798
H. Maekawa et al. / Tetrahedron Letters 51 (2010) 796–799
CF3
OTMS
Ph
OTMS
O
n-Bu4NF
EtO
HO
Ph CH Ph
CF3
Ph
TMSO
THF
Ph
6a
Ph
2a
O
O
OTMS
-
•
Mg (+e)
TMSCl
Scheme 4.
Ph
Ph
Ph
-
Ph
Ph
Mg (+e)
Ph
1a
CF
CF
Ph
3
3
Table 4
Desilylation of acetal
-
CF CO Et
TMSCl
EtO
TMSO
OTMS
Ph
EtO
O
3
2
Ph
TMSO
Entry
Ar
2
Yield (%) 6
Ph
2a
1
2
3
4
5
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
4-FC6H4
3-CH3C6H4
2b
2c
2d
2e
2f
6b
6c
6d
6e
6f
57
80
57
92
88
CF CO Et
3
2
Scheme 6.
Reaction conditions: 2 (2.5 mmol), n-Bu4NF (0.15–0.5 equiv mol), THF (20 ml), À10
to 5 °C, N2 atmosphere.
compounds at the carbonyl carbon atom of benzophenone in high
yield and the acetals can be easily converted into the corresponding
ketones. This trifluoroacetylation is a novel method for the introduc-
tion of trifluoroacetyl group through electron transfer.
C2F5
O
n-Bu4NF
HO
Ph
EtO
OTMS
Ph
Acknowledgment
C2F5
TMSO
THF
Ph
Ph
7a
4a
Authors thank Dr. Motoo Shiro, Rigaku Cooperation for X-ray
crystalline analysis of our product 2a.
Yield 80%
Scheme 5.
Supplementary data
Benzophenone showed more positive reduction potential than
ethyl trifluoroacetate26, while any significant reduction peak can-
not be detected for trifluoroacetic anhydride, trifluoroacetylimi-
dazole, and acetal 2a. Since the trifluoroacetylated compound 6a
showed the same reduction potential at À1.74 V versus Ag/AgCl
as the starting benzophenone 1a, 6a could be obtained in two steps
through the formation of the acetal 2a without easily reduced car-
bonyl group.
This reaction is initiated by one electron transfer from Mg to
benzophenone followed by the attack of trimethylchlorosilane
and ethyl trifluoroacetate to give the product 2 as shown in
Scheme 6.
Trifluoroacetic acid derivatives with a good leaving group, such
as phenyl trifluoroacetate, trifluoroacetic anhydride, and trifluoro-
acetylimidazole did not give the coupling compounds, and the re-
sult implies that this reaction depends on the nature of leaving
group of trifluoroacetic acid derivatives.27 Acetal 2a cannot be eas-
ily reduced owing to its more negative reduction potential under
the reaction conditions, therefore, ethyl trifluoroacetate might be
an excellent trifluoroacetylating reagent.
Supplementary data associated with this article can be found, in
References and notes
1. Hudlicky, M. Org. React. 1988, 35, 513.
2. Taylor, S. D.; Kotoris, C. C.; Hum, G. Tetrahedron 1999, 55, 12431. and references
cited therein.
3. Kitazume, T.; Yamazaki, T. Experimental Methods in Organic Fluorine Chemistry;
Kodansha: Tokyo, 1998.
4. Wiedemann, J.; Heiner, T.; Molston, G.; Prakash, G. K. S.; Olah, G. A. Angew.
Chem., Int. Ed. 1998, 37, 820.
5. Singh, R. P.; Cao, G.; Kirchmeier, R. L.; Shreeve, J. M. J. Org. Chem. 1999, 64, 2873.
6. Gassman, P. G.; O’Reilly, N. J. J. Org. Chem. 1987, 52, 2481.
7. Chang, Y.; Cai, C. J. Fluorine Chem. 2005, 126, 937.
8. Bégué, J. P.; Bonnet-Delpon, D. Tetrahedron 1991, 47, 3207. and references cited
therein.
