An efficient chiral moderator prepared from inexpensive (+)-3-Carene: Synthesis of the HIV-1 non-nucleoside reverse transcriptase inhibitor DPC 963

Organic Letters

Volumn 2, Issue 20, 2000, Pages 3119-3121

  Kauffman, Goss S ^a   Harris, Gregory D ^a   Dorow, Roberta L ^a,b   Stone, Benjamin R P ^a   Parsons Jr , Rodney L ^a   Pesti, Jaan A ^a   Magnus, Nicholas A ^a   Fortunak, Joseph M ^a   Confalone, Pat N ^a   Nugent, William A ^a  

^a DUPONT COMPANY   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 CYCLOPROPYLETHYNYL 5,6 DIFLUORO 3,4 DIHYDRO 4 TRIFLUOROMETHYL 2(1H) QUINAZOLINONE; QUINOLONE DERIVATIVE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ARTICLE; ENZYMOLOGY; HUMAN IMMUNODEFICIENCY VIRUS 1; STEREOISOMERISM; SYNTHESIS;

HIV-1; QUINOLONES; REVERSE TRANSCRIPTASE INHIBITORS; STEREOISOMERISM;

EID: 0034609689     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol006321x     Document Type: Article

References (25)

1. (a) Young, S. D.; Britcher, S. F.; Tran, L. O.; Payne, L. S.; Lumma, W. C.; Lyle, T. A.; Huff, J. R.; Anderson, P. S.; Olsen, D. B.; Carroll, S. S.; Pettibone, D. J.; O'Brien, J. A.; Ball, R. G.; Balani, S. K.; Lin, J. H.; Chen, I.-W.; Schleif, W. A.; Sardana, V. V.; Long, W. J.; Brynes, V. W.; Emini, E. A. Antimicrobr. Agents Chemother. 1995, 39, 2602-2605.
2. (b) Pierce, M. E.; Parsons, R. L., Jr.; Radesca, L. A.; Young, S. L.; Silverman, S.; Moore, J. R.; Islam, Q.; Choudhury, A.; Fortunak, J. M. D.; Nguyen, D.; Luo, C.; Morgan, S. J.; Davis, W. P.; Confalone, P. N. J. Org. Chem. 1998, 63, 8536-8543.
3. (c) Patel, M.; Ko, S. S.; McHugh, R. J.; Markwalder, J. A.; Srivastava, A. S.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S. K.; Trainor, G. L.; Seitz, S. P. Biooorg. Med. Chem. Lett. 1999, 9, 2805-2810.
4. (d)) Patel, M.; McHugh, R. J.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S. K.; Trainor, G. L.; Ko, S. S. Biooorg. Med. Chem. Lett. 1999, 9, 3221-3224.
5. (e) Thompson, A. S.; Corley, E. G.; Huntington, M. F.; Grabowski, E. J. J. Tetrahedron Lett. 1995, 36, 8937-8940.
6. (f) Tan, L.; Cheng-Yi, C.; Tillyer, R. D.; Grabowski, E. J. J.; Reider, P. J. Angew. Chem., Int. Ed. 1999, 38, 711-713.
7. Corbett, J. W.; Ko, S. S.; Rodgers, J. D.; Jeffrey, S.; Bacheler, L. T.; Klabe, R. M.; Diamond, S.; Lai, C.-M.; Rabel, S. R.; Saye, J. A.; Adams, S. P.; Trainor, G. L.; Anderson, P. S.; Erickson-Viitanen, S. K. Antimicrobr. Agents Chemother. 1999, 43, 2893-2897.
8. Magnus, N. A.; Confalone, P. N.; Storace, L. Tetrahedron Lett. 2000, 41, 3015-3019.
9. Huffman, M. A.; Yasuda, N.; DeCamp, A. E.; Grabowski, E. J. J. J. Org. Chem. 1995, 60, 1590-1594. For a review of catalytic asymmetric additions to imines, see: Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069-1094.
10. Huffman, M. A.; Yasuda, N.; DeCamp, A. E.; Grabowski, E. J. J. J. Org. Chem. 1995, 60, 1590-1594. For a review of catalytic asymmetric additions to imines, see: Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069-1094.
