2908
V. Pace et al.
FEATURE ARTICLE
perature and the mixture was then stirred for 10 min. The solution
was warmed at 0 °C and the reaction was stirred for 20 min. The re-
action was then cooled at –78 °C and a solution of 2.0 M BnMgCl
in THF (1.04 mL, 2.08 mmol, 2.0 equiv) was added dropwise over
10 min and stirred for a further 50 min. The reaction was quenched
with 0.5 M HCl (8 mL) and THF (8 mL). The biphasic system was
warmed at 65 °C leaving the flask open for 2 h. After extraction of
the organic phase with additional CH2Cl2 (10 mL), the combined
extracts were dried (Na2SO4), filtered, and the solvent removed un-
der reduced pressure to give crude 11. Chromatography (silica gel,
petroleum ether–EtOAc, 95:5) gave pure chloro ketone 1116a (152
mg, 87%) as a yellow oil.
IR (NaCl): 3082, 1737, 992, 897 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.38–7.23 (m, 5 H), 4.13 (s, 2 H),
3.91 (s, 2 H).
13C NMR (125 MHz, CDCl3): δ = 199.1, 132.8, 129.4, 128.9, 127.5,
47.7, 46.8.
(12) Liu, W.-B.; Chen, C.; Zhang, Q.; Zhu, Z.-B. Beilstein J. Org.
Chem. 2012, 8, 344.
(13) Wang, J.; Li, H.; Zhang, D.; Huang, P.; Wang, Z.; Zhang, R.;
Liang, Y.; Dong, D. Eur. J. Org. Chem. 2013, 5376.
(14) (a) Braun, M. In The Chemistry of Organolithium
Compounds; Rappoport, Z.; Marek, I., Eds.; John Wiley and
Sons: Chichester, 2004. (b) Siegel, H. Lithium
Halocarbenoids – Carbanions of High Synthetic Versatility,
In Topics in Current Chemistry; Vol. 106; Springer: Berlin,
1982, 55. (c) Capriati, V.; Florio, S. Chem. Eur. J. 2010, 16,
4152. (d) Pace, V. Aust. J. Chem. 2014, 67, 311.
(15) Köbrich, G.; Akhtar, A.; Ansari, F.; Breckoff, W. E.;
Büttner, H.; Drischel, W.; Fischer, R. H.; Flory, K.; Fröhlich,
H.; Goyert, W.; Heinemann, H.; Hornke, I.; Merkle, H. R.;
Trapp, H.; Zündorf, W. Angew. Chem., Int. Ed. Engl. 1967,
6, 41.
(16) (a) Tarhouni, R.; Kirschleger, B.; Rambaud, M.; Villieras, J.
Tetrahedron Lett. 1984, 25, 835. (b) Sadhu, K. M.;
Matteson, D. S. Tetrahedron Lett. 1986, 27, 795.
(c) Michnick, T. J.; Matteson, D. S. Synlett 1991, 631.
(d) Kapeller, D. C.; Hammerschmidt, F. J. Am. Chem. Soc.
2008, 130, 2329.
Anal. Calcd for C9H9ClO: C, 64.11; H, 5.38. Found: C, 64.29; H,
5.53.
Supporting Information for this article is available online
(17) (a) Concellón, J. M.; Cuervo, H.; Fernández-Fano, R.
Tetrahedron 2001, 57, 8983. (b) Pace, V.; Castoldi, L.;
Holzer, W. Adv. Synth. Catal. 2014, 356, 1761.
(c) Barluenga, J.; Llavona, L.; Bernad, P. L.; Concellón, J.
M. Tetrahedron Lett. 1993, 34, 3173. (d) Barluenga, J.;
Baragaña, B.; Concellón, J. M. J. Org. Chem. 1999, 64,
2843.
at
10.1055/s-00000084.SunpfgIpi
o
o
nr
i
References
(1) Contributed equally to the work.
(18) (a) Concellón, J. M.; Rodríguez-Solla, H.; Simal, C. Org.
Lett. 2008, 10, 4457. (b) Concellón, J. M.; Rodríguez-Solla,
H.; Bernad, P. L.; Simal, C. J. Org. Chem. 2009, 74, 2452.
(c) Bull, J. A.; Boultwood, T.; Taylor, T. A. Chem. Commun.
2012, 48, 12246. (d) Boultwood, T.; Affron, D. P.;
Trowbridge, A. D.; Bull, J. A. J. Org. Chem. 2013, 78, 6632.
(19) Barluenga, J.; Fernandez-Simon, J. L.; Concellón, J. M.;
Yus, M. J. Chem. Soc., Perkin Trans. 1 1989, 77.
(20) (a) Barluenga, J.; Baragaña, B.; Alonso, A.; Concellón, J. M.
J. Chem. Soc., Chem. Commun. 1994, 969. (b) Barluenga, J.;
Baragaña, B.; Concellón, J. M. J. Org. Chem. 1995, 60,
6696. (c) Barluenga, J.; Baragaña, B.; Concellón, J. M.;
Piñera-Nicolás, A.; Díaz, M. R.; García-Granda, S. J. Org.
Chem. 1999, 64, 5048. (d) Kowalski, C. J.; Reddy, R. E.