9. Keumi, T.; Shimada, M.; Takahashi, M.; Kitajima, H. Chem. Lett. 1990, 783.
10. Moriguchi, T.; Endo, T.; Takata, T. J. Org. Chem. 1995, 60, 3523.
11. Kakino, R.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn. 2001, 74, 371.
12. Chen, L. S.; Chen, G. J.; Tamborski, C. J. Fluorine Chem. 1981, 18, 117.
13. Creary, X. J. Org. Chem. 1987, 52, 5026.
14. Villuendas, I.; Parrilla, A.; Guerrero, A. Tetrahedron 1994, 50, 12673.
15. Kerdesky, F. A. J.; Bahsa, A. Tetrahedron Lett. 1991, 32, 2003.
16. Guiles, J. W. Synlett 1995, 165.
As a summary, Mg-promoted reduction of benzophenones in the
presence of ethyl trifluoroacetate gave acetals of trifluoroacetylated
17. Nishiguchi, I.; Sakai, M.; Maekawa, H.; Ohno, T.; Yamamoto, Y.; Ishino, Y.
Tetrahedron Lett. 2002, 43, 635.
18. Ohno, T.; Sakai, M.; Ishino, Y.; Shibata, T.; Maekawa, H.; Nishiguchi, I. Org. Lett.
2001, 3, 3439.
19. Seebach, D.; Corey, E. J. J. Org. Chem. 1975, 40, 231.
Table 5
20. Nakamura, Y.; Uneyama, K. J. Org. Chem. 2007, 72, 5894.
21. Hosokawa, T.; Matsumura, A.; Katagiri, T.; Uneyama, K. J. Org. Chem. 2008, 73,
1468.
Reduction potential of reagents
O
22. General procedure for coupling reaction of benzophenone and ethyl trifluoroacetate: A
typical procedure is as follows. A solution containing TMSCl (20 mmol), ethyl
trifluoroacetate (55 mmol)in dry NMP (10 ml) is added to Mg turnings (10 mmol)
for Grignard reagent with no pre-treatment in a four-necked flask and after
30 min,asolutionofbenzophenone(5 mmol)inNMP(20 ml)wasaddeddropwise
at room temperature. The reaction mixture was stirred until benzophenone
disappeared by TLC monitoring. Then the reaction mixture was poured into
300 mlofasaturatedsodiumhydrogencarbonatesolutionandwasextractedwith
ethyl acetate. Usual work-up, subsequent silica gel column chromatography
and recrystallization with methanol gave 2-ethoxy-1,1,1-trifluoro-2,3-bis
(trimethylsiloxy)-3,3-diphenylpropane 2a in good yield.2-Ethoxy-1,1,1-trifluoro-
2,3-bis(trimethylsiloxy)-3,3-diphenylpropane (2a): 1H NMR (400 MHz, CDCl3) d
(ppm): À0.12 (9H, s), 0.16 (9H, s), 1.28 (3H, t, J = 7.1 Hz), 3.87–4.00 (2H, m), 7.23–
7.25 (6H, m), 7.48–7.54 (4H, m). 13C NMR (100 MHz, CDCl3) d (ppm): 1.74, 1.89,
À1.74 V
À1.74 V
CF3CO2Et
À2.47
Ph Ph
1a
CF3
O
(CF3CO)2O
—
HO Ph
Ph
6a
CF3
O
EtO OTMS
TMSO Ph
F3C
N
N
—
—
2a
Ph
Working electrode: Pt, counter electrode: Pt, reference electrode: Ag/AgCl, substrate
(7 mmol/l), solvent: NMP (15 ml), supporting electrolyte: 1% n-Bu4NClO4, scan rate:
200 mV/s.
2
1
15.48, 60.31 (m), 86.03, 100.70 (q, JCF = 26.6 Hz), 121.72 (q, JCF = 298.1 Hz),