Organic Letters
Letter
(3) (a) Wang, H.-L.; Wei, J.-W. Chin. J. Physiol. 2012, 55, 101−107.
(b) Wang, H.-L.; Wang, L.-C.; Wei, J.-W. Chin. J. Physiol. 2013, 56,
11−17.
(4) (a) Landmesser, T.; Linden, A.; Hansen, H.-J. Helv. Chim. Acta
2008, 91, 265−284. (b) Li, Y.; Fan, W.; Xu, H.-W.; Jiang, B.; Wang, S.-
L.; Tu, S.-J. Org. Biomol. Chem. 2013, 11, 2417−2420.
(5) (a) Fox, H. H.; Lewis, J. I.; Wenner, W. J. Org. Chem. 1951, 16,
1259−1270. (b) Fuson, R. C.; Miller, J. J. J. Am. Chem. Soc. 1957, 79,
3477−3480. (c) Rebstock, A.-S.; Mongin, F.; Trecourt, F.; Queguiner,
G. Tetrahedron 2003, 59, 4973−4977. (d) Alessi, M.; Larkin, A. L.;
Ogilvie, K. A.; Green, L. A.; Lai, S.; Lopez, S.; Snieckus, V. J. Org.
Chem. 2007, 72, 1588−1594. (e) Shimada, K.; Takata, Y.; Osaki, Y.;
Moro-oka, A.; Kogawa, H.; Sakuraba, M.; Aoyagi, S.; Takikawa, Y.;
Ogawa, S. Tetrahedron Lett. 2009, 50, 6651−6653.
(6) Marquise, N.; Harford, P. J.; Chevallier, F.; Roisnel, T.; Dorcet,
V.; Gagez, A.-L.; Sable, S.; Picot, L.; Thiery, V.; Wheatley, A. E. H.;
Gros, P. C.; Mongin, F. Tetrahedron 2013, 69, 10123−10133.
(7) Kyba, E. P.; Liu, S.-T.; Chockalingam, K.; Reddy, B. R. J. Org.
Chem. 1988, 53, 3513−3521.
(8) Hundsdorf, T.; Blyumin, E. V.; Neunhoeffer, H. Synthesis 2002,
2532−2536.
(9) Fogagnolo, M.; Giovannini, P. P.; Guerrini, A.; Medici, A.;
Pedrini, P.; Colombi, N. Tetrahedron: Asymmetry 1998, 9, 2317−2327.
(10) Dominguez, E.; Ibeas, E.; Martinez de Marigorta, E.; Palacios, J.
K.; SanMartin, R. J. Org. Chem. 1996, 61, 5435−5439.
(11) Nunes, C. M.; Reva, I.; Fausto, R. J. Org. Chem. 2013, 78,
10657−10665.
(12) Pusch, S.; Opatz, T. Org. Lett. 2014, 16, 5430−5433.
(13) (a) She, Z.; Niu, D.; Chen, L.; Gunawan, M. A.; Shanja, X.;
Hersh, W. H.; Chen, Y. J. Org. Chem. 2012, 77, 3627−3633. (b) Yang,
D.; Burugupalli, S.; Daniel, D.; Chen, Y. J. Org. Chem. 2012, 77, 4466−
4472. (c) Long, Y.; She, Z.; Liu, X.; Chen, Y. J. Org. Chem. 2013, 78,
2579−2588.
(14) The structure of 2a was confirmed by single-crystal X-ray
(15) For an example of butylation of phenols by n-Bu4NBr, see:
In conclusion, we have developed a new synthetic approach
for 2-azafluorenones involving a tandem palladium-catalyzed
Heck/Heck-rearrangement reaction from halogen-substituted
isoxazoles and Michael acceptors. To the best of our
knowledge, this is the first example of a palladium-catalyzed
ring-opening reaction of isoxazoles. A key intermediate,
indenoisoxazolylidene-N,N-dimethylacetamide 6a, was success-
fully synthesized and converted to the final product, 2-
azafluorenone 2d, under the described optimal reaction
conditions. Further investigations incorporating palladium-
mediated ring opening reactions of isoxazoles in tandem
catalysis and their applications in the synthesis of compounds
with new chemical frameworks are underway in our laboratory
and will be reported in due course.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
X-ray crystallographic data for 2a (CIF)
X-ray crystallographic data for 10 (CIF)
Experimental procedures, spectral data, and copies of 1H
and 13C NMR spectra for all new compounds (PDF)
́
Balint, E.; Greiner, I.; Keglevich, G. Lett. Org. Chem. 2011, 8, 22−27.
AUTHOR INFORMATION
(16) It is also possible that the palladium−nitrogen bond in
intermediate 8 is protonated first to give the NH imine, which then
undergoes direct intramolecular condensation with the pendant
carbonyl group to give product 2.
■
Corresponding Author
Present Address
†Z.S.: School of Chemistry and Chemical Engineering, Sun Yat-
sen University, Guangzhou 510275, People’s Republic of
China.
(17) The structures of these intermediate compounds were
1
determined by H and 13C NMR spectroscopy and high-resolution
mass spectrometry. The E and Z isomers were determined by nuclear
Overhauser effect spectroscopy (for details, see the Supporting
(18) Two control experiments were carried out to estimate the extent
of Pd(II) catalysis. In the absence of a palladium catalyst, product 2d
was isolated in 32% yield after 4 h, and 26% of starting material 6a was
recovered after column chromatography. On the other hand, when
Pd2(dba)3 was employed as the catalyst, product 2d was isolated in
51% yield after 4 h, and 24% of starting material 6a was recovered after
column chromatography. These facts suggest the presence of a slower
rearrangement pathway that is not catalyzed by Pd(II), with the
possible adventitious oxidation of Pd(0) from Pd2(dba)3 to Pd(II) to
account for the higher yield in that control reaction.
(19) The structure of 10 was confirmed by single-crystal X-ray
(20) For a review of halide effects in transition-metal catalysis, see:
Fagnou, K.; Lautens, M. Angew. Chem., Int. Ed. 2002, 41, 26−47.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The work is dedicated to the memory of Professor Robert
Bittman at Queens College. We thank Queens College and the
City University of New York for financial support. Mass spectra
were recorded at the Mass Spectrometry Facilities in the
Chemistry Departments at North Carolina State University and
New York University. We thank Ms. Danielle Lehman at North
Carolina State University and Dr. Chin H. Lin at New York
University for their help in recording the mass spectra.
REFERENCES
■
(1) For reviews, see: (a) Fogg, D. E.; dos Santos, E. N. Coord. Chem.
Rev. 2004, 248, 2365−2379. (b) Wasilke, J.-C.; Obrey, S. J.; Baker, R.
T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001−1020. (c) Shindoh, N.;
Takemoto, Y.; Takasu, K. Chem. - Eur. J. 2009, 15, 12168−12179.
(2) For recent examples, see: (a) Li, L.; Herzon, S. B. Nat. Chem.
2014, 6, 22−27. (b) Chen, Q.-A.; Cruz, F. A.; Dong, V. M. J. Am.
Chem. Soc. 2015, 137, 3157−3160.
D
Org. Lett. XXXX, XXX, XXX−XXX