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P.-L. Shao et al. / Tetrahedron Letters 51 (2010) 2316–2318
led to product in low yield with poor enantioselectivity (entry 15).
The enantioselectivities could be improved by lowering reaction
temperature to 0 °C for most cases except for reactions of ketenes
5c, 5f, and 5h (entries 3, 6, and 8).12
In summary, chiral N-heterocyclic carbenes were found to be
efficient catalysts for the formal [4+2] cycloaddition reaction of
alkyl(aryl)ketenes and 9,10-phenanthrenequinone to give the cor-
responding cycloadducts in good yields with highly enantioselec-
tivities. Further exploration on the enantioselective formal
cycloaddition reactions of ketenes is underway in our laboratory.
Supplementary data
Supplementary data (experimental procedures and compounds
characterization13) associated with this article can be found, in the
References and notes
1. (a) Tidwell, T. T. Ketenes, second ed.; John Wiley & Sons: Hoboken, New Jersey,
2006; (b) Tidwell, T. T. Angew. Chem., Int. Ed. 2005, 44, 5778; (c) Tidwell, T. T.
Eur. J. Org. Chem. 2006, 563; (d) Orr, R. K.; Calter, M. A. Tetrahedron 2003, 59,
3545; (e) Pall, D. H.; Weatherwax, A.; Lectka, T. Tetrahedron 2009, 65, 6771.
2. Wynberg, H.; Staring, E. G. J. J. Am. Chem. Soc. 1982, 104, 166.
3. (a) Bekele, T.; Shah, M. H.; Wolfer, J.; Abraham, C. J.; Weatherwax, A.; Lectka, T.
J. Am. Chem. Soc. 2006, 128, 1810; (b) Abraham, C. J.; Paull, D. H.; Scerba, M. T.;
Grebinski, J. W.; Lectka, T. J. Am. Chem. Soc. 2006, 128, 13370; (c) Wolfer, J.;
Bekele, T.; Abraham, C. J.; Dogo-Isonagie, C.; Lectka, T. Angew. Chem., Int. Ed.
2006, 45, 7398; (d) Xu, X.; Wang, K.; Nelson, S. G. J. Am. Chem. Soc. 2007, 129,
11690.
4. For the reviews of NHC-catalyzed reactions, see: (a) Enders, D.; Niemeier, O.;
Henseler, A. Chem. Rev. 2007, 107, 5606; (b) Marion, N.; Díez-González, S.;
Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2988; (c) Zeitler, K. Angew. Chem.,
Int. Ed. 2005, 44, 7506; (d) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37,
534.
5. (a) Zhang, Y.-R.; He, L.; Wu, X.; Shao, P.-L.; Ye, S. Org. Lett. 2008, 10, 277; (b)
Duguet, N.; Campbell, C. D.; Slawin, A. M. Z.; Smith, A. D. Org. Biomol. Chem.
2008, 6, 1108; (c) He, L.; Lv, H.; Zhang, Y.-R.; Ye, S. J. Org. Chem. 2008, 73, 8101;
(d) Huang, X.-L.; He, L.; Shao, P.-L.; Ye, S. Angew. Chem., Int. Ed. 2009, 48, 192; (e)
Lv, H.; You, L.; Ye, S. Adv. Synth. Catal. 2009, 351, 2822.
6. (a) Lin, Y.-M.; Boucau, J.; Li, Z.; Casarotto, V.; Lin, J.; Nguyen, A. N.; Ehrmantrau,
J. Org. Lett. 2007, 9, 567; (b) Nelson, S. G.; Zhu, C.; Shen, X. J. Am. Chem. Soc.
2004, 126, 14; (c) Shen, X.; Wasmuth, A. S.; Zhao, J.; Zhu, C.; Nelson, S. G. J. Am.
Chem. Soc. 2006, 128, 7438; (d) Nelson, S. G.; Wan, Z. Org. Lett. 2000, 2, 1883; (e)
Zhu, C.; Shen, X.; Nelson, S. G. J. Am. Chem. Soc. 2004, 126, 5352; (f) Calter, M. A.;
Tretyak, O. A.; Flashchenriem, C. Org. Lett. 2005, 1809.
