W. Zhang, Y. Lu, C. H.-T. Chen, D. P. Curran, S. Geib
SHORT COMMUNICATION
Scheme 5. Synthesis of benzodiazepinedione-fused tetracyclic compounds 4a–c. a) 2-nitrobenzoylchloride (3 equiv.), Et3N (2 equiv.),
DMF, 80 °C, 2 h, F-SPE. b) Zn dust (10 equiv.), AcOH, sonication, 25 °C, 2 h, F-SPE, 65–71%. c) DBU (2 equiv.), dioxane, microwave
(130 °C, 5 min), F-SPE, HPLC.
the N-acylation reaction was sensitive to R1 substitution;
ath, Acc. Chem. Res. 1998, 31, 641–650; j) A. Studer, S. Hadida,
S. Y. Ferritto, P. Y. Kim, P. Jeger, P. Wipf, D. P. Curran, Science
only small R1 groups such as H and Me gave products in
1997, 275, 823–826; k) I. T. Horvath, T. Rabai, Science 1994,
good yields. Compounds 9 were then treated with zinc dust
in acetic acid under sonication to reduce the nitro group
and form 10. The cyclative tag cleavage of compounds 10 [4]
with DBU produced tricyclic compounds 4a–c in 45–58%
yields.
266, 72–76.
[3]
C. H.-T. Chen, W. Zhang, Mol. Diversity 2005, 9, 353–359.
a) D. P. Curran, Synlett 2001, 1488–1496; b) D. P. Curran in
Handbook of Fluorous Chemistry (Eds.: J. A. Gladysz, D. P.
Curran, I. T. Horvath), Wiley-VCH, Weinheim, 2004, p. 101.
a) W. Zhang, T. Nagashima, Y. Lu, C. H.-T. Chen, Tetrahedron
Lett. 2004, 45, 4611–4613; b) W. Zhang, C. H.-T. Chen, Y. Lu,
T. Nagashima, Org. Lett. 2004, 6, 1473–1476; c) W. Zhang,
Y. Lu, C. H.-T. Chen, Mol. Diversity 2003, 7, 199–202; d) K.
Olofeeson, S.-Y. Kim, M. Larhed, D. P. Curran, A. Hallberg,
J. Org. Chem. 1999, 64, 4539–4541; e) M. Larhed, M. Hoshino,
S. Hadida, D. P. Curran, A. Hallberg, J. Org. Chem. 1997, 62,
5583–5587.
a) Y. Lu, W. Zhang, Mol. Diversity 2005, 9, 91–98; b) W.
Zhang, C. H.-T. Chen, Tetrahedron Lett. 2005, 46, 1807–1810;
c) Y. Lu, W. Zhang, QSAR Comb. Sci. 2004, 23, 827–835; d)
W. Zhang, P. Tempest, Tetrahedron Lett. 2004, 45, 6757–6760.
W. Zhang, Y. Lu, S. Geib, Org. Lett. 2005, 7, 2269–2272.
Selected papers on fluorous mixture synthesis: a) Q. Zhang,
D. P. Curran, Chem. Eur. J. 2005, 11, 4866–4880; b) W. Zhang,
Arkivoc 2004, 101–109; c) W. Zhang, Z. Luo, C. H.-T. Chen,
D. P. Curran, J. Am. Chem. Soc. 2002, 124, 10443–10450; d) Z.
Luo, Q. Zhang, Y. Oderaotoshi, D. P. Curran, Science 2001,
291, 1766–1769.
[5]
Conclusion
In summary, we have developed the synthetic routes to
three triaza tricyclic and tetracyclic ring systems by using
the common intermediates generated by [3+2] cycloaddition
of azomethine ylides. Microwave-assisted fluorous synthesis
speeds up reactions and simplifies product purification.
These heterocyclic compounds with variations in ring skel-
[6]
[7]
[8]
eton, stereochemistry, and substitution are good candidates
for diversity-oriented syntheses.
Supporting Information (see footnote on the first page of this arti-
cle): General experimental procedures and analytical data for repre-
sentative intermediates and all final products are provided.
[9]
a) K. Goto, T. Miura, D. Hosaka, H. Matsumoto, M. Mizuno,
H.-k. Ishida, T. Inazu, Tetrahedron 2004, 60, 8845; b) V. Mon-
tanari, K. Kumar, J. Am. Chem. Soc. 2004, 126, 9528–9529; c)
M. Mizuno, K. Goto, T. Miura, D. Hosaka, T. Inazu, Chem.
Commun. 2003, 972; d) P. C. de Visser, M. van Helden, D. V.
Filippov, G. A. van der Marel, J. W. Drijfhout, J. H. van Boom,
D. Noortc, H. S. Overkleeft, Tetrahedron Lett. 2003, 44, 9013–
9016; e) D. V. Filippov, D. J. van Zoelen, S. P. Oldfield, G. A.
van der Marel, H. S. Overkleeft, J. W. Drijfhout, J. H.
van Boom, Tetrahedron Lett. 2002, 43, 7809–7812.
Acknowledgments
This work was supported by the National Institute of General
Medical Sciences SBIR Grants (2R44GM062717-02 and
2R44GM067326-02). We thank Professor Peter Wipf and Dr. John
Hodges for helpful suggestions and discussions.
[1] D. P. Curran, Angew. Chem. Int. Ed. 1998, 37, 1175–1196.
[10]
a) L. Manzoni, R. Castelli, Org. Lett. 2004, 6, 4195–4198; b)
Y. Jing, X. Huang, Tetrahedron Lett. 2004, 45, 4615–4618; c)
T. Miura, K. Goto, D. Hosaka, T. Inazu, Angew. Chem. Int.
Ed. 2003, 42, 2047–2051; d) L. Manzoni, Chem. Commun.
2003, 2930–2931; e) E. R. Palmacci, M. C. Hewitt, P. H. Seeb-
erger, Angew. Chem. Int. Ed. 2001, 40, 4433–4437; f) D. P. Cur-
ran, R. Ferritto, Y. Hua, Tetrahedron Lett. 1998, 39, 4937–
4940.
[2] Selected reviews and monographs on fluorous synthesis: a)
J. A. Gladysz, D. P. Curran, I. T. Horvath (Eds.), Handbook of
Fluorous Chemistry, Wiley-VCH, Weinheim, 2004; b) W.
Zhang, Chem. Rev. 2004, 104, 2531–2556; c) W. Zhang, Curr.
Opin. Drug Disc. Dev. 2004, 7, 784–797; d) G. Pozzi, I. Shepper-
son, Coord. Chem. Rev. 2003, 242, 115–124; e) W. Zhang, Tetra-
hedron 2003, 59, 4475–4489; f) A. P. Dobbs, M. R. Kimberley,
J. Fluorine Chem. 2002, 118, 3–17; g) C. C. Tzschucke, C.
Markert, W. Bannwarth, S. Roller, A. Hebel, R. Haag, Angew.
Chem. Int. Ed. 2002, 41, 3964–4000; h) L. P. Barthel-Rosa, J. A.
Gladysz, Coord. Chem. Rev. 1999, 190–192, 587; i) I. T. Horv-
[11]
[12]
T. Nagashima, W. Zhang, J. Comb. Chem. 2004, 6, 942–949.
Recent reviews and monographs on [3+2] cycloadditions of
azomethine ylides: a) I. Coldham, R. Hufton, Chem. Rev. 2005,
2058
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