Scheme 1a
Scheme 2a
a Reagents and conditions: (a) (i) s-BuLi/TMEDA, THF, -80
°C, 1 h, (ii) ZnCl2, -80 °C, 1 h, (iii) CuCN‚2LiCl, -80 °C, 1 h,
(iv) (3-bromoprop-1-ynyl)trimethylsilane 5, -80 °C to room temp-
erature (85%). (b) DIBAL/BuLi, THF, 25 °C, 18 h (68%). (c) BuLi/
1-TMS-1,7-octadiyne, THF (82%). (d) (i) NH4F/Bu4NHSO4, CH2Cl2,
48 h, (ii) TBDMSOTf, 2,6-lutidine, CH2Cl2, 25 °C, 2 h (95%).
a Reagents and conditions: (a) 5% CpCo(ethene)2, Et2O, -80
°C to room temperature, 18 h, or 5% CpCo(CO)2, toluene, reflux,
hν, 4 h (66%). (b) 8 equiv of [Ag(Py)2]MnO4, CH2Cl2, 25 °C, 18
h (63%). (c) hν, air, CHCl3, 25 °C, 18 h (61%).
anthracene 13 (55% yield and 16% isolated starting material).
In the case of CpCo(CO)2 the reaction had been carried out
in toluene under reflux and irradiation with a tungsten lamp
(66% yield). Oxidation of 13 with the aid of the mild reagent
[Ag(Py)2]MnO4 gave the anthraquinone 14 (63% yield).18
We have also been trying to oxidize with CrO3 in AcOH,
but these conditions led to decomposition of the anthracene.
The introduction of the C-1 carbonyl was achieved by
photooxidation, a general method for the angucyclinones
developed by Krohn.19 Exposure of 14 to visible light
(tungsten lamp) gave the typical structure 15 of the angucy-
clinone antibiotics (61% yield).
In conclusion, the angucyclinone framework 15 was
synthesized from benzamide 6 in 8 steps and 11% yield
overall. This method provides a new access toward the
angucyclinone antibiotics, which do not have a hydroxy
group at C-6. The stereocenter at C-3 is not involved in the
[2+2+2]-cycloaddition, therefore this methodology offers
a good strategy for the enantioselective synthesis of this class
of antibiotics.
can also promote alkyne trimerization,10 were not successful
in our systems. Two-step oxidation of 13 led then to the
angucyclinone core 15.
The amide 611 was at first selectively ortho-lithiated with
s-BuLi/TMEDA.12b It was then transmetalated with ZnCl2
and then CuCN‚2LiCl and allowed to react with (3-
bromoprop-1-ynyl)trimethylsilane 5 to give the propynyl-
amide 7.12c This was directly reduced to benzaldehyde 8 with
the DIBAL/BuLi complex.13 After addition of lithiated
1-TMS-1,7-octadiyne14 to this aldehyde, the triple bonds of
the resulting triyne 9 were deprotected with NH4F15 (depro-
tection with TBAF in THF led to decomposition of the triyne
9). The hydroxy group was then transformed into its silyl
ether 11 with the aid of TBDMSOTf.16
For the cyclization of 11 we used CpCo(ethene)217and the
commercially available CpCo(CO)2. Reaction of 11 with 5%
CpCo(ethene)2 succeeded under mild conditions at low
temperature. Surprisingly we observed the loss of the
TBDMSO-group with concomitant aromatization to the
Acknowledgment. The authors are grateful to the Fonds
der Chemischen Industrie and the EU-Comission, Directorate
XII, for financial support.
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9562.
Supporting Information Available: Experimental pro-
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13C NMR spectra for 13, 14, and 15. This material is
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