Chemistry - An Asian Journal
10.1002/asia.201500308
COMMUNICATION
Carboxylic acid (1.0 mmol) in THF (3.0 ml) was added via a cannula, and
the reaction mixture was gradually warmed to the indicated temperature
and stirred for the indicated time. The reaction was quenched with
aqueous sat. NH4Cl, and the mixture was extracted with Et2O (3 × 15
mL). The combined organic layer was dried over MgSO4, filtered, and
concentrated under reduced pressure. The residue was purified by silica
gel flash column chromatography (eluent: hexane/Et2O) to afford the
desired methylketone. Method B: To a Schlenk tube charged with THF
(3.0 ml) were added Me2Zn (1.02 M heptane solution, 1.2 mmol) and
MeLi (1.17 M Et2O solution, LiBr free, 1.2 mmol) at 0 °C. The mixture
was stirred for 1 h at the indicated temperature to generate Me3ZnLi.
Lithium carboxylate was prepared by the reaction of carboxylic acid (1.0
mmol) and MeLi (1.17 M Et2O solution, 1.0 mmol) in THF (3.0 ml) for 1 h
at –78 °C in another Schlenk tube. The solution of Me3ZnLi was
transferred to the solution of lithium carboxylate dropwise via a cannula.
The resultant mixture was allowed to warm gradually to 50 °C and stirred
for the indicated time. Workup and purification were performed as
described for Method A.
of Friedel-Crafts acylation type reaction, see: M. C. Wilkinson, Org. Lett.
2011, 13, 2232.
[5]
After the seminal discovery by Gilman in 1933, this approach became
one of the most straightforward methods to access ketones. a) W. D.
Lubell, H. Rapoport, J. Am. Chem. Soc. 1988, 110, 7447; b) T. M. Bare,
H. O. House, Org. Synth. 1973, 5, 775; c) M. J. Jorgenson, Org. React.
1970, 18, 1; d) H., Gilman, P. R. van Ess, J. Am. Chem. Soc. 1933, 55,
1258; e) F. Alonso, E. Lorenzo, M. Yus, J. Org. Chem. 1996, 61, 6058;
f) R. Levine, M. J. Karten, W. M. Kadunce, J. Org.Chem. 1975, 40,
1770; g) G. M. Rubottom, C.-W. Kim, J. Org.Chem. 1983, 48, 1550.
Grignard reagents are generally not as effective as organolithiums for
this transformation. For a recent publication on addition reactions of
organomagnesium reagents to carboxylate salts, see: M. Ohki, M.
Asaoka, Chem. Lett. 2009, 38, 856;
[6]
[7]
[8]
D. T. Genna; G. H. Posner, Org. Lett. 2011, 13, 5358.
Selected publications on this topic, see: a) Y. Nagashima, R. Takita, K.
Yoshida, K. Hirano, M. Uchiyama, J. Am. Chem. Soc. 2013, 135,
18730; b) C. Wang, T. Ozaki, R. Takita, M. Uchiyama, Chem. Eur. J.,
2012, 18, 3482; c) M. Uchiyama, Y. Kobayashi, T. Furuyama, S.
Nakamura, Y. Kajihara, T. Miyoshi, T. Sakamoto, Y. Kondo, K.
Morokuma, J. Am. Chem. Soc., 2008, 130, 472; d) M. Uchiyama, Y.
Matsumoto, S. Usui, Y. Hashimoto, K. Morokuma, Angew. Chem., Int.
Ed, 2007, 46, 926; e) M. Uchiyama, T. Furuyama, M. Kobayashi, Y.
Matsumoto, K. Tanaka, J. Am. Chem. Soc., 2006, 128, 8404; f) S.
Nakamura, M. Uchiyama, T. Ohwada, J. Am. Chem. Soc., 2005, 127,
13116; g) S. Nakamura, M. Uchiyama, T. Ohwada, J. Am. Chem. Soc.,
2004, 126, 11146; h) M. Uchiyama, M. Kameda, O. Mishima, N.
