New Polyfluorinated Organotin Reagents. Stereoselective Synthesis of (Z)-α-Fluoro-β-trifluoromethylvinylstannanes

Article abstract of DOI:10.1021/ol0200697

(Formula Presented) A new methodology for the synthesis of (Z)-α-fluoro-β-trifluoromethylvinylstannanes, which are useful polyfluorinated organotin reagents for the synthesis of fluorine-containing biologically active compounds, is described.

Full text of DOI:10.1021/ol0200697

ORGANIC
LETTERS
2
002
Vol. 4, No. 12
083-2085
New Polyfluorinated Organotin
Reagents. Stereoselective Synthesis of
2
(
Z)-r-Fluoro-â-trifluoromethylvinylstannanes
Yanchang Shen* and Guoping Wang
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Academia Sinica, 345 Linglin Lu, Shanghai 200032, China
shenyc@pub.sioc.ac.cn
Received April 4, 2002
ABSTRACT
A new methodology for the synthesis of (Z)-r-fluoro-â-trifluoromethylvinylstannanes, which are useful polyfluorinated organotin reagents for
the synthesis of fluorine-containing biologically active compounds, is described.
In the past several decades, much effort has been devoted
to introducing a fluorine or trifluoromethyl functionality into
organic molecules because of the dramatic effects of this
functionality on their structure stability, reactivity, and
Recently, the stereospecific synthesis of (E)- and (Z)-(1-
fluorovinyl)stannanes was reported and applied to the
5
synthesis of enzyme inhibitors containing 2-fluoro terminal
6
7
olefins. The synthesis of 1,2-difluorovinylstannanes and
1
biological activity of the resulting compounds. Fluorinated
organometallic reagents provide a useful and convenient
methodology for the introduction of fluorine or trifluorom-
ethyl functionality into organic molecules. Organotin com-
(
3) (a) Piers, E.; McEachern, E. J.; Romero, M. A. Tetrahedron Lett.
1
996, 37, 1173. (b) Paley, R. S.; de Dios, A.; Estroff, L. A.; Lafontaine, J.
2
A.; Montero, C.; McCulley, D. J.; Rubio, M. B.; Ventura, M. P.; Weers,
H. L.; Fernandezde la Pradilla, R.; Castro. S.; Dorado, R.; Morente, M. J.
Org. Chem. 1997, 62, 6326. (c) Kamlage, S.; Sefkow, M.; Peter, M. G. J.
Org. Chem. 1999, 64, 2938. (d) Ceccarelli, S.; Piarulli, U.; Gennari, C. J.
Org. Chem. 2000, 65, 6254. (e) Grasa, G. A.; Nolan, S. P. Org. Lett. 2001,
pounds are versatile reagents in synthetic organic chemistry.
Among them, vinylstannanes have attracted special attention
and emerged recently as highly valuable intermediates in
3
, 119.
3
organic synthesis. In particular, a number of complex
(4) (a) Nicolaou, K. C.; Chakraborty, T. K.; Piscopio, A. D.; Minowa,
N.; Bertinato, P. J. Am. Chem. Soc. 1993, 115, 4419. (b) Macdonald, G.;
Alcaraz, L.; Wei, X.; Lewis, N. J.; Taylor, R. J. K. Tetrahedron 1998, 54,
naturally occurring compounds have been synthesized by
using the Stille palladium-catalyzed coupling reaction of
9
823. (c) Paterson, I.; Lombart, H.-G.; Allerton, C. Org. Lett. 1999, 1, 19.
4
vinylstannanes which were employed as key intermediates.
(d) Chakraborty, T. K.; Thippeswamy, D. Synlett. 1999, 155. (e) Toshima,
K.; Jyojima, T.; Miyamoto, N.; Katkhno, M.; Nakata, M.; Matsumura, S.
J. Org. Chem. 2001, 66, 1705.
(
1) (a) Welch, J. T. Tetrahedron 1987, 43, 3123. (b) Welch, J. T.;
Eswarakrishnam, S. Fluorine in Biorganic Chemistry; Wiley: New York,
991. (c) Resnati, G. Tetrahedron 1993, 49, 9385. (d) Organofluorine
(5) (a) McCarthy, J. R.; Mattews, D. P.; Stemerick, D. M.; Huber, E.
W.; Bey, P.; Lipper, B. J.; Snyder, R. D.; Sunkara, P. S. J. Am. Chem. Soc.
1991, 113, 7439. (b) Moore, W. R.; Schatzman, G. L.; Jarvi, E. T.; Gross,
R. S.; McCarthy, J. R. J. Am. Chem. Soc. 1992, 114, 360. (c) Matthews, D.
P.; Millers, S. C.; Jarvi, E. T.; Sabol, J. S.; McCarthy, J. R. Tetrahedron
Lett. 1993, 34, 3057. (d) Gross, R. S.; Mehdi, S.; McCarthy, J. R.
Tetrahedron Lett. 1993, 34, 7197. (e) Matthews, D. P.; Waid, P. P.; Sabol,
J. S.; McCarthy, J. R. Tetrahedron Lett. 1994, 35, 5177.
(6) (a) Chen, C.; Wilcoxen, K.; Kim, K.-i.; McCarthy, J. R. Tetrahedron
Lett. 1997, 38, 7677. (b) Chen, C.; Wilcoxen, K.; Zhu, Y.-F.; Kim, K.-i.;
McCarthy, J. R. J. Org. Chem. 1999, 64, 3476.
(7) (a) Xue, L.; Lu, L.; Pederson, S. D.; Liu, Q.; Narske, R. M.; Burton,
D. J. J. Org. Chem. 1997, 62, 1064. (b) Lu, L.; Burton, D. J. Tetrahedron
Lett. 1997, 38, 7673.
1
Compounds in Medicinal Chemistry and Biomedical Applications; Filler,
R., Kobayashi, Y., Yagupolski, L. M., Eds.; Elsevier Science Publishers
B. V.: Amsterdam, 1993. (e) Organofluorine Chemistry, Principles and
Chemical Applications; Banks, R. E., Smart, B. E., Tatlow, J. C., Eds.;
Plenum Press: New York, 1994. (f) InVentory of Industrial Fluorobio-
chemicals; Becker, A., Ed.; Eyrolles: Pairs, 1996. (g) Smart, B. E. Chem.
ReV. 1996, 96, 1555. (h) Resnatic, G.; Soloshnok, V. A. Tetrahedron 1996,
5
2, 1. (i) Hudlicky, M., Pavlath, A. E., Eds. Chemistry of Organic Fluorine
Compounds; American Chemical Society: Washington, DC, 1996; #187.
2) (a) Burton, D. J.; Yang, Z.-Y.; Morken, D. A. Tetrahedron 1994,
0, 2993. (b) Burton, D. J.; Yang, Z.-Y. Tetrahedron 1992, 48, 189.
(
5
1
0.1021/ol0200697 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/22/2002

