Communication
ChemComm
(d) R. S. Dhiman, L. G. Opinska and R. Kluger, Org. Biomol. Chem.,
2011, 9, 5645; (e) Q.-L. Luo, L. Lv, Y. Li, J.-P. Tan, W. Nan and Q. Hui,
Eur. J. Org. Chem., 2011, 6916; ( f ) M. Pal and S. L. Bearne, Org.
Biomol. Chem., 2014, 12, 9760; (g) R. Kluger and L. L. Cameron,
J. Am. Chem. Soc., 2002, 124, 3303.
3 The following report indicates the intermediacy of acyl phosphate in
the reaction pathway of polyphosphoric acid: Y.-H. So and
J. P. Heeschen, J. Org. Chem., 1997, 62, 3552.
4 (a) W. W. Krajewski, T. A. Jones and S. L. Mowbray, Proc. Natl. Acad.
Sci. U. S. A., 2005, 102, 10499; (b) H. S. Gill, G. M. U. Pfluegl and
D. Eisenberg, Biochemistry, 2002, 41, 9863; (c) C. Moreira, M. J.
Ramos and P. A. Fernandes, Chem. – Eur. J., 2016, 22, 9218; (d) S.-
H. Liaw and D. Eisenberg, Biochemistry, 1994, 33, 675.
5 (a) A. J. Kirby, Acc. Chem. Res., 1997, 30, 290; (b) A. J. Kirby and
F. Noem, Acc. Chem. Res., 2015, 48, 1806.
Fig. 4 31P NMR spectral evidence for the intermediacy of acyl phosphate.
6 F. D. Popp and W. E. McEwen, Chem. Rev., 1958, 58, 321.
7 (a) P. E. Eaton, G. R. Carlson and J. T. Lee, J. Org. Chem., 1973,
38, 4071; (b) D. Zewge, C.-Y. Chen, C. Deer, P. G. Domer and D. L.
Hughes, J. Org. Chem., 2007, 72, 4276.
8 PPA or Eaton’s reagent is mainly used to build specific backbones,
such as 4-hydroxyquinolines8a, tetralones8b, and acridines8c. Inter-
molecular Friedel–Crafts reactions are mainly limited to simple
carboxylic acids8d. Recent applications to synthetic medicinal chem-
istry, see: (a) L. Tan, Z. Zhang, D. Gao, J. Luo, Z.-C. Tu, Z. Li, L. Peng,
X. Ren and K. Ding, J. Med. Chem., 2016, 59, 6807; (b) P. Mahalingam,
K. Takrouri, T. Chen, R. Sahoo, E. Papadopoulos, L. Chen, G. Wagner,
B. H. Aktas, J. A. Halperin and M. Chorev, J. Med. Chem., 2014,
Fig. 5 Acylation reaction of acyl phosphate (26).
This acyl phosphate (25) can generate the putative acylium
ion (23) or its equivalent, which reacts with aromatics (12) to
give aromatic ketones (15). A similar acyl phosphate can be
generated by a different method without using the acid: when
the sodium salt of phosphate diester (29) is mixed with benzoyl
chloride, acyl phosphate (26) is formed,2g as judged from
ESI-TOF measurements (Fig. 5). This acyl phosphate (26) can
react with benzene (12) in the presence of the acid (triflic acid)
to afford benzophenone (15) in 36% yield. This result supports
the idea that acyl phosphate is a good acylation agent for
benzene, probably because O–C bond cleavage of acyl phos-
phate (26) (and plausibly also 25) is energetically favored over
P–O bond cleavage upon protonation under strongly acidic
conditions, thus generating the acylium ion or its equivalent.
In summary, we present a chemoselective coupled reaction
in which the carbonyl functionality of carboxylic acids is
activated by a phosphate ester, followed by reaction of the
resulting acyl phosphate with benzenes to afford aromatic
ketones. The reaction conditions are compatible with various
other functional groups, including amines and esters. The
reaction mechanism of the phosphate ester and carboxylic acid
appears to involve both unimolecular and bimolecular reaction
pathways. A detailed study of the mechanism is in progress.
This research was partially supported by a Grant-in-Aid for
Research Fellowships for Young Scientists (JSPS) to A. S. (16J08260).
The computations were performed at the Research Center for
Computational Science, Okazaki (Japan).
´
57, 5094; (c) S. Montalvo-Quiros, A. Taladriz-Sender, M. Kaiser and
C. Dardonville, J. Med. Chem., 2015, 58, 1940; (d) D. Shi, J. Li, B. Jiang,
S. Guo, H. Su and T. Wang, Bioorg. Med. Chem. Lett., 2012, 22, 2827.
9 (a) T. Shioiri, K. Ninomiya and S. Yamada, J. Am. Chem. Soc., 1972,
94, 6203; (b) B. Castro, J. R. Dormoy, G. Evin and C. Selve, Tetra-
hedron Lett., 1975, 16, 1219.
