features fluorous Wittig methodology11,14 and fluorous
amines15 described earlier. Although six steps were required,
product purifications, often the most important consideration
in fluorous syntheses, were easy, and the overall yield was
good. Compound 1 showed a high CF3C6F11/toluene partition
coefficient (98.7:1.3, 24 °C) and reacted with Pd(OAc)2
(AcOH, 95 °C) to give the yellow dimeric palladacycle 2 in
87% yield (partition coefficients at 24 °C, 95.5:4.5, CF3C6F11/
toluene; 95.9:4.1, CF3C6F11/DMF). A crystallized sample
melted at 78-80 °C and was thermally stable to 225 °C
(DSC/TGA). When DMF or CF3C6H5 solutions of 2 were
kept at 140 °C (2 h) or 100 °C (16 h), no decomposition
was detected visually (e.g., black residues) or by NMR.
Reactions with LiX (X ) I, Cl) gave the corresponding
palladacycle halides 3 and 4, which were much less soluble
than 2.16
Scheme 1. Synthesis of Fluorous Schiff Base and
Palladacyclesa
We first sought to demonstrate that 2 was a viable catalyst
precursor. Accordingly, a solution of an aryl halide in freshly
distilled DMF (4-8 mL) was sequentially treated with an
alkene, Et3N, and a standard solution of 2 in CF3C6H5
(0.010-0.020 mL; 0.68-1.83 × 10-6 mol %), as sum-
marized in Table 1. The apparently homogeneous samples
Table 1. Heck Reactions under High Turnover Conditionsa
a Conditions: (a) Rf8CH2CH2PPh3+I-, K2CO3, p-dioxane/H2O,
95 ˚C; (b) i-PrMgCl, THF; (c) Rf8CH2CH2CHO; (d) (Ph3P)3RhCl,
H2 (75 psi), EtOH/CF3C6H5, 40 ˚C; (e) Dess-Martin periodinane,
CF3C6H5; (f) NH2CH2CH2CH2Rf8, SnCl2(H2O)2, toluene, reflux,
Dean-Stark; (g) Pd(OAc)2, AcOH, 95 ˚C; (h) LiX (X ) Cl, I),
CF3C6H5/MeOH.
X
R1
R2
2 (nmol) t (h) conv (%) yield (%)
TON
I
I
H
H
CO2Me
Ph
3.438
3.438
9.168
14
24
48
100
94
77
100b
88c
49b
1 461 000
1 286 000
266 000
Br Ac CO2Me
“pony tails” for effective immobilization in fluorous
solvents.4b,11 However, we recently showed that the markedly
temperature-dependent solubilities of many fluorous com-
pounds in organic solvents can also be exploited.12 Such
thermomorphic behavior allows homogeneous reaction con-
ditions at higher temperatures, with catalyst recovery via
liquid/solid phase separation at lower temperatures. Since
Heck reactions normally require elevated temperatures, we
thought they would provide ideal test cases for comparing
the new and classical procedures.
Our attention was drawn to a cyclopalladated Schiff base
Heck catalyst precursor reported by Milstein, with just one
arene per palladium.13 We prepared a similar fluorous Schiff
base containing three pony tails (1) from commercial
p-iodobenzaldehyde as shown in Scheme 1. This sequence
a Conditions: ArX (ca. 5.000 mmol), alkene (ca. 1.25 equiv), NEt3 (ca
2 equiv), DMF (4-8 mL), 140 °C. b trans only. c trans/cis, 6.7/1.
were reacted at 140 °C and then cooled. GC analyses showed
Heck coupling products in 49-100% yields, corresponding
to turnover numbers (TON) of 266,000 to 1,461,000. This
places 2 among the best high-turnover Heck catalyst precur-
sors.9
Similar reactions were conducted in which 2 was intro-
duced as a solid and at much higher loadings (0.5 mol %).
The initially insoluble 2 dissolved as the DMF was warmed.
Upon cooling, palladium complexes precipitated. In reactions
of phenyl iodide, NMR analyses showed palladacycle iodide
3 to be the dominant species.17 Other materials remained
(11) (a) Rocaboy, C.; Rutherford, D.; Bennett, B. L.; Gladysz, J. A. J.
Phys. Org. Chem. 2000, 13, 596. (b) Rocaboy, C.; Hampel, F.; Gladysz, J.
A. J. Org. Chem. 2002, 67, in press.
(12) Wende, M.; Meier, R.; Gladysz, J. A. J. Am. Chem. Soc. 2001, 123,
11490.
(14) Soo´s, T.; Bennett, B. L.; Rutherford, D.; Barthel-Rosa, L. P.;
Gladysz, J. A. Organometallics 2001, 20, 3079.
(15) Rocaboy, C.; Bauer, W.; Gladysz, J. A. Eur. J. Org. Chem. 2000,
2621.
(13) (a) Ohff, M.; Ohff, A.; Milstein, D. Chem. Commun. 1999, 357.
(b) Closely related catalyst precursors with additional phenyl rings:
Blackmond, D. G.; Rosner, T.; Pfaltz, A. Org. Proc. Res. DeV. 1999, 3,
275. (c) Additional catalyst precursors with nitrogen-donor palladacycles:
Beletskaya, I. P.; Kashin, A. N.; Karlstedt, N. B.; Mitin, A. V.; Cheprakov,
A. V.; Kazankov, G. M. J. Organomet. Chem. 2001, 622, 89.
(16) At room temperature, 2 was soluble in fluorinated solvents such as
CF3C6F11, C8F17Br, CF3C6F5, and CF3C6H5 but poorly soluble in common
organic solvents such as CH2Cl2, CHCl3, acetone, and THF. Complexes 3
and 4 were completely insoluble in organic solvents and poorly soluble in
the preceding fluorinated solvents. However, solubilities in CF3C6F5 were
much higher above 50 °C, allowing NMR spectra to be recorded.
1994
Org. Lett., Vol. 4, No. 12, 2002