8
1
-trifluoromethylvinylstannanes also has been reported.
ranged from 7 to 13 Hz, while for those cis with respect to
4
However, to the best of our knowledge, the synthesis of
polyfluorinated organotin reagent has not been reported
previously. We now wish to report the synthesis of poly-
fluorinated organotin reagents, (Z)-R-fluoro-â-trifluoro-
methylvinylstannanes, which we expect to be useful reagents
in the synthesis of fluorine-containing biologically active
compounds.
the F group, the JFFcis ranged from 21 to 31 Hz. In our cases,
4
JFF is equal to 12 Hz; hence the configuration of the products
4 could be ascertained as the Z-isomer.
The stereochemical results may be rationalized as follows.
The mechanism for the formation of trifluoromethylated
R-fluoro-R,â-unsaturated sulfones is analogous to that of the
11
intramolecular Horner-Wadsworth-Emmons reaction and
The reaction sequences are shown in Scheme 1. Treatment
of diethyl (1-fluoro-1-phenylsulfonyl)methylphosphonate 1
is shown in Scheme 2. The reaction is initiated by the
9a
Scheme 2
Scheme 1
with n-butyllithium in tetrahydrofuran (THF) at -78 °C gave
carbanion 2 which was reacted with trifluoroacetic anhydride
to form the trifluoromethylated phosphonate 3. Without
isolation, 3 was attacked by Grignard reagents followed by
elimination of phosphonic acid anion to afford the desired
product 4 in 77-98% yields (three steps). The results are
summarized in Table 1. The reaction was stereospecific and
the Z-isomer was obtained exclusively.
nucleophilic attack of Grignard reagent on the carbon-
oxygen double bond of the carbonyl group, and for the
addition containing an asymmetric R-carbon, the Felkin-
Anh model of asymmetric induction predicts the predomi-
nant diastereomer. The incoming nucleophile preferentially
attacks the less hindered side of the plane containing the
12
Table 1. (Z)-R-Fluoro-â-trifluoromethylvinyl Sulfones 4
Prepared
CdO bond. Therefore, the relative steric bulk of F and SO
Ph play an important role in the stereoselectivity. The relative
steric bulk of F is smaller than that of SO Ph, and the attack
2
-
compd10
yield (%)a
Z:Eb
R
2
4
4
4
4
4
4
4
4
a
b
c
d
e
f
4-FC6H4
73
75
83
66
58
72
64
78
100:0
100:0
100:0
100:0
100:0
100:0
100:0
0:100c
is from the rear (the side of plane containing the small group)
of 3 forming the intermediate 5a, while the reverse is true
for the attack from the front, forming intermediate 5b. Each
of these intermediates decomposes via a syn elimination,
giving 4-Z or 4-E. In our case, formation of 5a will be
favored over 5b and the Z-isomer was obtained exclusively.
The polyfluorinated sulfones 4 could be easily converted
to polyfluorinated stannanes 6 by treatment of 4 with
4-ClC6H4
2-CH3C6H4
3-CH3C6H4
4-CH3C6H4
2-CH3OC6H4
C6H5
g
h
2-thienyl
a
Isolated yields. b The ratio of E- and Z-isomers is estimated on the basis
c
of NMR spectra and TLC data. According to the sequence rules, in 4h
(
sulfur containing compound), when the trifluoromethyl group is trans with
(
10) General procedure for the preparation of 4: n-Butyllithium (1
respect to the F group, the stereoisomer is assigned as the E-isomer, while
in other cases they are assigned as the Z-isomer.
mmol in 0.62 mL of hexane) was added dropwise over 10 min to a stirred
9
a
solution of diethyl (1-fluoro-1-phenylsulfonyl)methylphosphonate 1 (310
mg, 1 mmol) in absolute THF (15 mL) at -78 °C under nitrogen. The
mixture was stirred at -78 °C for 0.5 h, and trifluoroacetic anhydride (0.14
mL, 1 mmol) was added to it in one portion. Stirring was continued at -78
3
On the basis of F-CF coupling constants across the
°
C for 1 h, and the reaction mixture was allowed to warm to 25 °C. After
9b
double bond reported in the literature, if the trifluoromethyl
group was trans with respect to the F group, the JFFtrans
which the Grignard reagent (1.25 mmol) was added to the mixture which
was stirred for another 0.5 h. The reaction mixture was poured into dilute
HCl (2 M, 20 mL), and the water layer was extracted with ethyl ether (3 ×
4
2
0 mL). The combined organic layer was washed with water (3 × 10 mL)
(
8) Jeong, I. H.; Park, Y. S.; Kim, B. T. Tetrahedron Lett. 2000, 41,
917.
9) (a) Diethyl (1-fluoro-1-phenylsulfonyl)methylphosphonate 1 was
until neutral and dried over Na2SO4. Evaporation of the solvent gave a
residue, which was purified by column chromatography eluting with
petroleum ether (60-90 °C)-ethyl acetate (95:5) to give the product 4.
(11) Tasi, H.-J.; Thenappan, A.; Burton, D. J. J. Org. Chem. 1994, 59,
7085.
8
(
prepared according to the known method (McCarthy, J. R.; Matthews, D.
P.; Paolini, J. P. Org. Synth. 1995, 72, 216). (b) Burton, D. J.; Krutzsch, H.
C. J. Org. Chem. 1970, 35, 2125.
(12) Lodge, E. P.; Heathcock, C. H. J. Am. Chem. Soc. 1987, 109, 3353.
2084
Org. Lett., Vol. 4, No. 12, 2002