3. Experimental section
3.1. Typical procedure for the [4+2] cycloaddition of ketenes
with 9, 10-phenanthrenequinone catalyzed by NHC
To an oven-dried 50 mL Schlenk tube equipped with a stir bar
was charged with trazolium salt 2c (36.4 mg, 0.05 mmol) and
anhydrous Cs2CO3 (16.3 mg, 0.05 mmol). This tube was closed with
a septum, evacuated, and back-filled with argon. To this mixture
was added freshly distilled toluene (4 mL) and stirred for 20 min
at room temperature. 9,10-Phenanthrenequinone
0.5 mmol) was added in one portion, and ethyl(phenyl)ketene 5a
(58.5 mg, 64 L, 0.4 mmol) was added via a syringe in three por-
8 (104 mg,
l
tion (3 ꢁ 0.4 mmol) in every 1 h. After the full conversion of
9,10-phenanthrenequinone, the reaction mixture was concen-
trated under reduced pressure and the residue was purified by
flash column chromatography to give cycloadduct 9a in 95% yield.
White solid, Rf = 0.5 (petroleum ether/ethyl acetate = 20:1); mp
152–154 °C; ½a 2D0
ꢂ
ꢀ146.2 (c 1, CHCl3); 1H NMR (300 MHz, CDCl3)
7. For the enantioselective reactions of disubstituted ketenes catalyzed by DMAP
derivatives, see: (a) Fu, G. C. Acc. Chem. Res. 2004, 37, 542; (b) Hodous, B. L.;
Ruble, J. C.; Fu, G. C. J. Am. Chem. Soc. 1999, 121, 2637; (c) Lee, E. C.; Hodous, B.
L.; Bergin, E.; Shih, C.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 11586; (d) Dochnahl,
M.; Fu, G. C. Angew. Chem., Int. Ed. 2009, 48, 2391.
d 8.63–8.61 (d, J = 8.1 Hz, 1H), 8.58–8.55 (d, J = 9.1 Hz, 1H), 8.49–
8.46 (d, J = 7.9 Hz, 1H), 8.14–8.10 (m, 1H), 7.80–7.75 (m, 1H),
7.72–7.66 (m, 1H), 7.62–7.53 (m, 2H), 7.48–7.45 (m, 2H), 7.24–
7.17 (m, 3H), 2.68–2.56 (m, 1H), 2.45–2.33 (m, 1H), 1.23–1.18 (t,
J = 7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 164.9, 137.0, 133.0,
131.6, 128.8, 128.7, 128.4, 127.4, 127.3, 126.7, 125.8, 125.0,
124.9, 123.6, 122.9, 122.6, 121.5, 120.4, 84.4, 33.9, 8.21; IR (KBr)
8. For the Synthesis and application of
a-hydroxy acid derivatives, see: (a)
Coppola, G. M.; Schuster, H. F. -Hydroxy Acids in Enantioselective Synthesis;
a
VCH: Weinheim, Germany, 1997; (b) Davis, F. A.; Chen, B.-C. Chem. Rev. 1992,
92, 919; (c) Janey, J. M. Angew. Chem., Int. Ed. 2005, 44, 4292; (d) Momiyama, N.;
Yamamoto, H. J. Am. Chem. Soc. 2003, 125, 6038.
9. The bases, such as cesium carbonate, were found to be able to promote the
cycloaddition reaction themselves. Thus the mixture of azolium salt and base
was stirred for 20–60 min to make the full consumption of the base before the
addition of substrates.
10. The enantioselectivity switch for cycloaddition reaction of ketenes and
N-benzoyldiazenes catalyzed by NHC was reported in our previous
publication (Ref. 5d).
v
3065, 2978, 1772 (s, C@O), 1338, 1132, 755, 723; EIMS m/z:
354 (20), 146 (100); HRMS-(EI) (m/z): M+ calcd for C24H18O3,
354.1256; found 354.1259; HPLC analysis: 91% ee [Daicel Chir-
alpak OD-H column; 20 °C, 254 nm, 1.0 mL/min; solvent system:
2-propanol/hexane = 10:90; retention times: 5.4 min (major),
12.4 min (minor)].
11. The reaction of ketene 5a and o-benzoquinone catalyzed by NHC 1a0 gave a
complex at room temperature, and no reaction occurred at ꢀ78 °C.
12. The reaction of (3-chlorophenyl)ethylketene (5f) at 0 °C went very slowly and
it took 48 h instead of 2–8 h for other reactions. In this case, most of
cycloadduct 9f may be generated via the uncatalyzed or cesium carbonate-
promoted reaction, and thus led to the extremely low ee for the whole reaction.
13. CCDC 754902 contains the Supplementary data for cycloadduct 9b in
this Letter. These data can be obtained free of charge from The
Acknowledgments
Financial support from National Science Foundation of China
(20872143), the Ministry of Science and Technology of China
(2009ZX09501-018) and the Chinese Academy of Sciences is
greatly acknowledged.