Asymmetric synthesis of cis-fused bicyclic pyrrolidines and pyrrolidinones via chiral polycyclic lactams

Journal of Organic Chemistry

Volumn 61, Issue 17, 1996, Pages 5813-5817

  Ennis, Michael D ^a   Hoffman, Robert L ^a   Ghazal, Nabil B ^a   Old, David W ^a   Mooney, Pamela A ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BICYCLO[3.3.0]OCTANE DERIVATIVE; LACTAM DERIVATIVE; PYRROLIDINE DERIVATIVE; SEROTONIN AGONIST; U 93385; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; GAS CHROMATOGRAPHY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029823172     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo960185l     Document Type: Article

References (22)

1. (a) Meyers, A. I.; Romo, D. Tetrahedron 1991, 47, 9503-9569.
2. (b) Meyers, A. I.; Lefker, B. A. Tetrahedron 1987, 43, 5663-5676.
3. (a) Meyers, A. I.; Burgess, L. E. J. Org. Chem. 1991, 56, 2294-2296.
4. (b) Burgess, L. E.; Meyers, A. I. J. Am. Chem. Soc. 1991, 113, 9858-9859.
5. (c) Burgess, L. E.; Meyers, A. I. J. Org. Chem. 1992, 57, 1656-1662.
6. (d) Meyers, A. I.; Snyder, L. J. Org. Chem. 1992, 57, 3814-3819.
7. (e) Westrum, L. J.; Meyers, A. I. Tetrahedron Lett. 1994, 35, 973-976.
8. (f) Tschantz, M. A.; Burgess, L. E.; Meyers, A. I. Org. Synth. 1994, 73, 221-230.
9. (g) Bienz, S.; Busacca, C.; Meyers, A. I. J. Am. Chem. Soc. 1989, 111, 1905-1907.
10. Munchhof, M. J.; Meyers, A. I. J. Org. Chem. 1995, 60, 7084-7085.
11. See Denmark, S. E.; Marcin, L. R. J. Org. Chem. 1995, 60, 3221-3235 for an excellent overview of the enantioselective synthesis of substituted pyrrolidines.
12. Lin, C.-H.; Haadsma-Svensson, S. R.; Phillips, G.; McCall, R. B.; Piercey, M. F.; Smith, M. W.; Svensson, K.; Carlsson, A.; Chidester, C. G.; VonVoigtlander, P. F. J. Med. Chem. 1993, 36, 2208-2218.
13. 13C NMR (75.5 MHz), IR, and possess satisfactory elemental analysis.
14. 3OD is treated with a catalytic amount of p-TsOH (0.1 equiv) at room temperature, one observes a gradual diminution of the benzylic proton resonance. While it is possible that iminium ion B is in equilibrium with ii whereas A is not, we have no evidence to suggest that. equation presented
15. The scale-up of this condensation was carried out by Dr. Thomas A. Runge, Chemical Research Preparations, Pharmacia and Upjohn, Inc.
16. Meyers has also observed that using LAH alone is less clean than using alane for these reductions (see ref 2a).
17. We chose to protect the primary hydroxyl of 4 as a benzyl for convenience and cost reasons. We have carried out this sequence with success using a number of other alcohol derivatives, including tertbutyldimethylsilyl and methyl ethers as well as acetates.
18. Olofson, R. A.; Martz, J. T.; Senet, J.-P.; Piteau, M.; Malfroot, T. J. Org. Chem. 1984, 49, 2795-2799.
19. Meyers provides an alternative procedure for auxiliary removal for compounds intolerant of hydrogenolytic conditions. This involves transformation of the primary alcohol of the auxiliary to a thiophenyl derivative using triethylphosphine and diphenyl disulfide and then treatment with lithio di-tert-butylbiphenyl (51% overall yield; see ref 2a).
20. The multi-kilogram preparation of U-93385 by this chemistry was carried out by Dr. Michael F. Lipton and his associates Michael A. Mauragis and Michael F. Veley, Chemical Research Preparations, Pharmacia and Upjohn, Inc.
21. For a related reaction, see Vedejs, E.; Wilde, R.G.J. Org. Chem. 1986, 51, 117-119.
22. During the preparation of this manuscript, an example of condensations similar to these appeared: Ragan, J. A.; Claffey, M. C. Heterocycles 1995, 41, 57-70. We thank Dr. Ragan for alerting us to these results.