phenylene diamine 4 was converted to the di-SES derivative
5b and the same coupling/oxidation sequence was applied,
providing diimide substrate 8b. Employment of the annula-
tion conditions as described above cleanly provided di-
hydroquinoline 9b. Treatment of the SES-protected di-
hydroquinoline 9b with TBAF or with potassium carbonate
resulted in aromatization with regiospecific loss of one of
the two SES groups and quantitative formation of quinoline
10. Liberation of the second amino group to afford p-amino
quinoline 11 was achieved by stirring intermediate 10 in 50%
sulfuric acid for 20 h.
Testing the scope of the new annulation methodology with
vinyl quinone monoimide substrates was of particular interest
because it would provide 6-hydroxy quinolines. 6-Oxygen-
ated quinoline systems appear in the structures of a number
of medicinally interesting and synthetically challenging
natural products, including those of quinine, streptonigrin,
and the luzopeptins.14
Resorting again to the use of the SES protecting group,
we prepared monoimide 15b (Scheme 4) and subjected it to
the cyclization conditions. This substrate proved to be stable
at room temperature in the toluene/HMPA medium. How-
ever, when the solution was stirred at reflux in the dark,
reaction was complete in 1 h and SES-protected dihydro-
quinoline 16b was isolated in satisfying yields. Treatment
of this compound with either base or a fluoride source
effected both deprotection and aromatization, affording
6-hydroxyquinoline 17 in quantitative yields.
Remarkably, exposure of the same annulation reaction
mixtures (monoimide 15a or 15b in toluene containing 0.5%
HMPA)16 to light at room temperature resulted in total
conversion of the substrate to the protected indole (18a and
18b) rather than to the protected dihydroquinoline system
(Scheme 6).17 Deprotection of each of these products
The synthesis of vinyl quinone monoimides is outlined in
Scheme 4. The protected aminophenol 12a15 underwent Stille
coupling with stannane 6, and the resulting TES-ether 13a
was deprotected to give phenol 14a. Oxidation afforded the
desired annulation substrate 15a.
Scheme 6. Photochemical Reaction Conditions Yield Indole
Productsa
As anticipated, addition of HMPA to a toluene solution
of monoacetimide substrate 15a at room temperature in the
dark effected clean conversion to dihydroquinoline 16a,
successfully extending the methodology to 6-hydroxy quino-
line systems (Scheme 5). However, attempts to remove the
a (a) For 15a: 5 mM in toluene, 0.5% HMPA, hV, rt (69%). For
15b: 2 mM in toluene, 0.5% HMPA, hV, rt (59%); (b) NaOMe,
MeOH, rt (quantitative); (c) CsF, DMF, rt (quantitative).
Scheme 5. Annulation of Monoimide Substrates and
Conversion of Dihydroquinolines to 6-Hydroxy Quinolinesa
provided the corresponding 5-hydroxy indoleacetic acid ester
1918 in quantitative yield.
Although the photochemical isomerization of vinyl qui-
nones to benzofurans is known,19 the corresponding conver-
sion of vinyl quinone imides to indoles is a new reaction. In
the systems examined so far, the mild conditions required
and the simplicity of the procedure were dazzling.
The synthesis of quinolines and indoles by a short
sequence based on Stille coupling of protected bromo
diamines and amino phenols followed by electrocyclization
a (a) For 15a: 5 mM in toluene, 5% HMPA, rt, dark (71%). For
15b: 2 mM in toluene, 2.5% HMPA, reflux, dark (58%); (b) for
16b: K2CO3, DMF, 50 °C or CsF, DMF, rt (quantitative).
(14) Total syntheses of each of these targets have been reported. For
quinine, see: Stork, G.; Niu, D.; Fujimoto, A.; Koft, E. R.; Balkovec, J.
M.; Tata, J. R.; Dake, G. R. J. Am. Chem. Soc. 2001, 123, 3239-3242. For
streptonigrin, see: Boger, D. L.; Panek, J. S.; Duff, S. R. J. Am. Chem.
Soc. 1985, 107, 5745-54. For luzopeptins, see: Boger, D. L.; Ledeboer,
M. W.; Kume, M.; Searcey, M.; Jin, Q. J. Am. Chm. Soc. 1999, 121, 11375-
11383. Valognes, D.; Belmont, P.; Xi, N.; Ciufolini, M. A. Tetrahedron
Lett. 2001, 42, 1907-1909.
acetyl group from this cyclization product, under conditions
such as those applied to diacetamide 9a, provided neither
dihydroquinoline nor quinoline.13
(9) Tidwell, J. H.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 11797-
11810.
(15) For the preparation of protected amino phenols 12a and 12b, see
Supporting Information.
(10) Collins, P. W.; Kramer, S. W.; Gasiecki, A. F.; Weier, R. M.; Jones,
P. H.; Gullikson, G. W.; Bianchi, R. G. J. Med. Chem. 1987, 30, 193-
197.
(11) SES ) trimethylsilylethanesulfonyl (Weinreb, S. M.; Demko, D.
M.; Lessen, T. A. Tetrahedron Lett. 1986, 27, 2099-2102).
(12) With the diimides, the rate of reaction accelerated with the amount
of HMPA added up to approximately 5 vol %.
(13) Basic reaction conditions (NaOMe, MeOH) left dihydroquinoline
9a unchanged, whereas acidic conditions (AcOH or up to 37% HCl) resulted
in the formation of decomposition products.
(16) Employment of higher concentrations of HMPA resulted in the
formation of mixtures of dihydroquinoline and indole products.
(17) The formation of indole products from diimide substrates 8a and
8b was not observed even after prolonged exposure to light or upon
irradiation in a photochemical reactor in toluene containing HMPA.
(18) Related indoles have been used in nonpeptidic neurotensin mimetics;
see: Dodd, D. S.; Kozikowski, A. P.; Cusack, B.; Richelson, E. Bioorg.
Med. Chem. Lett. 1994, 4, 1241-1246.
(19) Iwamoto, H.; Takuwa, A.; Hamada, K.; Fujiwara, R. J. Chem. Soc.,
Perkin Trans. 1 1999, 575-581.
Org. Lett., Vol. 4, No. 24, 2002
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