Combinatorial Synthesis of C(2), C(3)-Disubstituted 3-Hydroxypropionamides Utilizing Baylis-Hillman Reactions on Solid Support

Synlett

Volumn 1997, Issue 3, 1997, Pages 325-326

  Prien, O ^a   Rolfing K ^a   Thiel, M ^a   Kunzer H ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0039188094     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1997-769     Document Type: Article

References (19)

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4. (c) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527.
5. (a) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653.
6. (b) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996, 52, 8001.
7. (a) Ameer, F.; Drewes, S. E.; Freese, S.; Kaye, P. T. Synth. Commun. 1988, 18, 495.
8. (b) Drewes, S. E.; Freese, S. D.; Emslie, N. D.; Roos, G. H. P. Synth. Commun. 1988, 18, 1565.
9. For a recent example, see: Perlmutter, P.; Tabone, M. J. Org. Chem. 1995, 60, 6515.
10. (a) House, H. O.; Crumrine, D. S.; Teranishi, A. Y.; Olmstead, H. D. J. Am. Chem. Soc. 1973, 95, 3310.
11. (b) Heathcock, C. H.; Pirrung, M. C.; Sohn, J. E. J. Org. Chem. 1979, 44, 4294.
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13. (a) Basha, A.; Lipton, M.; Weinreb, S. M. Tetrahedron Lett. 1977, 18, 4171.
14. (b) Ley, S. V.; Mynett, D. M.; Koot, W.-J. Synlett 1995, 1017.
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16. Darling, G. D.; Fréchet, J. M. J. J. Org. Chem. 1986, 51, 2270. 2-Hydroxyethyl polystyrene is commercially available from Rapp Polymere GmbH, Ernst Simon Str. 9, D-72072 Tübingen, Germany.
17. Yedidia, V.; Leznoff, C. C. Can. J. Chem. 1980, 58, 1144.
18. The Syro workstation offered by MultiSynTech GmbH, Am Neggenborn 113, D-44892 Bochum, Germany, was used for this purpose.
19. Physical data for selected compounds are as follows. 3a: mp 99-101°C (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) 5 8.19 (d, J = 8.8 Hz. 2 H). 7.53 (d, J = 8.7 Hz, 2 H), 7.22 (s. l H), 5.1 l(d, J =8.7 Hz, 1 H), 3.44 (s, 3 H), 3.09-2.69 (serm, 11 H); 13C NMR (75 MHz, CDCl,) 5 171.3, 149.0, 147.6, 127.5, 123.5,76.9, 61.0,55.4,51.9,49.2,27.9.3b:mpl05-106°C(pentane/ether);lH NMR (300 MHz, CDCl3) 8 8.18 (d. J = 8.8 Hz, 2 H), 7.40 (d, J = 8.6 Hz, 2 H). 5.82 (d, J = 8.3 H?,. 1 H), 5.28 (dd, J = 8.2 Hz, J = 4.5 Hz, 1 H), 3.63 (s, 3 H), 3.29-2.47 (ser m, 11 H); 13C NMR (75 MHz, CDCl1) 5 172.3, 149.3. 147.4, 126.8, 123.5,73.7,56.8,55.3, 52.0, 47.9, 27.9. 4a: mp 101-102 0C (ether/dichloromethane); 1H NMR (300 MHz. CDCl3) 5 8.19 (d. J = 8.7 Hz. 2 H), 7.55 (d, J = 8.6Hz, 2 H), 6.53 (br s, 1 H), 6.18 (s, 1 H), 5.31 (d. J = 6.0 Hz, IH), 3.17-2.52 (ser m, 13 H), 1.35-1.09 (ser m, 4 H), 0.84 (t, J = 7.2 Hz, 3 H); 13C NMR (75 MHz. CDCI3)O 171.6, 149.4, 147.3, 127.1. 123.5, 74.7, 58.9, 55.2, 49.1, 38.9, 31.4, 28.0, 20.0, 13.6. lOaaiic: 1H NMR (300 MHz, CDCl3) S 7.96 (dd, J = 8.2 Hz. y = 1.3 Hz. 1 H), 7.92 (dd, J =8.0 Hz, J = 1.2Hz, 1 H),7.78(brs, 1 H), 7.67 (td, y = 7.6Hz,y= 1.2Hz, ! H). 7.44 (td,/= 8.4 Hz, J = 1.4Hz, 1 H), 7.18-7.01 (serm, 4 H), 6. Il (d,7 = 6.9Hz, 1 H), 5.47 (m, 1 H).3.80 (1/2 ABq, J= 15.0Hz, 1 H), 3.61 (1/2 ABq, J= 15.0Hz, 1 H), 3.22-2.66 (serm, 9H), 1.60(mc, 1 H), 0.73 (d, J = 6.7 Hz, 6 H). lObaiK: 1H NMR (300 MHz, CDCl3) S 7.86 (dd. 7 = 8.1 Hz, J = 1.2 Hz, 1 H), 7.76 (dd, J = 7.9 Hz, J = 1.2 Hz, I H), 7.59 (td, J = 7.5 Hz, y =1.2 Hz, I H), 7.43 (td,y =8.1 Hz, J =1.3 Hz, I H), 7.17-6.95 (ser m, 5 H). 5.83 (s, 1 H), 5.80 (d, J = 4.8 Hz, 1 H), 3.64 (1/2 ABq, J= 15.0Hz. 1 H). 3.57 (1/2 ABq, J= 15.0 Hz, 1 H), 3.09-2.65 (serm,9 H), 1.61