A diastereoselective tandem metalloenamine alkylation/aza-annulation of β-tetralones expedites the synthesis of benzoquinolinones

Tetrahedron Letters

Volumn 37, Issue 24, 1996, Pages 4121-4124

  Audia, James E ^a   Droste, James J ^a   Dunigan, James M ^a   Bowers, John ^a   Heath, Perry C ^a   Holme, Dale W ^a   Eifert, Jill H ^a   Kay, Harry A ^a   Miller, Richard D ^a   Olivares, Jorge M ^a   Rainey, Thomas F ^a   Weigel, Leland O ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZOQUINOLONE DERIVATIVE; BENZOQUINONE DERIVATIVE; ENAMINE; PHENETHYLAMINE; STEROID 5ALPHA REDUCTASE; TETRALIN DERIVATIVE; UNCLASSIFIED DRUG;

ALKYLATION; ARTICLE; DRUG PURIFICATION; DRUG SYNTHESIS; STEREOCHEMISTRY;

EID: 18844467793     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00724-1     Document Type: Article

References (15)

1. Jones, C. D.; Audia, J. E.; Hirsch, K. S.; Lawhorn, D. E.; McQuaid, L. A., Neubauer, B. L.; Pike, A. J.; Pennington, P. A.; Stamm, N. B.; Toomey, R. E. J. Med. Chem. 1993, 36, 421.
2. Rasmusson, G. H.; Reynolds, G. F.; Steinberg, N. G.; Walton, E.; Patel, G. F.; Liang, T.; Casccieri, M. A.; Cheeung, A. H.; Brooks, J. R.; Berman, C. J. Med. Chem. 1986, 29, 2298.
3. For the first diastereoselective aza-annulation of a β-tetralone enamine with acryloyl chloride and the preparation of 3, see: Audia, J. E.; Lawhorn, D. E.; Deeter, J. B. Tetrahedron Lett. 1993, 44, 7001.
4. For an example of methylation of β-tetralones, see: Nixon, J. A.; Pioch, R. P.; Schaus, J. M.; Titus, R. D., European Pat. Appl. ; EP 343830 A2, November 29, 1989.
5. Cannon, J. G.; Chang, Y.; Amoo, V. E.; Walker, K. A. Synthesis 1986, 494.
6. For the first disclosure of this work, see: Weigel, L. O.; Audia, J.; Droste, J.; Dunigan, J.; Heath, P.; Holme, D.; Eifert, J.; Kay, H.; Miller, R.; Olivares, J.; Rainey, T. Abstracts of the 208th National ACS Meeting, ORGN310, August 24, 1994, Washington D.C.
7. For the alkylation of β-tetralone enamines, see: Evans, D. A. J. Am. Chem. Soc. 1970, 92, 7593.
8. For alkylation of PEA imines of cyclohexanone, see: Fraser, R. R.; Akiyama, F.; Banville, J. Tetrahedron Lett. 1979, 20, 3929.
9. For the diastereoselective alkylations of 1-alkyl-2-tetralone enamines derived from PEA with methyl acrylate, see: d'Angelo, J; Volpe, T.; Revial, G.; Pfau, M. Tetrahedron Lett. 1987, 28, 2367.
10. For improved aza-annulations using carboxylic anhydrides, see: Paulvannan, K.; Stille, J. R. J. Org. Chem. 1992, 57, 5319.
11. For pKas of β-tetralones, see: Eldin, S.; Whalen, D. L.; Pollack, R. M. J. Org. Chem. 1993, 58, 3490.
12. For processes applicable to the preparation of 6-bromo-2-tetralone, see: Rosowsky, A.; Battiglia, J; Chen, K. K. N.; Modest, E. J. J. Org. Chem. 1968, 33, 4288.
13. 13C NMR, MS, IR and combustion analyses. (c) The stereochemistry of 14 and several related BQs prepared by similar methods were proven by single crystal X-ray determination (L. O. Weigel, et al., submitted to The 212th National ACS Meeting, August 25, 1996, Orlando, FL). The stereochemical assignments of entries 2-7 (Table 1) were based upon these findings and the diastereoselectivity described in references 3 and 9. (d) The use of (S)-PEA in Scheme 1 afforded a reference sample of ent-14. The ee values of entries 2-7 in Table 1 were based upon the relative retentions by chiral HPLC.
14. For characterization of BQs similar to 13, see: Weigel, L. O. et al., in press J. Org. Chem., 1996.
15. (a) The olefin of 12 was reduced approx 10x faster than cleavage of the auxiliary. (b) Reduction of 12 at 72°C afforded 7% of 15.