2
a,d
and agrochemical2d,e fields
Addition of Trifluoromethyltrimethylsilane to
Acyl Phosphonates: Synthesis of TMS-Protected
not only in the pharmaceutical
but also for material design.
2
e,f
4
Trifluoromethylation using Ruppert-Prakash reagent is one
of the most widely used methods to incorporate a trifluoromethyl
1-Alkyl-1-trifluoromethyl-1-hydroxyphosphonates
and 1-Aryldifluoroethenyl Phosphates
5
6
moiety into organic molecules. Prakash et al. carried out
extensive studies to develop varieties of easily accessible
nucleophilic catalysts to promote such reactions. TMS-protected
trifluoromethylated alcohols were prepared from both aldehydes
and ketones in excellent yields using a catalytic amount of amine
N-oxide. Carbonate and phosphate salts also showed efficient
Ayhan S. Demir* and Serkan Eymur
Department of Chemistry, Middle East Technical UniVersity,
0
6531 Ankara, Turkey
4
b
catalytic activity toward this reaction. This reagent was also
7
used for the effective formation of difluoroenol silyl ethers.
These enoxysilanes were also synthesized by Portella et al.8
starting from trifluoromethyltrimethylsilane and acylsilanes via
the Brook rearrangement of the alcohol adduct. Several ap-
proaches to difluoroenol silyl ethers have appeared in the
ReceiVed May 2, 2007
8
literature. Ishihara et al. prepared them by silylation of a zinc
difluoroenolate derived from chlorodifluoromethyl ketone.9
Other approaches, based on intermediate trialkylsilyltrifluorom-
ethyl carbinolate adducts, used silyllithium reagents either to
1
0
prepare a needed trifluoroacetylsilane or to add to a trifluo-
romethyl ketone. In situ silylation of a difluoroenolate obtained
by electroreduction of a trifluoromethyl ketone has also been
11
Addition reactions of nucleophilic CF
phonates were investigated. Various acyl phosphonates
reacted readily with CF TMS in the presence of K CO in
3
TMS to acyl phos-
1
2
reported.
Recently, we and others13 have shown that acyl phosphonates
are potent acyl anion precursors and undergo nucleophile-
promoted phosphonate-phosphate rearrangement to provide the
corresponding acyl anion equivalents as reactive intermediates.
Acyl phosphonates 1, which are easily synthesized from acyl
chloride and trialkyl phosphite in high yields, as the acyl anion
precursors, and aldehydes as the electrophiles in the presence
of a cyanide catalyst provide cross-benzoin products. Aromatic-
aromatic cross-benzoin synthesis, benzoyl phosphonates with
3
2
3
DMF at rt to give 1-alkyl-2,2,2-trifluoro-1-trimethylsily-
loxyethylphosphonate in 70-90% yields. When benzoyl
phosphonates were used as starting material, after addition
of CF , the formed alcoholate undergoes phosphonate-
3
phosphate rearrangement to form the acyl anion, followed
-
by elimination of F to give 1-aryldifluoroethenyl phosphates
in 87-97% yields. As a representative example, vinylphos-
phate 6a was converted into 2,2-difluoro-1-phenylethanone
7
8
with 6 N HCl/EtOH/reflux or CAN/NaOH/MeOH/0 °C in
2-90% yields.
(
4) (a) Ruppert, I.; Schlich, K.; Volbach, W. Tetrahedron Lett. 1984,
24, 2195. (b) Prakash, G. K. S.; Panja, C.; Vaghoo, H.; Surampudi, V.;
Kultyshev, R.; Mandal, M.; Rasul, G.; Mathew, T.; Olah, G. A. J. Org.
Chem. 2006, 71, 6806.
(
5) (a) Langlois, B. R.; Billard, T.; Roussel, S. J. Fluorine Chem. 2005,
26, 173. (b) Roussel, S.; Billard, T.; Langlois, B. R.; Saint-James, L. Chem.
Eur. J. 2005, 11, 939. (c) Ma, J. A.; Cahard, D. Chem. ReV. 2004, 104,
119. (d) Kim, J.; Shreeve, J. M. Org. Biomol. Chem. 2004, 2, 2728. (e)
1
Organofluorine compounds exhibit unique properties which
1
2
are of great interest in a wide range of applications and justify
the steadily growing number of new organofluorine products
which appear every year. Thus, these molecules are very useful
6
3
Massicot, F.; Monnier-Benoit, N.; Deka, N.; Plantier-Royon, R.; Portella,
C. J. Org. Chem. 2007, 72, 1174.
(
6) (a) Prakash, G. K. S.; Krishnamurati, R.; Olah, G. A. J. Am. Chem.
