Environ. Toxicol. Chem., 2002, 21, 783; (c) E. Kraka and
D. Cremer, J. Am. Chem. Soc., 2000, 122, 8245; (d) C. H. Lin,
M. S. Lin, Y. H. Lin, I. M. Chen, P. R. Lin, C.-Y. Cheng and
M. C. Tsai, Pharmacology, 2003, 67, 202.
2 (a) D. B. MacLean, in The Alkaloids, ed. R. H. F. Manske,
Academic Press, New York, 1985; (b) M. Sharma, The Isoquinoline
Alkaloids, Chemistry and Pharmacology, Academic Press, New York,
1972; (c) T. Kametani, in The Total Synthesis of Natural Products,
ed. J. ApSimon, Wiley, New York, 1977, vol. 3, p. 4.
3 Selected examples: (a) A. P. Venkov and I. I. Ivanov, Tetrahedron,
1996, 52, 12299; (b) R. D. Larsen, R. A. Reamer, E. G. Corley,
P. Davies, E. G. Grabowaki, P. J. Reider and I. Shinkai,
Scheme 4
´
J. Org. Chem., 1991, 56, 6034; (c) L. Castedo, R. J. Estevez,
J. M. Saa and R. Suau, J. Heterocycl. Chem., 1982, 19, 1469;
heterocyclic species C, which can also be viewed as a penta-
dienyl cation with its resonance structure better represented by
benzyl cation C0; the corresponding cationic center is
stabilized by both benzene and nitrogen atoms. We envisage
that the neighboring cation of structure C0 facilitates the N–O
bond cleavage to give species D bearing both imine and ketene
functionalities. Species D is expected to be active toward
6p-electrocyclization to give observed 3(2H)-isoquinolone 3b.
Formation of a ketene intermediate via an intramolecular oxo
transfer to a tethered alkyne is very rare in literature reports.12
In summary, we report a new catalytic synthesis of
a-pyridones and isoquinolin-3(2H)-ones from readily available
3-en-5-ynyl nitrones and o-alkynylphenyl nitrones. This
ruthenium-catalyzed cycloisomerization is designed based on
a vinylidene route that was verified by deuterium labeling
experiments. The practicability of this new method is reflected
in its high cyclization efficiency and excellent chemoselectivity.
In contrast to reported syntheses,3 this method works equally
efficiently for electron-deficient 3(2H)-isoquinolones.
´
(d) N. J. McCorkindale and A. W. McCulloch, Tetrahedron, 1971,
27, 4653; (e) N. J. Mruk and H. Tieckelmann, Tetrahedron Lett.,
1970, 14, 1209; (f) D. W. Jones, J. Chem. Soc., 1969, 1729.
4 W. Eberbach and J. Roser, Tetrahedron Lett., 1987, 28, 2689.
5 W. Eberbach and N. Laber, Tetrahedron Lett., 1992, 33, 61.
6 R. S. Liu, Synlett, 2008, 801.
7 H.-S. Yeom, J.-E. Lee and S. Shin, Angew. Chem., Int. Ed., 2008,
47, 7040.
8 For TpRuPPh3(CH3CN)2SbF6-catalyzed carbocyclization of
terminal alkynes through a ruthenium-vinylidene intermediate,
see reference 6 and selected examples: (a) S. Datta, A. Odedra
and R.-S. Liu, J. Am. Chem. Soc., 2005, 127, 11606; (b) H.-C. Shen,
S. Pal, J.-J. Lian and R.-S. Liu, J. Am. Chem. Soc., 2003, 125,
15762.
9 Review: (a) C. Bruneau and P. H. Dixneuf, Angew. Chem., Int. Ed.,
´
2006, 45, 2176; (b) J. A. Varela and C. Saa, Chem.–Eur. J., 2006,
12, 6450; (c) B. M. Trost, Acc. Chem. Res., 2002, 35, 695;
(d) R.-S. Liu, in Metal Vinylidenes and Allenylidenes in Catalysis,
ed. C. Bruneau and P. H. Dixneuf, Wiley-VCH, Weinheim, 2008,
ch. 6, p. 193.
10 Crystallographic data of compound 5e (CCDC 734049) can be
obtained free of charge from the Cambridge Crystallographic Data
11 E. Bustelo, J. J. Carbo, A. Lledos, K. Mereiter, M. C. Puerta and
P. Valerga, J. Am. Chem. Soc., 2003, 125, 3311.
12 Previously, we observed formation of alkene–ketene species
through ruthenium-catalyzed coupling of epoxide–alkyne
functionality; see R. J. Madhushaw, M.-Y. Lin, S. M. Abu Sohel
and R.-S. Liu, J. Am. Chem. Soc., 2004, 126, 6895.
Notes and references
1 (a) R. M. Kanojia, J. B. Press, O. W. Lever, Jr., L. William,
J. J. McNally, A. J. Tobia, R. Falotico and J. B. Moore, Jr.,
J. Med. Chem., 1988, 31, 1363; (b) T. W. Schultz and G. D. Sinks,
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5233–5235 | 5235