10 These phosphorus reagents are employed as coupling reagents for
amide bond formation: E. Valeur and M. Bradley, Chem. Soc. Rev.,
2009, 38, 606.
11 D. A. Horton, G. T. Bourne and M. L. Smythe, Chem. Rev., 2003, 103, 893.
12 G. Sartori and R. Maggi, Chem. Rev., 2011, 111, PR181.
13 X.-F. Wu, H. Neumann and M. Beller, Chem. Soc. Rev., 2011, 40, 4986.
14 (a) O. Itoh, T. Honnami, A. Amano, K. Murata, Y. Koichi and
T. Sugita, J. Org. Chem., 1992, 57, 7334; (b) T. F. Buckley III and
H. Rapoport, J. Am. Chem. Soc., 1981, 103, 6157; (c) I. Ivanov,
S. Nikolova and S. Statkova-Abeghe, Synth. Commun., 2006, 36, 1405.
15 Amides,a,b,c nitriles,d and esterse can be used to generate acylium
ions: (a) E. K. Raja, D. J. DeSchepper, S. O. N. Lill and D. A. Klumpp,
J. Org. Chem., 2012, 77, 5788; (b) P.-Q. Huang, Y.-H. Huang and
K.-J. Xiao, J. Org. Chem., 2016, 81, 9020; (c) Y. Liu, G. Meng, R. Liu and
M. Szostak, Chem. Commun., 2016, 52, 6841; (d) M. Yato, T. Ohwada
and K. Shudo, J. Am. Chem. Soc., 1991, 113, 691; (e) J. P. Hwang,
G. K. S. Prakash and G. A. Olah, Tetrahedron, 2000, 56, 7199.
16 Representative reactions of carboxylic acids toward phosphate tri-
esters; (a) S. A. Khan and A. J. Kirby, J. Chem. Soc. B, 1970, 1172;
(b) N. Asaad and A. J. Kirby, J. Chem. Soc., Perkin Trans. 2, 2002, 1708.
17 Reports on the reactivity of (methyl) salicylate(s) containing phos-
phate esters: (a) R. H. Bromilow, S. A. Khan and A. J. Kirby, J. Chem.
Soc. B, 1971, 1091; (b) K. W. Y. Abell and A. J. Kirby, J. Chem. Soc.,
´
Perkin Trans. 2, 1983, 1171; (c) T. C. Bruice, A. Blasko and M. E.
Petyak, J. Am. Chem. Soc., 1995, 117, 12064.
18 Our findings on methyl salicylate as
a good leaving group:
(a) A. Sumita, Y. Otani and T. Ohwada, Org. Biomol. Chem., 2016,
14, 1680; (b) A. Sumita, H. Kurouchi, Y. Otani and T. Ohwada, Chem. –
Asian J., 2014, 9(10), 2995; (c) H. Kurouchi, A. Sumita, Y. Otani and
T. Ohwada, Chem. – Eur. J., 2014, 20, 8682.
19 Phosphate triesters possess high stability, and are often employed
as flame retardants. Representative paper: D. L. Biederman,
K. W. Hoffman, L. E. Todd and J. D. Koola, Phosphorus, Sulfur
Silicon Relat. Elem., 1999, 144, 29.
Notes and references
1 (a) F. H. Westheimer, Science, 1987, 235, 1173; (b) J. McMurry and
T. Begley, The Organic Chemistry of Biological Pathways, Roberts and 20 R. Rendy, Y. Zhang, A. McElrea, A. Gomez and D. A. Klumpp, J. Org.
Company Publishers, Englewood, Colorado, 2005. Chem., 2004, 69, 2340.
2 Reviews on the reactivity of acyl phosphate; R. Kluger, Synlett, 2000, 21 According to Olah and McFarland, the 31P NMR peaks of the
1708. Recent reports about the reactivity of acyl phosphate;
(a) T. P. Smyth and B. W. Corby, J. Org. Chem., 1998, 63, 8946;
protonated phosphate and neutral phosphate are not very different.
G. A. Olah and C. W. McFarland, J. Org. Chem., 1971, 36, 1374.
(b) S. Tzvetkova and R. Kluger, J. Am. Chem. Soc., 2007, 129, 15848; 22 M. J. Frisch, et al., Gaussian 09, revision D.01, Gaussian, Inc.,
(c) J. Wodzinska and R. Kluger, J. Org. Chem., 2008, 73, 4753;
Wallingford, CT, 2013.
Chem. Commun.
This journal is ©The Royal Society of Chemistry 2017