C O M M U N I C A T I O N S
Table 1. Aminocyclopentenonesa
It is interesting to note that, due to the constraints of the
intramolecular attack, the R carbon atom in 27 has the opposite
stereochemistry as for products in which the carbocation is trapped
in a bimolecular process.
In conclusion, we have demonstrated the first asymmetric version
of the amine-interrupted Nazarov cyclization process. This reaction
furnishes diastereomerically pure products. The success of the whole
process relies on the ease with which allenyl vinyl ketones undergo
the Nazarov cyclization in the presence of even the weakest acid
catalysts,4,9 the tolerance of the system to acid-labile functional
groups, and the isomerization of the propargyl vinyl ketones which
may result in formation of single axial isomers of the intermediate
allenyl ketones. This tandem process is likely to have utility in
total synthesis.10
Acknowledgment. Acknowledgment is made to the Department
of Defense Breast Cancer Research Program (DAMD17-03-1-0685)
and to the National Institutes of Health (GM57873) for generous
support.
a Enones were stirred with activated Florisil (ca. 6 g/mmol ketone) and
10 equiv of amine for 45 min. Yields are for cyclization of the propargyl
vinyl ketones.
Supporting Information Available: Complete experimental pro-
cedures for the preparation of 6, 20, and 27-29, analytical data, and
1H and 13C NMR for 6-29. This material is available free of charge
References
(1) (a) Tius, M. A. Acc. Chem. Res. 2003, 36, 284-290. For reviews of the
Nazarov reaction, see: (b) Habermas, K. L.; Denmark, S.; Jones, T. K.
In Organic Reactions; Paquette, L. A., Ed.; John Wiley & Sons, Inc.:
New York, 1994; Vol. 45, pp 1-158. (c) Harmata, M. Chemtracts 2004,
17, 416-435. (d) Frontier, A. J.; Collison, C. Tetrahedron 2005, 61,
7577-7606. (e) Pellissier, H. Tetrahedron 2005, 61, 6479-6517. (f) Tius,
M. A. Eur. J. Org. Chem. 2005, 2193-2206.
(2) Dhoro, F.; Tius, M. A. J. Am. Chem. Soc. 2005, 127, 12472-12473.
(3) (a) Harrington, P. E.; Murai, T.; Chu, C.; Tius, M. A. J. Am. Chem Soc.
2002, 124, 10091-10100. (b) The chiral auxiliary was prepared according
to a modified literature procedure (see Supporting Information).
(4) The crude product was purified by rapid chromatography on silica gel.
Long contact times with silica gel led to the formation of cyclic material.
See: (a) Forest, J.; Bee, C.; Cordaro, F.; Tius, M. A. Org. Lett. 2003, 5,
4069-4072. (b) Uhrich, E. A.; Batson, W. A.; Tius, M. A. Synthesis 2006,
2139-2142.
(5) (a) Bender, J. A.; Arif, A. M.; West, F. G. J. Am. Chem. Soc. 1999, 121,
7443-7444. (b) Browder, C. C.; Marmsa¨ter, F. P.; West, F. G. Org. Lett.
2001, 3, 3033-3035. (c) Yungai, A.; West, F. G. Tetrahedron Lett. 2004,
45, 5445-5448. (d) Bender, J. A.; Blize, A. E.; Browder, C. C.; Giese,
S.; West, F. G. J. Org. Chem. 1998, 63, 2430-2431. (e) Rostami, A.;
Wang, Y.; Arif, A. M.; McDonald, R.; West, F. G. Org. Lett. 2007, 9,
703-706. (f) White, T. D.; West, F. G. Tetrahedron Lett. 2005, 46, 5629-
5632.
Figure 2. Molecular diagram of the picrate salt of 20 with thermal ellipsoids
shown at 30% probability. Quaternary amine hydrogen atom H1 depicted
with arbitrary radius. All other hydrogen atoms are omitted for clarity.
Orthorhombic; P212121; a ) 12.583(4), b ) 16.903(6), c ) 19.953(7) Å;
wR ) 4.95%; CCDC 639752.
(6) Mariella, P. R.; Gruber, J. M.; Elder, J. W. S. J. Org. Chem. 1961, 26
3217-3221.
(7) Li, H.; Yang, J.; Porter, N. A. Photochem. Photobiol. A: Chem. 2005,
169, 289-297.
(8) The methyl protons in 27 showed a positive nOe with the benzylic proton.
(9) Tius, M. A.; Busch-Petersen, J.; Yamashita, M. Tetrahedron Lett. 1998,
39, 4219-4222.
Exposure of this sensitive aminoketone to activated Florisil (ca. 6
g/mmol ketone) and 10 equiv of triethylamine in the absence of
solvent and with vigorous agitation gave indoline 27 in 50% overall
yield from 25. The stereochemistry that is shown8 reflects the
preferred sense of conrotatory ring closure followed by intramo-
lecular trapping of the intermediate carbocation (cf. 8, Scheme 2).
(10) The TIPS group and chiral auxiliary are easily cleaved from the products.
Exposure of 23 to tetra-n-butylammonium fluoride in THF led to rapid
cleavage of the TIPS group (28, 92% yield). Subsequent exposure of the
product to chlorotrimethylsilane in methanol at 0 °C led to cleavage of
the chiral auxiliary (29, 93% yield). See the Supporting Information for
details.
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