11. Nugent W. A.; Licini, G.; Bonchio, M.; Bortolmi, O.; Finn, M. G.; McCleland, B. W. Pure Appl. Chem. 1998, 70, 1041-1046.
12. 4 and analyzed by chiral HPLC.
13. Newhall, W. F. J. Org. Chem. 1964, 29, 185. Amino alcohols 6 used in our initial screen were kindly provided by Prof. Bakthan Singaram and Mr Will Chrisman of the University of California, Santa Cruz.
14. In contrast, reaction of (1S,3S,4R)-3,4-epoxycarane with morpholine in the absence of a Lewis acid promoter (100 h, 140°C) is reported to afford 7 in only 11% yield. Fedyunina, I. V.; Plemenkov, V. V.; Bikbulatova, G. Sh.; Nikitina, L. E.; Litvinov, I. A.; Kataeva, O. N. Chem. Nat. Compd. (Engl. Transl.) 1992, 28, 173-177.
15. Currently bulk (+)-3-carene (400 lb drums) costs $4.90 per lb.
16. (a) Brown, H. C.; Suzuki, A. J. Am. Chem. Soc. 1967, 89, 1933-1040.
17. (b) Sonawane, H. R.; Nanjundiah, B. S.; Shah, V. G.; Kulkarni, D. G.; Ahuja, J. R.; Tetrahedron Lett. 1991, 32, 1107-1108.
18. (c) Gianini, M.; von Zelewsky, A. Synthesis 1996, 702-706.
19. 2 to promote rearrangement of epoxides is well-known: House, H. O. J. Am. Chem. Soc. 1955, 77, 5083-5089. Rosenberger, M.; Jackson, W.; Saucy, G. Helv. Chim. Acta 1980, 63, 1665-1674. Serramedan, D.; Marc, F.; Pereyre, M.; Filliatre, C.; Chabardes, P.; Delmond, B. Tetrahedron Lett. 1992, 33, 4457-4460.
20. 2 to promote rearrangement of epoxides is well-known: House, H. O. J. Am. Chem. Soc. 1955, 77, 5083-5089. Rosenberger, M.; Jackson, W.; Saucy, G. Helv. Chim. Acta 1980, 63, 1665-1674. Serramedan, D.; Marc, F.; Pereyre, M.; Filliatre, C.; Chabardes, P.; Delmond, B. Tetrahedron Lett. 1992, 33, 4457-4460.
21. 2 to promote rearrangement of epoxides is well-known: House, H. O. J. Am. Chem. Soc. 1955, 77, 5083-5089. Rosenberger, M.; Jackson, W.; Saucy, G. Helv. Chim. Acta 1980, 63, 1665-1674. Serramedan, D.; Marc, F.; Pereyre, M.; Filliatre, C.; Chabardes, P.; Delmond, B. Tetrahedron Lett. 1992, 33, 4457-4460.
22. 3): δ 15.69, 17.23, 17.31, 18.66, 24.62, 26.71, 28.82, 35.09, 52.66 (br), 67.94, 72.61, 73.31.
23. Details of the X-ray structure are given as Supporting Information. A noteworthy feature is that four independent molecules of 7 are present in the unit cell. In three of these, the cyclohexane conformation is a twist-boat and the O-C-C-N dihedral angle is in the range 91-96°. In the fourth molecule the conformation is a twist-chair with the OH and morpholine nitrogen in pseudoequatorial positions and the dihedral is 60.2°. Thus, although 7 is clearly more rigid than 6, the backbone of 7 still possesses significant flexibility.
24. Thompson, A.; Corley, E. G.; Huntington, M. F.; Grabowski, E. J. J.; Remenar, J. F.; Collum, D. B. J. Am. Chem. Soc. 1998, 120, 2028-2038.
25. 4Cl, and water (25 mL each). Volatiles were removed at reduced pressure, and the residue was dissolved in hot heptane (30 mL). On cooling to 0°C, crystalline (S)-3 was collected by filtration and dried in vacuo (1.62 g, 85% yield, 99.6% ee). Spectroscopic properties were identical to those reported previously (ref 2).