J. Org. Chem. 1992, 57, 7194.
(21) Pace, V.; Holzer, W.; Verniest, G.; Alcántara, A. R.; De
Kimpe, N. Adv. Synth. Catal. 2013, 355, 919.
(22) Boche, G.; Lohrenz, J. C. W. Chem. Rev. 2001, 101, 697.
(23) Schäfer, G.; Matthey, C.; Bode, J. W. Angew. Chem. Int. Ed.
2012, 51, 9173.
(24) (a) Sleebs, B. E.; Hughes, A. B. J. Org. Chem. 2007, 72,
3340. (b) Kimmerlin, T.; Seebach, D. Helv. Chim. Acta
2003, 86, 2098.
(25) (a) Zhang, Y.; Wang, J. Chem. Commun. 2009, 0, 5350.
(b) Podlech, J. In Enantioselective Synthesis of β-Amino
Acids; Juaristi, E.; Soloshonok, V. A., Eds.; John Wiley &
Sons: New York, 2005. (c) Bernardim, B.; Pinho, V. D.;
Burtoloso, A. C. B. J. Org. Chem. 2012, 77, 9926.
(26) Hughes, A. B.; Sleebs, B. E. Synth. Commun. 2008, 39, 48.
(27) Cahiez, G.; Normant, J. F. Tetrahedron Lett. 1977, 18, 3383.
(28) (a) Saraireh, I. A. M. Tetrahedron Lett. 2012, 53, 2023.
(b) Hughes, A. B.; Sleebs, B. E. Aust. J. Chem. 2008, 61,
131.
(29) Plucińska, K.; Liberek, B. Tetrahedron 1987, 43, 3509.
(30) Pace, V.; Castoldi, L.; Holzer, W. Chem. Commun. 2013, 49,
8383.
(31) (a) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22,
3815. (b) Balasubramaniam, S.; Aidhen, I. S. Synthesis
(2) Concellón, J. M.; Bardales, E. Eur. J. Org. Chem. 2004,
1523.
(3) (a) Gunnlaugsson, T.; MacDónaill, D. A.; Parker, D. J. Am.
Chem. Soc. 2001, 123, 12866. (b) Harte, A. J.;
Gunnlaugsson, T. Tetrahedron Lett. 2006, 47, 6321.
(4) (a) Fujii, I.; Tanaka, F.; Miyashita, H.; Tanimura, R.;
Kinoshita, K. J. Am. Chem. Soc. 1995, 117, 6199.
(b) Renslo, A. R.; Jaishankar, P.; Venkatachalam, R.;
Hackbarth, C.; Lopez, S.; Patel, D. V.; Gordeev, M. F.
J. Med. Chem. 2005, 48, 5009.
(5) (a) Davies, D. T.; Kapur, N.; Parsons, A. F. Tetrahedron
Lett. 1999, 40, 8615. (b) Ishibashi, H.; Haruki, S.;
Uchiyama, M.; Tamura, O.; Matsuo, J.-i. Tetrahedron Lett.
2006, 47, 6263.
(6) (a) Voloshchuk, N.; Lee, M. X.; Zhu, W. W.; Tanrikulu, I.
C.; Montclare, J. K. Bioorg. Med. Chem. Lett. 2007, 17,
5907. (b) Wang, Z.; Li, F.; Zhao, L.; He, Q.; Chen, F.;
Zheng, C. Tetrahedron 2011, 67, 9199.
(7) Yang, Y.; Shang, P.; Cheng, C.; Wang, D.; Yang, P.; Zhang,
F.; Li, T.; Lu, A.; Zhao, Y. Eur. J. Med. Chem. 2010, 45,
4300.
(8) (a) Paczal, A.; Bényei, A. C.; Kotschy, A. J. Org. Chem.
2006, 71, 5969. (b) Morimoto, H.; Fujiwara, R.; Shimizu,
Y.; Morisaki, K.; Ohshima, T. Org. Lett. 2014, 16, 2018.
(c) Hodgson, D. M.; Labande, A. H.; Muthusamy, S. Org.
React. 2013, 80, 133–496.
(9) (a) Jung, J.-W.; Shin, D.-Y.; Seo, S.-Y.; Kim, S.-H.; Paek,
S.-M.; Jung, J.-K.; Suh, Y.-G. Tetrahedron Lett. 2005, 46,
573. (b) Pace, V.; Castoldi, L.; Holzer, W. J. Org. Chem.
2013, 78, 7764. (c) Murai, T.; Mutoh, Y. Chem. Lett. 2012,
41, 2.
(10) (a) Liu, W.; Hua, J.; Zhou, J.; Zhang, H.; Zhu, H.; Cheng, Y.;
Gust, R. Bioorg. Med. Chem. Lett. 2012, 22, 5008. (b) Ma,
L.; Chen, J.; Liang, X.; Xie, C.; Deng, C.; Huang, L.; Peng,
A.; Wei, Y.; Chen, L. Arch. Pharm. (Weinheim, Ger.) 2012,
345, 517.
(11) Stephen, A.; Schulz, G.; Reinshagen, H. Justus Liebigs Ann.
Chem. 1974, 363.
Synthesis 2014, 46, 2897–2909
© Georg Thieme Verlag Stuttgart · New York