Stereoselective Preparation of (E)-(1,2-Difluoro-1,2-ethenediyl) Bis[tributylstannane] and Stereospecific Synthesis of (E)-1,2-Difluorostilbenes

Article abstract of DOI:10.1021/ol025686+

(matrix presented) The novel bisstannane (E)-(1,2-difluoro-1,2-ethenediyl) bis[tributylstannane] 2 was stereoselectively prepared in a high overall yield through a sequential synthetic route from chlorotrifluoroethylene 1. The synthetic application of this novel bisstannane 2 was exemplified in the Pd(PPh₃)₄/Cul-catalyzed cross-coupling reactions with aryl iodides, yielding (E)-1,2-diflourostilbenes 3 in moderate to high yields.

Full text of DOI:10.1021/ol025686+

ORGANIC
LETTERS
2002
Vol. 4, No. 9
1483-1485
Stereoselective Preparation of
(E)-(1,2-Difluoro-1,2-ethenediyl)
Bis[tributylstannane] and Stereospecific
Synthesis of (E)-1,2-Difluorostilbenes
Qibo Liu and Donald J. Burton*
Department of Chemistry, The UniVersity of Iowa, Iowa City, Iowa 52242
donald-burton@uiowa.edu
Received February 7, 2002
ABSTRACT
The novel bisstannane (E)-(1,2-difluoro-1,2-ethenediyl) bis[tributylstannane] 2 was stereoselectively prepared in a high overall yield through a
sequential synthetic route from chlorotrifluoroethylene 1. The synthetic application of this novel bisstannane 2 was exemplified in the
Pd(PPh3)4/CuI-catalyzed cross-coupling reactions with aryl iodides, yielding (E)-1,2-difluorostilbenes 3 in moderate to high yields.
The symmetrical (E)-1,2-difluoroethylene synthon is a
fundamental building block in numerous organic compounds.
Some aromatic derivatives have been found to possess liquid
crystal properties and are usable in LC electrooptical
devices.1,2 Other classes of compounds containing the (E)-
1,2-difluoro-1,2-ethenediyl unit have been rarely studied,
mainly because of the lack of efficient and stereoselective
synthetic methods for these materials.3 On the other hand,
the (E)-1,2-difluoro-1,2-ethenediyl organometallics have
never been reported. The only practical method for the
preparation of (E)-1,2-difluoro-stilbenes 3 is the addition-
elimination reaction between tetrafluoroethylene (TFE) and
aryllithium reagents.2,4,5 An alternative reaction using R,R-
bromofluorotoluene to form the disubstituted stilbene was
also reported, but with low yield and essentially no stereo-
selectivity.6 In general, the addition-elimination reaction has
been successfully applied to prepare a number of symmetrical
(E)-1,2-difluorostilbenes 3. However, because of the reaction
of aryllithium reagents with many functional groups, its scope
of application is limited. Furthermore, both the explosive
nature of TFE and the requirement of low-temperature
reaction conditions deter the industrial application of this
method.
In our research group, one of the approaches utilized for
the incorporation of fluorinated synthons is via fluorinated
organometallic reagents.7 This previously reported methodol-
ogy using organozinc or cadmium synthons stereospecifically
permitted monofunctionalization of the organometallic in-
termediate. To successfully achieve bis-functionalization
processes in one step, we have attempted to develop a stable
1,2-difluoro-bisorgano-metallic reagent. The requirements
that we demanded of such a reagent are that (1) it could be
prepared from a commercially available reagent; (2) it could
be prepared stereospecifically or stereoselectively; (3) it
(7) For selected papers for the synthesis and synthetic applications of
fluorinated organometallic reagents, see: (a) Burton, D. J.; Yang, Z.;
Morken, P. A. Tetrahedron 1994, 50, 2993. (b) Burton, D. J. In Synthetic
Fluorine Chemistry; Olah, G. A., Chambers, R. D., Prakash, G. K. S., Eds.;
Wiley: New York, 1992; pp 205-206. (c) Burton, D. J.; Yang, Z. In
Chemistry of Organic Fluorine Compounds II; Hudlicky, M., Pavlath, A.
E., Eds.; Washington, DC; 1995; pp 670-728. (d) Burton, D. J.; Yang, Z.
Tetrahedron 1992, 48, 189. (e) Xue, L.; Lu, L.; Pedersen, S.; Liu, Q.;
Narske, R.; Burton, D. J., Tetrahedron Lett. 1996, 37, 1921. (f) Xue, L.;
Lu, L.; Pedersen, S.; Liu, Q.; Narske, R.; Burton, D. J. J. Org. Chem. 1997,
62, 1064. (g) Fontana, S. A.; Davis, C. R.; He, Y.; Burton, D. J. Tetrahedron
1996, 52, 37. (h) Davis, C. R.; Burton, D. J. Tetrahedron Lett. 1996, 37,
7237. (i) Davis, C. R.; Burton, D. J. J. Org. Chem. 1997, 62, 9217. (j) Liu,
Q.; Burton, D. J. Tetrahedron Lett. 2000, 41, 8045.
(1) Sato, K.; Inoue, S.; Machida, K. U.S. Patent 5,380,461 (Cl. 252-
299.61, Co9K19/34), 10 Jan 1995; JP Appl. 90/96, 259, 13 Apr 1990; CA
122: P252298x.
(2) Inoue, S.; Asahi, M.; Honda, K. Rep. Asahi. Glass Found. 1995, 37.
(3) Jing, N.; Lemal, D. M. J. Org. Chem. 1994, 59, 1844.
(4) McGrath, T. F.; Levine, R. J. Am. Chem. Soc. 1955, 77, 4168.
(5) Dixon, S. J. Org. Chem. 1956, 21, 400.
(6) Kam, T.; Lim, T. J. Chem. Soc., Perkin Trans. 2 1993, 147.
10.1021/ol025686+ CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/29/2002

