Effects of Silicon Substituents on Cross-Coupling Reactions
SCHEME 10
room temperature. The solution was quenched with water (20 mL)
and extracted with EtOAc (5 × 20 mL), and the combined organic
phases were washed with brine (20 mL). The organic layer was
dried with MgSO4 (anhydrous) and filtered. The solvent was then
evaporated in vacuo to give a solid which was purified by column
chromatography (silica gel, CH2Cl2/hexane, 2/1) to afford 262 mg
The results of varying the silanolate stoichiometry in Table
5 provide strong support for this interpretation. The enhanced
efficiency of coupling of 6 compared to 1 with only 1.0 equiv
of TMSOK likely represents the higher equilibrium concentra-
tion of K+6- given the greater acidity of 6.34b However, this
advantage disappears in the intrinsic nucleophilicities of K+1-
and K+6- become important with superstoichiometric amounts
of TMSOK wherein the silanols are more fully deprotonated.
1
(79%) of 23 as yellow solid. Data for 23: mp 288 °C; H NMR
(500 MHz, CDCl3) 7.65 (d, J ) 8.4, 4 H, HC(4)), 7.60 (d, J ) 8.4,
4 H, HC(3)), 7.56 (s, 4 H, HC(9)), 7.21 (d, J ) 16.3, 2 H, HC(6)),
7.13 (d, J ) 16.3, 2 H, HC(7)); 13C NMR (126 MHz, CDCl3) 141.8
(C(5)), 136.8 (C(8)), 132.7 (C(3)), 131.9 (C(6)), 127.6 (C(4)), 127.4
(C(7)), 127.1 (C(9)), 119.2 (C(1)), 110.9 (C(2)); TLC Rf 0.26
(CH2Cl2/hexane, 2/1) [UV + KMnO4].
4-[2-[4-[2-(2-Methylphenyl)ethenyl]phenyl]ethenyl]-
benzonitrile (24). A solution of bis-silane 22 (390 mg, 1.0 mmol),
4-iodobenzonitrile (229 mg, 1.0 mmol, 1.0 equiv), and (allylPdCl)2
(9.3 mg, 0.025 mmol, 0.025 equiv) in DME (4 mL) was stirred at
room temperature for 5 min, and then TMSOK (512 mg, 4.0 mmol,
4.0 equiv) was added. The reaction mixture was stirred at room
temperature for 6 h, whereupon EtOAc (20 mL) was added and
the reaction was stirred for 10 min further. The reaction mixture
was then filtered through a short silica gel column (20 g), the plug
was washed with EtOAc (100 mL), and the solvent was evaporated
in vacuo. To the crude product were added 2-iodotoluene (128 µL,
1.0 mmol, 1.0 equiv), (allylPdCl)2 (9.3 mg. 0.025 mmol, 0.025),
and a solution of TBAF (3.0 mL, 1 M in THF, 3.0 mmol, 3.0 equiv).
The reaction mixture was stirred for 4 h at room temperature, and
then EtOAc (25 mL) was added. After being stirred 10 min further,
the reaction was quenched with water (25 mL) and extracted with
ethyl acetate (3 × 25 mL). The combined organic extracts were
washed with water (1 × 30 mL) and brine (1 × 30 mL). The organic
layer was dried over MgSO4 (anhydrous) and filtered. After
evaporation of the solvent, the residue was purified by column
chromatography (silica gel, hexane/CH2Cl2, 2/1) and sublimed to
afford 244 mg (76%) of 24 as a yellow solid. Data for 24: mp 294
°C (subl); 1H NMR (500 MHz, CDCl3) 7.64 (d, J ) 8.5, 2 H, HC-
(4)), 7.60 (m, 3 H, HC(3) and HC(15)), 7.54 (s, 4 H, HC(9) and
HC(10)), 7.38 (d, J ) 16.4, 1 H, HC(13)), 7.21 (m, 4 H, HC(6),
HC(16), HC(17), and HC(18)), 7.11 (d, J ) 16.3, 1 H, HC(7)),
7.01 (d, J ) 16.1, 1 H, HC(12)), 2.45 (s, 3 H, HC20)); 13C NMR
(126 MHz, CDCl3) 142.1 (C(5)), 138.3 (C(14)), 136.4 (C(8)), 136.1
(C(11)), 135.8 (C(19)), 132.7 (C(3)), 132.2 (C(6)), 130.7 (C(18)),
129.5 (C(17)), 127.9 (C(15)), 127.5 (C(4)), 127.3 (C(7)), 127.2
(C(9)), 127.0 (C(10)), 126.7 (C(16)), 126.5 (C(12)), 125.5 (C(13)),
119.3 (C(1)), 110.7 (C(2)), 20.1 (C(20)); IR (CHCl3) 3021 (m),
2227 (s), 1600 (s), 1514 (w), 1460 (w), 1214 (w), 1174 (w), 964
(s); MS (EI, 70 eV) 321 (M+, 100), 203 (13), 157 (16); TLC Rf
0.21 (hexane/CH2Cl2, 2/1) [UV + KMnO4]; GC tR 31.24 min
(100%) (HP5, injector 225 °C, column 275 °C, 15 psi); HRMS
calcd for C24H19N1 331.1518, found 321.1517.
