S. Zhang, C. Wan, Q. Wang, B. Zhang, L. Gao, Z. Zha, Z. Wang
SHORT COMMUNICATION
rated that 3a was the intermediate in the reaction. More- acetylene bond to afford either flavone (2a, major) or
over, water and the functional triple bond had a great influ- aurone (2aЈ, minor).
ence on the reaction. When a drop of water was added to
the reaction mixture, only a trace amount of the desired
product was observed, whereas the reaction gave the prod-
uct in good yield under anhydrous conditions (Supporting
Information, Scheme S5). In contrast, intermediate 3a can
be converted into product 2a smoothly, regardless of the
presence of water (Supporting Information, Scheme S6).
This indicated that deprotonation of the propargyl carbinol
Conclusions
In summary, a new synthetic route to chromone deriva-
tives was developed. This reaction can be carried out by
virtue of aerobic oxidation without any assistance of a tran-
sition metal. The 6-endo-dig cyclization product was proba-
bly generated through a cascade oxidative cyclization pro-
was crucial for this conversion. When the triple bond in the
cess under mild conditions. The reaction generally showed
substrate was replaced with a single bond, only the oxidized
a broad substrate scope and high regioselectivities. In ad-
dition, LiOtBu played a crucial role in the oxidation of o-
ketone product was obtained in a low yield (Supporting In-
formation, Scheme S3). In comparison with this result, an
hydroxyphenyl propargyl carbinols. Experiments to eluci-
unknown mixture was obtained when the triple bond was
date the mechanism of this reaction are currently underway
in our laboratory.
replaced with a double bond (Supporting Information,
Scheme S4). This perhaps suggests that the lithium ion is
very important in the reaction, and it is possible that the
lithium ion bridged the oxygen anion of the phenol group
because of the similarity of the lithium ion to a proton.
Experimental Section
Perhaps this complex, on the basis of the bridged, bond
blocked the oxidation of the phenol anion to the quinone
derivatives and promoted the cyclization process.
On the basis of the above experiments, a plausible
mechanism is proposed (Scheme 1). First, lithium phenolate
1x is quickly generated from 1a in the presence of LiOtBu,
followed by the oxidation of the benzylic hydroxy group to
give ketone 1y and protonated intermediate 3a in air atmo-
sphere. This oxidation involves the generation of hydride,
which is oxidized to lithium hydroxide under atmospheric
General Procedure: LiOtBu (0.36 mmol, 1.2 equiv.) was added to
appropriate carbinol 1a–n (0.3 mmol) in dry DMF (2 mL) at room
temperature. The mixture was stirred for 5 min and then heated to
60 °C for 2–4 h. The reaction was monitored by TLC until com-
plete conversion of the starting material. The mixture was then
quenched with a saturated solution of NH4Cl, and the aqueous
phase was extracted with EtOAc. The combined organic layer was
washed with brine, dried with Na2SO4, and concentrated. Crude
products 2a–n were purified by chromatography (petroleum ether/
ethyl acetate = 5:1 v/v).
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details for the control experiment are presented
and copies of the 1H NMR and 13C NMR spectra for all products.
conditions.
A similar mechanism was reported pre-
viously.[15,16] At the same time, acting as a Lewis acid, the
lithium ion coordinates to the carbonyl oxygen atom and,
as such, increases the reactivity of triple bond, which thus
promotes the attack of the phenolic hydroxy ion to the
Acknowledgments
We thank the National Natural Science Foundation of China
(NSFC) (grant numbers 21272222, 21172205, 20772118, 20932002,
20972144, 91213303, J1030412) for support.
[1] G. Cainelli, G. Cardillo, Chromium Oxidations in Organic
Chemistry, Springer, Berlin, 1984.
[2] R. A. Sheldon, J. K. Kochi, Metal-Catalysed Oxidations of Or-
ganic Compounds, Academic Press, New York, 1981.
[3] a) T. Naota, H. Takaya, S. I. Murahashi, Chem. Rev. 1998, 98,
2614–2617; b) R. A. Sheldon, I. W. C. E. Arends, A. Dijksman,
Catal. Today 2000, 57, 157–166.
[4] a) B. A. Steinhoff, S. S. Stahl, J. Am. Chem. Soc. 2006, 128,
4348–4355; b) G. J. Brink, I. W. C. E. Arends, M. Hoogenraad,
G. Verspui, R. A. Sheldona, Adv. Synth. Catal. 2003, 345, 497–
505; c) N. Kakiuchi, Y. Maeda, T. Nishimura, S. Uemura, J.
Org. Chem. 2001, 66, 6620–6625; d) T. Nishimura, N. Kakiuchi,
M. Inoue, S. Uemura, Chem. Commun. 2000, 1245–1246; e) T.
Nishimura, T. Onoue, K. Ohe, S. Uemura, J. Org. Chem. 1999,
64, 6750–6755; f) K. P. Peterson, R. C. Larock, J. Org. Chem.
1998, 63, 3185–3189.
[5] a) C.-F. Wan, J.-M. Fan, J.-T. Zhang, Z.-Y. Wang, Chin. Sci.
Bull. 2010, 55, 2817–2819; b) I. E. Markó, A. Gautier, R. Du-
meunier, K. Doda, F. Philippart, S. M. Brown, C. J. Urch, An-
gew. Chem. 2004, 116, 1614; Angew. Chem. Int. Ed. 2004, 43,
1588–1591; c) P. Gamez, I. W. C. E. Arends, J. Reedijka, R. A.
Sheldon, Chem. Commun. 2003, 2414–2415; d) P. Chaudhuri,
Scheme 1. Plausible mechanism of the LiOtBu-mediated oxidative
cyclization of 2-(1-hydroxy-3-phenylprop-2-yn-1-yl)phenol (1a).
2082
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 2080–2083