K. L. Milkiewicz et al. / Tetrahedron Letters 44 (2003) 7341–7343
7343
1
a reductive amination and acylation in a similar man-
15: H NMR (400 MHz, CDCl3 l): 7.33–7.23 (m, 6H),
7.21–7.13 (m, 3H), 6.77 (s, 1H), 5.27 (d, J=4.9 Hz,
1H), 4.49–4.40 (m, 1H), 3.25 (d, J=11.2 Hz, 1H), 3.20
(d, J=11.2 Hz, 1H), 2.72 (d, J=11.2 Hz, 1H), 2.70–
2.65 (dd, J=4.9 Hz, 11.2 Hz, 1H), 2.41 (s, 3H), 2.26 (d,
J=13.9 Hz, 1H), 1.84–1.74 (m, 1H), 1.58–1.24 (m, 8H).
MS (ESI) m/z 400.10 (MH+).
ner to compound 11.
In conclusion, we have synthesized a diverse series of
10-oxa-3-aza-tricyclo[5.2.1.01,5]dec-8-en-4-ones.
The
selected compounds shown incorporate both hetero-
cyclic and phenyl rings, and alkyl and aryl amides. The
intramolecular Diels–Alder reaction provides a facile
method for the creation of complicated molecules with
3–4 chiral centers and predictable regio- and stereo-
chemistry. Through altering the order of synthetic
steps, one can easily diversify at multiple positions on
the scaffold. The ease of synthesis and the incorpora-
tion of four diversity sites lend themselves to the forma-
tion of large chemical libraries.
1
16: H NMR (400 MHz, CDCl3 l): 7.47–7.41 (m, 1H),
7.37–7.23 (m, 6H), 7.20–7.14 (m, 2H), 6.83 (s, 1H), 5.24
(d, J=4.9 Hz, 1H), 3.25 (d, J=11.2 Hz, 1H), 3.20 (d,
13.9 Hz, 1H), 2.72 (d, J=11.2 Hz, 1H), 2.68 (dd, J=4.8
Hz, 11.2 Hz, 1H), 2.24 (d, J=13.9 Hz, 1H), 1.84–1.73
(m, 1H), 1.57–1.24 (m, 8H), 0.80–0.91 (m, 1H). MS
(ESI) m/z 420.10 (MH+).
Data for selected compounds:
Acknowledgements
1
4: H NMR (400 MHz, CDCl3 l): 7.71–7.65 (m, 2H),
7.42–7.36 (m, 6H), 7.20–7.15 (m, 2H), 6.64 (s, 1H), 5.36
(d, J=4.8 Hz, 1H), 4.39 (d, J=11.2 Hz, 1H), 4.16 (d,
J=11.6 Hz, 1H), 2.72 (dd, J=4.8 Hz, 4.8 Hz, 1H), 1.35
(d, J=11.6 Hz, 1H), 1.17 (s, 3H). MS (ESI) m/z 318.00
(MH+).
The authors thank Mike Kolpak and Karen DiLoreto
for their assistance in running NMR and MS experi-
ments.
1
References
5: H NMR (400 MHz, CDCl3 l): 7.51–7.50 (m, 1H),
7.44–7.43 (m, 1H), 6.49–6.48 (m, 1H), 6.32 (s, 1H), 5.04
(d, J=4.4 Hz, 1H), 4.59–4.50 (m, 1H), 3.81–3.78 (d,
J=11.6 Hz, 1H), 3.66–3.63 (m, J=12.0 Hz, 1H), 2.51
(dd, J=4.8 Hz, 4.8 Hz, 1H), 1.97–1.80 (m, 3H), 1.77–
1.60 (m, 4H), 1.57–1.45 (m, 2H), 1.05 (s, 3H). MS (ESI)
m/z 300.1 (MH+).
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1
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