5
a
tributyltin hydride (2.0 equiv) and 2,2′-azobisisobutyronitrile
(
the Z-isomer. It has been reported that (fluorovinyl)sulfones
obtained from ketones were transformed to (fluorovinyl)-
stannanes with retention of configuration, while those
obtained from aldehydes gave mixtures of [(E)- and (Z)-
fluorovinyl]stannanes. In our studies, the retention of con-
figuration was observed for the hemolytic cleavage of the
vinyl phenylsulfonyl group with replacement by tributyltin.
The stereochemical results of stannylation may be rational-
ized by a radical addition-elimination mechanism.5
AIBN, 15 mol %) in high yields13 (Scheme 3). The results
Scheme 3
a,13
In summary, we have developed a new and convenient
methodology for the synthesis of (Z)-R-fluoro-â-trifluorom-
ethylvinylstannanes, which would be useful organotin poly-
fluorinated reagents for the synthesis of fluorine-containing
biologically active compounds. The detailed application of
this reagent in organic synthesis is being pursued.
are summarized in Table 2. This transformation was ste-
reospecific and the Z-isomer was obtained exclusively. No
Table 2. (Z)-R-Fluoro-â-trifluoromethylvinylstannanes 6
Prepared
Acknowledgment. Thanks are due to the National Natural
Science Foundation of China and Academia Sinica for
financial support.
compd14
R
yield (%)a
Z:E
6
6
6
6
6
6
6
6
a
b
c
d
e
f
4-FC6H4
98
83
93
93
98
79
77
98
100:0
100:0
100:0
100:0
100:0
100:0
4-ClC6H4
2-CH3C6H4
3-CH3C6H4
4-CH3C6H4
2-CH3OC6H4
C6H5
Supporting Information Available: Spectral data for
new compounds 4a-h and 6a-h. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL0200697
g
h
100:0
0:100c
(13) Khrimian, A. P.; Demilo, A. B.; Waters, R. M.; Liquido, N. J.;
Nicholson, J. M. J. Org. Chem. 1994, 59, 8034.
2-thienyl
(
14) General procedure for the preparation of 6: Tributyltin hydride
(
(
0.54 mL, 2 mmol) was added to a mixture of sulfone 4 (1 mmol), AIBN
25 mg), and toluene (5 mL). The reaction mixture was heated at 85 °C for
E-isomer was detectable from the NMR spectra and TLC
data. Similarly, the configuration of the products 6 was
ascertained on the basis of their coupling constants ( JFF) as
4
-6 h until completion of the reaction (by TLC). Evaporation of the toluene
gave a residue, which was purified by column chromatography, eluting with
petroleum ether (60-90 °C) to give the product 6.
4
Org. Lett., Vol. 4, No. 12, 2002
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