1062
Y. Wada et al. / Tetrahedron 65 (2009) 1059–1062
3. Conclusion
Research for Exploratory Research from Japan Society for the
Promotion of Science. Y.W. thanks the Japan Society for the Pro-
motion of Science (JSPS) for a Research Fellowship for Young
Scientists.
In summary, we succeeded in the development of an efficient
synthetic method for the 16,17-dehydropyrroloiminoquinone unit,
observed in discorhabdin alkaloids, using a catalytic amount of
NaN3. The first asymmetric total synthesis of prianosin B in 1.3%
References and notes
total yield over 10 steps from the known
hydrochloride was then achieved.
L-tyrosine methyl ester
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4. Experimental section
4.1. General
The 1H NMR spectra were measured by 300 MHz or 270 MHz
spectrometer with tetramethylsilane as the internal standard at 20–
25 ꢀC. IR spectra were recorded by a diffuse reflectance measure-
ment of samples dispersed in KBr powder. E. Merck silica gel 60 for
column chromatography and E. Merck pre-coated TLC plates, silica
gel F254, for preparative thin-layer chromatography were used.
4.2. Dehydrogenation reaction using a catalytic amount of
NaN3 (Table 2, entry 20)
2. D’Ambrosio, M.; Guerriero, A.; Chiasera, G.; Pietra, F. Tetrahedron 1996, 52, 8899–
8906.
NaN3 (0.013 mmol) was added to a solution of spirodienone 3
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mixture was allowed to warm to 70 ꢀC and stirred for 1 h. The re-
action mixture was quenched by H2O and extracted with AcOEt.
Organic phase was washed by H2O (ꢂ3) and brine (ꢂ1). Organic
phase was dried over Na2SO4 and evaporated in vacuo. Residue was
purified by SiO2 column chromatography (CH2Cl2/MeOH¼20:1) to
give compound 5 (26.5 mg, 66%) as red solid.
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428–430; (e) Nishiyama, S.; Cheng, J.-F.; Tao, X.-L.; Yamamura, S. Tetrahedron
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kura, T. J. Am. Chem. Soc. 1992, 114, 2175–2180; (g) Izawa, T.; Nishiyama, S.; Ya-
mamura, S. Tetrahedron 1994, 50, 13593–13600; (h) White, J. D.; Yager, K. M.;
Yakura, T. J. Am. Chem. Soc. 1994, 116, 1831–1838; (i) Sadanandan, E. V.; Pillai, S.
K.; Lakshmikantham, M. V.; Billimoria, A. D.; Culpepper, J. S.; Cava, M. P. J. Org.
Chem. 1995, 60, 1800–1805; (j) Ciufolni, M. A.; Dong, Q.; Yates, M. H.; Schunk, S.
Tetrahedron Lett. 1996, 37, 2881–2884; (k) Peat, A. J.; Buchwald, S. L. J. Am. Chem.
Soc. 1996, 118, 1028–1030; (l) Roberts, D.; Joule, J. A.; Bros, M. A.; Alvarez, M. J.
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2103–2110; (n) Makosza, M.; Stalewski, J.; Maslennikova, O. S. Synthesis 1997,
1131–1133; (o) Kita, Y.; Watanabe, H.; Egi, M.; Saiki, T.; Fukuoka, Y.; Tohma, H. J.
Chem. Soc., Perkin Trans. 1 1998, 635–636; (p) Kraus, G. A.; Selvakumar, N. J. Org.
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Tetrahedron 1998, 54, 8999–9010; (r) Aubart, K. M.; Heathcock, C. H. J. Org. Chem.
