for steric reasons. The a,b-unsaturated carbonyl
system lies in an s-cis conformation. The crystal structure suggests
that nucleophiles might prefer to add to the si face of the b carbon,
which is consistent with the stereochemistry that we observe in the
annulation process (cf. eqn (3)).
We have determined that an array of cinnamoyl fluorides and
related compounds may be used in this catalytic asymmetric
annulation process. Thus, electronically diverse (Table 1, entries
2–4), as well as ortho-substituted (entries 5 and 6; somewhat lower
yields are obtained), aryl substituents can be employed. In
addition, heteroaryl groups are tolerated in the b position
(entries 7 and 8).11
Thus, we have established that planar-chiral DMAP derivatives
catalyze intriguing [3 + 2] annulation reactions of silylated indenes
to produce diquinanes that bear three contiguous stereocenters
(one quaternary and two tertiary). We believe that this process
represents the first example of a mode of reactivity for these
DMAP derivatives wherein a transiently generated a,b-unsatu-
rated acylpyridinium ion (e.g., C) serves as an acceptor in a
stereoselective conjugate addition reaction. In future work, we will
exploit the utility of such intermediates in other catalytic
asymmetric processes.
Interestingly, this enantioselective [3 + 2] reaction can be applied
to annulations of unsymmetrical indenes. Thus, an isopropyl/
methyl-substituted substrate reacts to provide a 6 : 1 ratio of D : E
(eqn (3)).
Support has been provided by the NIH (National Institute of
ð3Þ
General
Medical
Sciences:
R01-GM57034),
Deutsche
Forschungsgemeinschaft (postdoctoral fellowship BA 2875/1-1 to
E.B.), Merck, and Novartis. We thank Luke Firmansjah and Dr
Richard J. Staples (Harvard University) for assistance with X-ray
crystallography. Funding for the MIT Department of Chemistry
Instrumentation Facility has been furnished in part by NSF CHE-
9808061 and NSF DBI-9729592.
We have obtained an X-ray crystal structure of the
N-cinnamoylated pyridinium salt derived from (+)-2§ (Fig. 2).12
The cinnamoyl group is essentially coplanar with the heterocycle,
allowing overlap between the p systems of these subunits. With
regard to the orientation around the N–C (carbonyl carbon) bond,
the carbonyl oxygen, rather than the larger alkenyl group, is
Notes and references
§ Crystallographic data for N-cinnamoylated (+)-2 (Fig. 2):
C31H35F6FeN2OP, formula weight: 652.43, tetragonal, P4(3)2(1)2, a =
3
˚
˚
˚
b = 11.9811(3) A, c = 40.4968(19) A, V = 5813.2(3) A , Z = 8, m =
0.641 mm21, reflections collected: 124357, independent reflections: 7504
[R(int) = 0.0955], final R indices [I > 2s(I)]: R1 = 0.0405, wR2 = 0.0862, R
indices (all data): R1 = 0.0501, wR2 = 0.0904.
Table 1 Catalytic asymmetric [3 + 2] annulations
Crystallographic data for the product of entry 4 of Table 1 (generated by
(+)-2): C20H17BrO, formula weight: 353.25, orthorhombic, P2(1)2(1)2(1),
3
˚
˚
˚
˚
a = 7.2277(14) A, b = 14.583(3) A, c = 15.656(3) A, V = 1650.2(5) A , Z =
4, m = 2.490 mm21, reflections collected: 9518, independent reflections:
3593 [R(int) = 0.0238], final R indices [I > 2s(I)]: R1 = 0.0328, wR2 =
0.0694, R indices (all data): R1 = 0.0437, wR2 = 0.0728. CCDC 294368 and
294369. For crystallographic data in CIF or other electronic format see
DOI: 10.1039/b603172b.
Entry
R
Yielda,b (%)
eea (%)
dra
1 B. L. Hodous, J. C. Ruble and G. C. Fu, J. Am. Chem. Soc., 1999, 121,
2637.
2 B. L. Hodous and G. C. Fu, J. Am. Chem. Soc., 2002, 124, 1578;
E. C. Lee, B. L. Hodous, E. Bergin, C. Shih and G. C. Fu, J. Am. Chem.
Soc., 2005, 127, 11586.
3 J. E. Wilson and G. C. Fu, Angew. Chem., Int. Ed., 2004, 43, 6358.
4 J. C. Ruble, H. A. Latham and G. C. Fu, J. Am. Chem. Soc., 1997, 119,
1492; B. Tao, J. C. Ruble, D. A. Hoic and G. C. Fu, J. Am. Chem. Soc.,
1999, 121, 5091; S. Arai, S. Bellemin-Laponnaz and G. C. Fu, Angew.
Chem., Int. Ed., 2001, 40, 234.
1
2
3
4
5
6
7
8
a
Ph
60
51
61
52
41
42
47
48
b
78
58
70
70
66
70
75
77
12 : 1
7 : 1
8 : 1
9 : 1
7 : 1
9 : 1
6 : 1
9 : 1
3-F–C6H4
3,5-(MeO)2C6H3
4-Br–C6H4
2-Me–C6H4
1-Naphthyl
2-Furyl
3-Furyl
Average of two experiments.
diastereomer.
Isolated yield of the major
5 J. C. Ruble and G. C. Fu, J. Am. Chem. Soc., 1998, 120, 11532;
I. D. Hills and G. C. Fu, Angew. Chem., Int. Ed., 2003, 42, 3921;
This journal is ß The Royal Society of Chemistry 2006
Chem. Commun., 2006, 2604–2606 | 2605