Yokoyama, M. Koike, Y. Kondo, T. Sakamoto, J. Am. Chem. Soc., 1998,
120, 4934; i) M. Uchiyama, S. Furumoto, M. Saito, Y. Kondo, T.
Sakamoto, J. Am. Chem. Soc., 1997, 119, 11425.
Acknowledgements
This work was supported by JSPS KAKENHI (S) (No.
24229011), Takeda Science Foundation, The Asahi Glass
Foundation, Daiichi-Sankyo Foundation of Life Sciences,
Mochida Memorial Foundation, Tokyo Biochemical Research
Foundation, Foundation NAGASE Science Technology
Development, and Sumitomo Foundation (to M. U.), JSPS
Grant-in-Aid for Young Scientists (Start-up) (No. 24850005) and
JSPS Grant-in-Aid for Young Scientists (B) (No. 26860010) (to K.
H.) (No. 24850005). The calculations were performed on the
Riken Integrated Cluster of Clusters (RICC). We gratefully
[9]
J. Burdon, H. S. Gill, I. W. Parsons, J. C. Tatlow, J. Chem. Soc.,Chem.
Commun. 1979, 1147.
[10] M. Uchiyama, M. Koike, M. Kameda, Y. Kondo, T. Sakamoto, J. Am.
Chem. Soc., 1996, 118, 8733.
[11] Proposed simultaneous or consecutive double zincation.
acknowledge
Advanced
Center
for
Computing
and
Communication (RIKEN) for providing computational resources.
Keywords: ketone • carboxylic acid • organozincates •
chemoselective • DFT calculation
[12] For halogen-metal exchange-based double functionalization, see: C.
Despotopoulou, R. C. Bauer, A. Krasovskiy, P. Mayer, J. M. Stryker, P.
Knochel, Chem. Eur. J., 2008, 14, 2499.
[1]
[2]
a) B. M. Trost, Angew. Chem. Int. Ed. Engl. 1995, 34, 259; b) B. M.
Trost, Science 1991, 254, 1471.
[13] M. Isobe, S. Kondo, N. Nagasawa, T. Goto, Chem. Lett. 1977, 679.
[14] Y. Kondo, N. Takazawa, C. Yamazaki, T. Sakamoto, J. Org. Chem.
1994, 59, 4717.
a) P. A. Wender, M. P. Croatt, B. Witulski, Tetrahedron 2006, 62, 7505;
b) P. A. Wender, B. L. Miller, Nature 2009, 460, 197.
[3]
[4]
S. Nahm, S. M. Weinreb, Tetrahedron Lett. 1981, 22, 3815.
[15] For details, see Supporting Information.
Representative non-catalytic addition reactions of organometallics to
acid chlorides: Cu: a) G. H. Posner, C. E. Whitten, P. E. McFarland, J.
Am. Chem. Soc. 1972, 94, 5106; b) R. M. Wehmeyer, R. D. Rieke,
Tetrahedron Lett. 1988, 29, 4513; c) K. Takai, K. Oshima, H. Nozaki,
Bull. Chem. Soc. Jpn. 1981, 54, 1281; d) P. Knochel, M. C. P. Yeh, S.
C. Berk, J. Talbert, J. Org. Chem. 1988, 53, 2390. Mg: X. Wang, L.
Zhang, X. Sun, Y. Xu, D. Krishnamurthy, C. H. Senanayake, Org. Lett.
2005, 7, 5593. Also see references cited therein for catalytic and non-
catalytic transformations using various metal species. Recent example
[16] A series of heteroleptic triorganozincates was prepared and studied in
conjugate addition reactions by Oshima et al., see: W. Tückmantel, K.
Oshima, H. Nozaki, Chem. Ber. 1986, 119, 1581.
[17] (a) K. Fukui, Acc. Chem. Res. 1981, 14, 363. (b) K. Ishida, K.
Morokuma, A. Komornicki, J. Chem. Phys. 1977, 66, 2153. (c) C.
Gonzalez, H. B. Schlegel, J. Chem. Phys. 1989, 90, 2154. (d) H. B.
Schlegel, C. Gonzalez, J. Phys. Chem. 1990, 94, 5523.