would be stable at room temperature or above; and (4) it
could be readily functionalized. A reagent that met these
requirements could be utilized by any workers (not just
specialists) and could be readily adopted to scale-up.
Scheme 2
The stereoselective synthesis of (E)-(1,2-difluoro-1,2-
ethenediyl) bis[tributylstannane] 2 is described in Scheme
1. Chlorotrifluoroethylene 1 was treated with an n-butyl-
Scheme 1
It was found that this organometallic reagent may be stored
at room temperature indefinitely without decomposition.
To evaluate the potential of 2 for bis-functionalization,
we attempted the coupling of 2 with aryl iodides. As
summarized in Table 1, (E)-1,2-difluorostilbenes 3 may be
Table 1. Preparation of (E)-1,2-Diflurostilbenes
lithium/hexanes solution and quenched in situ with chloro-
trimethylsilane to give the trifluorovinyltrimethylsilane 4 as
a crude product. The crude 4 in THF and hexanes was
reduced to an isomeric mixture of 91:9 of Z/E 5 with LiAlH4.
isolated
yielda (%)
Both the isomeric ratio and yields were determined from 19
F
entry
Arl
conditions
NMR integration using PhCF3 as an internal standard. We
could not separate completely either 4 or 5 from the solvents
since their boiling points are too close to those of the
solvents. However, these solvents never caused any problems
in subsequent reactions. On the contrary, the simplified
procedures led to higher efficiency and were much more
convenient. When 5 was reacted in THF with Bu3SnOSnBu3
in the presence of catalytic amount of tetrabutylammonium
fluoride, a 93:7 Z/E mixture of difluorostannanes 6 was
isolated in nearly quantitative yield.7f The isomeric ratio of
6 was enhanced from 93:7 Z/E to 97:3 after chromatographic
separation. It is worth mentioning that the chromatographic
separation of the two isomers is not required, because as
illustrated in Scheme 2 the (E)-isomer 6E decomposes during
the metalation step with n-BuLi, presumably as a result of a
LiF anti elimination. The 1,2-difluoroethenyltributylstannanes
(6Z:6E ) 97:3) were treated with a bulky base, lithium
2,2,6,6-tetramethylpiperidide to form the corresponding
vinyllithium reagent 7Z. Subsequent trapping of the lithium
intermediate 7Z with tributyltin chloride yields the bis-
stannane 2 in 100% isomeric purity and nearly quantitative
isolated yield. The bis-stannane 2 is a stable, colorless liquid.
1
2
3
4
5
6
7
8
C6H4I
rt/2 h
rt/2 h
86
85
83
89
70
63
62
51
m-CF3C6H4I
p-EtOOCC6H4I
p-CH3C6H4I
p-MeOC6H4I
o-ClC6H4I
rt/0.5 h
rt/2 h
60 °C/8 h
rt/20 h
rt/20 h
rt/24 h
o-BrC6H4I
o-MeOC6H4I
a The isolation process consists of flash chromatography and crystal-
lization of the (E)-1,2-difluorostilbenes from the by-product, Bu3Snl. Further
recrystallization of the crude crystals from ethanol or ether gave the product
as fine crystals.
stereospecifically synthesized from the Pd(PPh3)4/CuI-
catalyzed cross-coupling reaction between the bis-stannane
2 and aryl iodides.8 The cross-coupling reaction is sluggish
(8) Typical Procedure for (E)-(1,2-Difluoro-1,2-ethenediyl) Bis[3′-
trifluoromethylbenzene], 3-(2). A one-neck 10-mL round-bottom flask
equipped with a Teflon-coated stir bar and attached to a nitrogen tee was
charged with 0.64 g (1.0 mmol) of (E)-(1,2-difluoro-1,2-ethenediyl) bis-
[tributylstannane], 0.54 g (2.0 mmol) of 3-iodobenzotrifluoride, 1.5 mL of
THF, 1.5 mL of DMF, 0.19 g (1 mmol) of CuI, and 0.11 g (5 mol %) of
Pd(PPh3)4. The reaction mixture was stirred at room temperature. An
1484
Org. Lett., Vol. 4, No. 9, 2002