(
1) (a) Kirsch, P. Modern Fluoroorganic Chemistry; Wiley-VCH:
Soc. 1989, 111, 393. (b) Prakash, G. K. S.; Ramaiah, R. Synlett 1991, 643.
(c) Prakash, G. K. S.; Yudin, A. K. Chem. ReV. 1997, 97, 757. (d) Prakash,
G. K. S.; Mandal, M.; Schweizer, S.; Petasis, N. A.; Olah, G. A. Org. Lett.
2000, 2, 3173.
(7) (a) Uneyama, K.; Tanaka, H.; Kobayashi, S.; Shioyama, M.; Amii,
H. Org. Lett. 2004, 6, 2733. (b) Ishihara, T.; Yamana, M.; Ando, T.
Tetrahedron Lett. 1983, 24, 5657.
(8) (a) Portella, C.; Brigaud, T.; Lefebvre, O.; Plantier-Royon, R. J.
Fluorine Chem. 2000, 101, 193. (b) Lefebvre, O.; Brigaud, T.; Portella, C.
J. Org. Chem. 2001, 66, 1941. (c) Garayt, M. R.; Percy, J. M. Tetrahedron
Lett. 2001, 42, 6377.
Weinheim, Germany, 2004. (b) Chambers, R. D. Fluorine in Organic
Chemistry; Blackwell: Oxford, 2004. (c) Liebman, J. F., Greenberg, A.,
Dolbier, W. R., Jr., Eds. Fluorine Containing Molecules: Structure,
ReactiVity, Synthesis, and Applications; VCH: New York, 1988. (d) Large-
Radix, S.; Billard, T.; Langlois, B. R. J. Fluorine Chem. 2003, 124, 147.
e) Stahly, G. P.; Bell, D. R. J. Org. Chem. 1989, 54, 2873. (f) Thayer, A.
M. Chem. Eng. News 2006, June 5, 15. (g) Smart, B. E. J. Fluorine Chem.
001, 109, 3. (g) Uneyama, K. Organofluorine Chemistry; Blackwell:
Oxford, 2006.
(
2
(2) (a) Filler, R.; Kobayashi, Y.; Yagulpolskii, L. M. Organofluorine
compounds in- Medicinal Chemistry and Biomedical Applications; Elsevier,
Amsterdam, 1993. (b) Welch, J. T., Ewarakrishnan, S. E. Fluorine in
Bioorganic Chemistry; Wiley: New York, 1991. (c) Kukhar, V. P.;
Soloshonok, V. A. Fluorine-containing amino acids: Synthesis and
Properties; Wiley: Chichester, 1995. (d) Becker, A. InVentory of Industrial
Fluoro-Biochemicals; Eyrolles: Paris, 1996. (e) Banks, R. E.; Smart, B.
E.; Tatlow, J. C. Organofluorine Chemistry: Principles and Commercial
Applications; Plenum Press: New York, 1994. (f) Hiyama, T. Organof-
luorine Compounds: Chemistry and Properties; Springer-Verlag: Berlin,
(9) (a) Ishihara, T.; Yamana, M.; Maekawa, T.; Kuroboshi, M.; Ando,
T. J. Fluorine Chem. 1988, 38, 263. (b) Yamana, M.; Ishihara, T.; Ando,
T. Tetrahedron Lett. 1983, 24, 507.
(10) Jin, F.; Jiang, B.; Xu, Y. Tetrahedron Lett. 1992, 33, 1221.
(11) Fleming, I.; Roberts, R. S.; Smith, S. C. J. J. Chem. Soc., Perkin
Trans. 1 1998, 3741
(12) Uneyama, K.; Maeda, K.; Kato, T.; Katagiri, T. Tetrahedron Lett.
1998, 39, 3741.
(13) (a) Demir, A. S.; Reis, O.; Igdir, A. C.; Esiringu, I.; Eymur, S. J.
Org. Chem. 2005, 70, 10584. (b) Bausch, C. C.; Johnson, J. S. AdV. Synth.
Catal. 2005, 347, 1207.
2
000.
3) Schofield, H. J. Fluorine Chem. 1999, 100, 7.
(
1
0.1021/jo070913c CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/02/2007
J. Org. Chem. 2007, 72, 8527-8530
8527