Complementary α-alkylation approaches for a sterically hindered spiro[pyrazolopyranpiperidine]ketone

Tetrahedron Letters

Volumn 53, Issue 20, 2012, Pages 2543-2547

  Limberakis, Chris ^a   Li, Jianke ^a   Balan, Gayatri ^a   Griffith, David A ^a   Kung, Daniel W ^a   Rose, Colin ^a   Vrieze, Derek ^a  

^a PFIZER INC   (United States)

Author keywords

1,4 Addition; Aldol condensation; DMPU; Enolate alkylation; Spiro pyrazolopyranpiperidine ketone

Indexed keywords

ALDEHYDE; ELECTROPHILE; KETONE DERIVATIVE; METHYL IODIDE; SPIRO(PYRAZOLOPYRANPIPERIDINE)KETONE; UNCLASSIFIED DRUG;

ALDOL REACTION; ALKYLATION; ARTICLE; CYCLOPROPANATION; NUCLEOPHILICITY; PROTON NUCLEAR MAGNETIC RESONANCE; ROOM TEMPERATURE;

EID: 84859776954     PISSN: 00404039     EISSN: 18733581     Source Type: Journal    
DOI: 10.1016/j.tetlet.2012.03.030     Document Type: Article

References (44)

1. World Health Organization (WHO) website: http://www.who.int/mediacentre/ factsheets/fs312/en/index.html accessed January 27, 2012.
2. M.P. Bourbeau, J.G. Allen, and W. Gu Annu. Rep. Med. Chem. 45 2010 95 108
3. J.W. Corbett Expert Opin. Ther. Pat. 19 2009 943 956
4. J.W. Corbett, and J.H. Harwood Jr. Recent Pat. Cardiovasc. Drug Disc. 2 2007 162 180
5. K.D. Freeman-Cook, P. Amor, S. Bader, L.M. Buzon, S.B. Coffey, J.W. Corbett, K.J. Dirico, S.D. Doran, R.L. Elliott, W. Esler, A. Guzman-Perez, K.E. Henegar, J.A. Houser, C.S. Jones, C. Limberakis, K. Loomis, K. McPherson, S. Murdande, K.L. Nelson, D. Phillion, B.S. Pierce, W. Song, E. Sugarman, S. Tapley, M. Tu, and Z. Zhao J. Med. Chem. 55 2012 935 942
6. J.W. Corbett, K.D. Freeman-Cook, R. Elliott, F. Vajdos, F. Rajamohan, D. Kohls, E. Marr, H. Zhang, L. Tong, M. Tu, S. Murdande, S.D. Doran, J.A. Houser, W. Song, C.J. Jones, S.B. Coffey, L. Buzon, M.L. Minich, K.J. Dirico, S. Tapley, R.K. McPherson, E. Sugarman, H.J. Harwood, and W. Esler Bioorg. Med. Chem. Lett. 20 2010 2383 2388
7. Corbett, J. W.; Elliott, R. L.; Freeman-Cook, K. D.; Griffith, D. A.; Phillion, Dennis P. PCT Int. Appl. (2009), WO 2009144554 A1.
8. Limberakis, C.; Bader, S.; Buzon, L. M.; Coffey, S. B.; Conway, B. G.; Corbett, J. W.; Freeman-Cook, K. D.; Henegar, K. E.; Jones, C. S.; Nelson, K. L.; Song, W.; Weaver, J. D.; Zhao, Z.; Phillion, D. P. Synthesis of pyrazolospiroketone ACC inhibitors. Abstracts of Papers, 240th ACS National Meeting, Boston, MA, United States, August 22-26, 2010 (2010), MEDI-190.
9. A.R. Angeles, L. Yang, C. Dai, A. Brunskill, A.D. Basso, and M.D. Siddiqui Tetrahedron Lett. 51 2010 6236 6239
10. Z.-M. Border, C. Marais, B.C.B. Bezuidenhoudt, and J.A. Steenkamp Aust. J. Chem. 61 2008 122 130
11. T. Mahapatra, N. Jana, and S. Nanda Tetrahedron: Asymmetry 19 2008 1224 1232
12. A. Yamashita, E.B. Norton, C. Hanna, J. Shim, E.J. Salaski, D. Zhou, and T.S. Mansour Synth. Commun. 36 2006 465 472
13. V.H. Gessner, C. Däschlein, and C. Strohmann Chem. Eur. J. 15 2009 3320 3334
14. X. Sun, and D.B. Collum J. Am. Chem. Soc. 122 2000 2452 2458 Ibid, 2459-2463
15. H.J. Reich, D.P. Green, M.A. Medina, W.S. Goldenberg, N.Ö. Gudmundsson, R.R. Dykstra, and N.H. Phillips J. Am. Chem. Soc. 120 1998 7201 7210
