Complementary selectivity in the alkylation of chiral bicyclic lactam enolates

Journal of Organic Chemistry

Volumn 61, Issue 17, 1996, Pages 5710-5711

  Roth, Gregory P ^a   Leonard, Scott F ^a   Tong, Liang ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BICYCLO[3.3.0]OCTANE DERIVATIVE; LACTAM DERIVATIVE;

ALKYLATION; ARTICLE; CHIRALITY; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; X RAY ANALYSIS;

EID: 0029841581     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo960852a     Document Type: Article

References (14)

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2. Meyers, A. I.; Harre, M.; Garland, R. J. Am. Chem. Soc. 1984, 106, 1146-1148. For the most recent comprehensive review see: Romo, D.; Meyers, A. I. Tetrahedron 1991, 47, 9503-9569.
3. Meyers, A. I.; Wanner, K. Th. Tetrahedron Lett. 1985, 26, 2047-2050.
4. Meyers, A. I.; Lefker, B. A.; Wanner, K. Th.; Aitken, R. A. J. Org. Chem. 1986, 51, 1936-1938.
5. Durkin, K. A.; Liotta, D. J. Am. Chem. Soc. 1990, 112, 8162-8163. Meyers, A. I.; Wallace, R. H. J. Org. Chem. 1989, 54, 2509-2510.
6. Durkin, K. A.; Liotta, D. J. Am. Chem. Soc. 1990, 112, 8162-8163. Meyers, A. I.; Wallace, R. H. J. Org. Chem. 1989, 54, 2509-2510.
7. Carlson, R. G.; Pierce, J. K. J. Org. Chem. 1971, 36, 2319-2324.
8. Masui, M.; Shioiri, T. Tetrahedron 1995, 51, 8363-8370.
9. 1, with a = 7.479(1) Å, b = 14.214(2) Å, c = 16.137(2) Å. There are four molecules in the unit cell. The final R factor is 4.2%, and the final goodness-of-fit value is 0.78. The author has deposited atomic coordinates for 4a and 5d with the Cambridge Crystallographic Data Centre. The coordinates can be obtained, on request, from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
10. 3 at 500 or 600 MHz (approximately 3-5 mg/mL)).
11. Jeener, J.; Meier, B. H.; Bachmann, P.; Ernst R. R. J. Chem. Phys. 1979, 71, 4546-4553.
12. Lefker, B. A. Ph.D. Dissertation, Colorado State University, Fort Collins CO, 1988.
13. 1, with a = 7.764(1) Å, b = 10.568-(3) Å, c = 23.395(7) Å. There are four molecules in the unit cell. The final R factor is 6.8% and the final goodness-of-fit value is 2.02.
14. A single related example has been reported in the literature to give specific exo alkylation but was shown to readily epimerize to a 1:1 exo/endo mixture under thermodynamic conditions. Thottathil, J. K.; Moniot, J. L.; Mueller, R. H.; Wong, M. K. Y.; Kissik, T. P. J Org. Chem. 1986, 51, 3140-3147. With our lactam system this is not the case. Treatment of the methylated lactam 5b at ambient temperature with sodium methoxide in methanol for 18 h only epimerized the newly formed chiral center to a small extent, furnishing 5b with a 10:1 exo/ endo ratio. This is essentially identical to entry 3 in Table 1. equation presented