1999, 64, 16–22 and references therein; For total syntheses of discorhabdin A,
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Angew. Chem., Int. Ed. 2002, 41, 348–350; (t) Tohma, H.; Harayama, Y.; Ha-
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Compound 5: red solid; mp >300 ꢀC; 1H NMR (300 MHz,
CDCl3):
d
¼8.00 (d, 1H, J¼6.0 Hz), 7.89 (s, 1H), 7.28 (d, 1H, J¼6.0 Hz),
7.24 (d, 2H, J¼9.6 Hz), 6.23 (d, 2H, J¼9.6 Hz), 3.54 (m, 2H), 1.90 ppm
(dd, 2H, J¼6.0, 3.9 Hz); 13C NMR (125.65 MHz, DMSO-d6):
¼185.4,
d
165.3, 156.8 (2C), 145.6, 141.2, 126.1 (2C), 111.2, 106.1, 106.0 (2C),
105.9, 105.8 (2C), 40.9, 37.2, 34.6 ppm; IR (KBr): 3313, 3115, 1651,
1601, 1539, 1487 cmꢁ1; HRMS (FAB): calcd for C18H14N3O2 [MþH]þ:
304.1086, found: 304.1085.
4.3. Total synthesis of prianosin B
NaN3 (1.1 mg, 0.0175 mmol) was added to a solution of com-
pound 7 (99.7 mg, 0.175 mmol) in DMF (0.3 mL) at rt under N2 at-
mosphere. The mixture was allowed to warm to 70 ꢀC and stirred for
1 h. The reaction mixture was quenched by H2O and extracted with
AcOEt. Organic phase was washed by H2O (ꢂ3) and brine (ꢂ1). Or-
ganic phase was dried over Na2SO4 and evaporated in vacuo. Residue
was purified by SiO2 column chromatography (CH2Cl2/MeOH¼20:1)
5. Izawa, T.; Nishiyama, S.; Yamamura, S. Tetrahedron 1994, 48, 13593–13600.
6. The condensation of tyramine with iminoquinone was carried out according to
Ref. 4r. Spiro-cyclization was carried out by using PIFA according to Ref. 4t.
7. Alvarez, M.; Bros, M. A.; Gras, G.; Ajana, W.; Joule, J. A. Eur. J. Org. Chem. 1999,
1173–1183.
23
to give prianosin B (35.1 mg, 48%) as red solid. Mp 253 ꢀC; [
a
]
D
þ362
(c 0.405, CHCl3); 1H NMR (500 MHz, CDCl3):
d
¼8.49 (d,1H, J¼5.5 Hz),
8.03 (s,1H), 7.78 (s,1H), 7.54 (d,1H, J¼5.5 Hz), 6.30 (br s,1H), 5.49 (m,
1H), 4.80 (dd,1H, J¼12.0, 6.5 Hz), 2.98 (dd,1H, J¼16.5, 4.0 Hz), 2.87–
8. After finishing to prepare our manuscript, the reaction of N-tosyl-7-methoxy-
iminoquinone (compound A in Scheme 2) with 1.2 equiv of NaN3 in DMF at rt
was reported to cause detosylation. However, no aromatized product was ob-
tained under their reaction conditions (Patel, S. P.; Nadkarni, D. H.; Murugesan,
S.; King, J. R.; Velu, S. E. Synlett 2008, 2864--2868). The fact that only detosy-
lation occurred from A under their conditions also fortifies our deduction about
the reaction mechanism, pathway 3 in Scheme 3. From the results of White’s,
Velu’s, and ours, we conclude that the reaction of pyrroloiminoquinone and
NaN3 in DMF depend on the reaction temperature and the quantity of NaN3. In
the reaction at rt, the use of a large amount of NaN3 causes detosylation and
dehydrogenation (Whites’s result). On the other hand, the use of a equivalent
amount of NaN3 at rt causes only detosylation (Velu’s result). In the reaction at
70 ꢀC, the use of a catalytic amount of NaN3 causes detosylation and de-
hydrogenation (our result).
2.94 ppm (m, 3H); 13C NMR (75.45 MHz, CDCl3):
d
¼188.3, 167.6,
155.7, 146.1, 143.6, 143.0, 129.0 (2C), 125.3, 120.2, 119.6, 118.2, 113.7,
61.7, 56.5, 50.8, 45.6, 40.0 ppm; IR (KBr): 3057, 2924, 2853, 1682,
1645, 1595, 1472, 1303 cmꢁ1; HRMS (FAB): calcd for C18H13BrN3O2S
[MþH]þ: 413.9912, found: 413.9920.
Acknowledgements
This work was financially supported by Grant-in-Aid for
Scientific Research (A) and (B) and Grant-in-Aid for Scientific