without the CuI cocatalyst and gives lower yields of stilbenes.
In the literature, the current preparative method employed
aryllithium reagents in an addition-elimination reaction at
low temperature to generate the corresponding (E)-1,2-
difluorostilbenes 3.2,4,5 In contrast to the current preparative
method via reaction of aryllithium reagents with TFE, our
bisstannane strategy has a wider scope of functional group
tolerance and is carried out under mild reaction conditions.
In summary, we have reported the first synthesis of (E)-
(1,2-difluoro-1,2-ethenediyl) bis[tributylstannane] 2 and its
synthetic application in the stereospecific preparation of (E)-
1,2-difluorostilbenes 3.9 We anticipate that this novel flu-
orinated organometallic reagent 2 will play an important role
in future synthetic organofluorine chemistry.10,11
exothermic reaction occurred, and the reaction mixture quickly turned to a
dark homogeneous solution. 19F NMR analysis was employed to monitor
the progress of the reaction. After the reaction mixture had been stirred for
2 h, the 19F NMR signal of the (E)-(1,2-difluoro-1,2-ethenediyl) bis-
[tributylstannane] had disappeared and two new singlets (-63 and -151
ppm) were observed. The dark reaction mixture was poured onto a silica
gel column and eluted with pentane, Rf ) 0.5. Removal of most of the
solvent via rotary evaporation yielded a liquid, which gave colorless crystals
after being stored at room temperature overnight. These crystals were further
purified via recrystallization from ethanol. Removal of the solvent at rt/1
mmHg yielded 0.29 g (85%) of colorless crystals, mp 55-56 °C. 19F NMR
Acknowledgment. We thank the National Science Foun-
dation for financial support of this work.
Supporting Information Available: Complete experi-
mental details for the synthesis outlined in Scheme 1 and
Table 1 and spectroscopic data. This material is available
free of charge via the Internet at http://pubs.acs.org.
1
δ -63.45 (s, 6 F), -151.32 (s, 2 F); H NMR δ 8.02 (s, 2 H), 7.93 (d, J
) 8 Hz, 2 H), 7.65 (d, J ) 8 Hz, 2 H), 7.58 (dd as t, J ) 8 Hz, 2 H);
{1H}13C NMR δ 148.13 (2nd order due to virtual coupling), 131.38 (q, J
) 33.0 Hz), 130.60 (t, J ) 9.3 Hz), 129.27 (s), 129.05 (tq, J ) 9.1, 1.1
Hz), 126.06 (q, J ) 3.6 Hz), 123.92 (q, J ) 272.3 Hz), 122.84 (tq, J ) 7.5,
4.0 Hz); FTIR (CCl4, cm-1) 3086.0 (vw), 1495.3 (w), 1442.7 (w), 1335.8
(s), 1311.6 (w), 1267.8 (w), 1250.0 (m), 1183.6 (m), 1173.1 (s), 1139.9
(s), 1079.4 (m); GC-MS (m/e) 352 (M+, 100), 333 (28), 282(27), 263 (29),
233 (44), 214 (88); UV (CHCl3) 259 nm (ꢀ ) 10800 cm-1 M-1), 314 nm
(ꢀ ) 12200 cm-1M-1); HRMS calcd for C16H8F8 352.0498, obsd 352.0511.
OL025686+
(9) Attempts to prepare unsymmetrical stilbenes via sequential coupling
of the bis-stannane were unsuccessful.
(10) In a preliminary experiment, 2 reacted with (E)-C6H5CHdCHBr
under similar conditions to stereospecifically give (1E,3E,5E)-3,4-difluoro-
1,6-diphenylhexatriene in 52% yield.11
(11) Liu, Q. The University of Iowa, unpublished work.
Org. Lett., Vol. 4, No. 9, 2002
1485