Conclusion
Through systematic examination of the steric and the
electronic effects on the efficiencies of the cross-coupling
reaction, we have established a qualitative scale of reactivity
that was found to be highly dependent on the method of
activation. The integrated reactivity order for fluoride activation
is (Me)CF3CH2CH2SiOH g Me2SiOEt ≈ Me2SiOH g Ph2SiOH
g Et2SiOH > MeSi(OEt)2 > i-Pr2SiOH > Si(OEt)3 . t-Bu2-
SiOH following 7/9/1/6/3/10/4/11/5 ) 1.24/1.02/1.00/0.92/0.89/
0.78/0.65/0.27/0.025. The integrated order for silanoate activa-
tion is Ph2SiOH > (Me)CF3CH2CH2SiOH > MeSi(OEt)2 g
Me2SiOH ≈ Si(OEt)3 ≈ Me2SiOEt . i-Pr2 following 6/7/10/
1/11/9/4 ) 3.85/1.86/1.21/1.00/0.94/0.93/0.04. This study re-
veals that a dimethylsilanol and a diisopropylsilanol are
comparable precursors for alkenyl transfer under fluoride
activation where as a dimethylsilanol is a more efficient
precursor than a diisopropylsilanol for alkenyl transfer under
silanolate activation. Analysis of the reactivity trends provided
additional support into the operation of different mechanistic
pathways for the different modes of activation.
From a preparative point of view, barring incompatibilities
with fluoride ion, reactions with this activator tend to be faster
and less sensitive to structural and electronic features of the
reactants. However, recent advances that employ preformed
metal silanolates stoichiometrically18 have made the nonfluoride
coupling reactions the method of first choice.
Experimental Section
General Experimental Procedures. See the Supporting Infor-
mation.
(E,E)-4,4′-(1,4-Phenylenediethendiyl)bisbenzonitrile (23).28 Bis-
silane 22 (390 mg, 1.0 mmol), 4-iodobenzonitrile (458 mg, 2.0
mmol, 2.0 equiv), and (allylPdCl)2 (9.3 mg. 0.025 mmol, 0.025
equiv) were dissolved in a solution of TBAF (4.0 mL, 1.0 mmol,
1 M in THF, 4 equiv). The reaction mixture was stirred for 6 h at
Acknowledgment. We are grateful for the National Institutes
of Health for generous financial support (GM63167).
Supporting Information Available: Full experimental details
for the preparation and characterization of all substrates and
products. Determination of response factors and raw GC data for
all competition experiments is also provided. This material is
(34) (a) Perez, P. J. Phys. Chem. A 2001, 105, 6182-6186. (b) For a
review on the acidity of organosilicon compounds, see: Bassindale, A. R.;
Taylor, P. G. The Chemistry of Organic Silicon Compounds; Rappoport,
Z., Apeloig, Y., Eds.; Wiley-VCH: Weinheim, 1989; Vol. 1, Chapter 12,
p 809. (c) For a review on silanols see: Lickiss, P. AdV. Inorg. Chem.
1995, 42, 147-262.
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J. Org. Chem, Vol. 71, No. 22, 2006 8509