16. P.F. Godenschwager, and D.B. Collum J. Am. Chem. Soc. 129 2007 12023 12031
17. P. Zhao, and D.B. Collum J. Am. Chem. Soc. 125 2003 14411 14424
18. L.M. Pratt, and A. Streitweiser J. Org. Chem. 68 2003 2830 2838
19. Y.-J. Kim, and A. Streitweiser Org. Lett. 4 2002 573 575
20. R.R. Dykstra Encyclopedia of Reagents for Org. Synth. 2001 http://dx.doi.org/10.1002%2F047084289X.rh020
21. A.K. Beck, and D. Seebach Encyclopedia of Reagents for Org. Synth. 2001 http://dx.doi.org/10.1002%2F047084289X.rd366
22. D. Seebach, J.D. Aebi, M. Gander-Coquoz, and R. Naef Helv. Chim. Acta 70 1987 1194 1216
23. T. Mukhopadhyay, and D. Seebach Helv. Chim. Acta 65 1982 385 391
24. Z.J. Song, D.M. Tellers, M. Journet, J.T. Kuethe, D. Lieberman, G. Humphrey, F. Zhang, Z. Peng, M.S. Waters, D. Zewge, A. Nolting, D. Zhao, R.A. Reamer, P.G. Dormer, K.M. Belyk, I.W. Davies, P.N. Devine, and D.M. Tschaen J. Org. Chem. 76 2011 7804 7815
25. J. Clayden, W. Farnaby, D.M. Grainger, U. Hennecke, M. Mancinelli, D.J. Tetlow, I.H. Hillier, and M.A. Vincent J. Am. Chem. Soc. 131 2009 3410 3411
26. J. Clayden, S. Parris, N. Cabedo, and A.H. Payne Angew. Chem., Int. Ed. 47 2008 5060 5062
27. S.E. Denmark, and J.J. Ares J. Org. Chem. 73 2008 9647 9656
28. D.M. Shendage, R. Fröhlich, K. Bergander, and G. Haufe Eur. J. Org. Chem. 2005 719 727
29. J. Yang, R. Mueller, E. Pop, J.-L.H. Dasseux, and D.C. Oniciu Org. Prep. Proced. Int. 36 2004 587 596
30. W.R.F. Goundry, J.E. Baldwin, and V. Lee Tetrahedron 59 2003 1719 1729
31. A.B. Smith, G.K. Friestad, J. Barbosa, E. Bertounesque, K.G. Hull, M. Iwashima, Y. Qiu, B.A. Salvatore, P.G. Spoors, and J.J.-W. Duan J. Am. Chem. Soc. 121 1999 10468 10477
32. 4 (M+1) requires 378.2387].
33. 1 M LiHMDS in tetrahydrofuran or toluene was purchased from Sigma-Aldrich.
34. 3 for several hours. For a related β-elimination see Bagley, S. W.; Southers, J. A.; Cabral, S.; Rose, C. R.; Bernhardson, D. J.; Edmonds, D. J.; Polivkova, J.; Yang, X.; Kung, D. W.; Griffith, D. A.; Bader, S. J. J. Org. Chem. 2012, 77, 1497-1506.
35. L.C. Vishwakarma, O.D. Stringer, and F.A. Davis Org. Synth. 66 1988 203 210
36. F.A. Davis, S. Chattopadhyay, J.C. Towson, S. Lal, and T. Reddy J. Org. Chem. 53 1988 2087 2089
37. L.C. Dias, E.C. de Lucca, M.A.B. Ferreira, D.C. Garcia, and C.F. Tormena Org. Lett. 12 2010 5056 5059
38. J.R. Dunetz, L.D. Julian, J.S. Newcom, and W.R. Roush J. Am. Chem. Soc. 130 2008 16407 16416
39. A.N. Thadani, and V.H. Rawal Encyclopedia of Reagents for Org. Synth. 2004 http://dx.doi.org/10.1002/047084289X.rn00416
40. The α,β-unsaturated ketone 19 was also obtained using the Eschenmoser methylenation: ketone 2 (1 equiv), N,N,N,N′- tetramethylmethylenediamine (4 equiv), AcOH (8 equiv), THF, reflux, 55%.
41. S.F. Martin, J.A. Dodge, L.E. Burgess, C. Limberakis, and M. Hartmann Tetrahedron 52 1996 3229 3246
42. T. Hayashi, and K. Yamasaki Chem. Rev. 103 2003 2829 2844
43. K. Fagnou, and M. Lautens Chem. Rev. 103 2003 169 196
44. N. Saito, M. Masuda, H. Saito, K. Takenouchi, S. Ishizuka, J.-I. Namekawa, M. Takimoto-Kamimura, and A. Kittaka Synthesis 2005 2533 2543