Cross-coupling reactions of alkenylsilanols with fluoroalkylsulfonates: Development and optimization of a mild and stereospecific coupling process

Article abstract of DOI:10.1016/j.tetlet.2010.11.133

The development of an effective protocol for the palladium-catalyzed cross-coupling of (E)-alkenylsilanols with aryl triflates is described. A critical component in the optimization of this method was balancing the stability and reactivity of the triflates in the presence of a nucleophilic promoter. This report highlights the use of a slightly soluble Br?nsted base promoter that allows for a low, steady-state concentration of alkenyl(dimethyl)silanolate in solution, thus facilitating cross-coupling in preference to S-O bond cleavage of the triflate.

Full text of DOI:10.1016/j.tetlet.2010.11.133

Tetrahedron Letters 52 (2011) 2165–2168
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Tetrahedron Letters
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Cross-coupling reactions of alkenylsilanols with fluoroalkylsulfonates:
development and optimization of a mild and stereospecific coupling process
⇑
Scott E. Denmark , Christopher S. Regens
245 Roger Adams Laboratory, PO Box 18, Department of Chemistry, University of Illinois, 600 S. Mathews Avenue, Urbana, IL 61801, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 3 December 2010
The development of an effective protocol for the palladium-catalyzed cross-coupling of (E)-alkenylsila-
nols with aryl triflates is described. A critical component in the optimization of this method was balanc-
ing the stability and reactivity of the triflates in the presence of a nucleophilic promoter. This report
highlights the use of a slightly soluble Brønsted base promoter that allows for a low, steady-state concen-
tration of alkenyl(dimethyl)silanolate in solution, thus facilitating cross-coupling in preference to S–O
bond cleavage of the triflate.
Dedicated Issue to Harry Wasserman
Ó 2010 Elsevier Ltd. All rights reserved.
Transition metal catalyzed cross-coupling reactions have revo-
lutionized the construction of carbon–carbon and carbon hetero-
atom bonds.1 The introduction of new organometallic donors and
organic electrophiles has led to expanded functional group com-
patibility and has reduced the formation of toxic by-products.2 Ini-
tial reports on cross-coupling reactions focused on the use of
highly active leaving groups such as iodides and diazonium ions.
However, in recent years, advances in cross-coupling of aryl bro-
mides and chlorides have been made possible by the development
of ligands that facilitate the oxidative addition of the organic halide
to a palladium(0) catalyst.3 By analogy to aliphatic substitution,
alcohols need to be activated as leaving groups. Thus, the introduc-
tion of triflates,4 and in recent years mesylates,5 tosylates,6 phos-
phonates,7 carbonates, and carboxylates,8 has enabled the use of
such ‘activated’ alcohols as cross-coupling electrophiles.
Triflates (R = CF3) and nonaflates (R = C4F9) are the most widely
employed class of pseudohalides in both the Kosugi–Migita–Stille9
and Suzuki–Miyaura10 cross-coupling reactions.11 Such electro-
philes are useful; they can allow conversion of aromatic or enolic
C–O bonds into carbon-carbon bonds by a simple two-step se-
quence (Scheme 1).12
In the past several years, reports from these laboratories have
demonstrated that a number of organosilanol reagents undergo
efficient cross-coupling with a variety of organohalides, under both
fluoride-promoted13 and Brønsted base promoted14 cross-coupling
conditions. The ability to access two different modes of activation,
the mild reaction conditions, the ease in preparation and stability
of these reagents, and the generation of benign by-products illus-
trate some of the advantages of organosilanol reagents. As in other
coupling processes, the scope of the electrophile is strongly influ-
enced by the choice in the palladium/ligand combination. For
example, bulky, electron-rich palladium complexes such as (t-
Bu3P)2Pd are critical for the cross-coupling of arylsilanolates with
aryl bromides15 whereas Buchwald type ligands allow for the
cross-coupling of alkenylsilanolates with aromatic chlorides.16
The cross-coupling of organosilanes with triflates finds prece-
dent in the work of Hiyama who found that alkenyl, alkynyl, aryl,
and alkyl mono-, di-, and trifluorosilanes can combine with a range
of alkenyl and aryl triflates.17 Moreover, a report from these labo-
ratories described the coupling of alkenylsilanols with aryl triflates
under activation by hydrated fluoride sources.18
The current study focuses on evaluating Brønsted base activa-
tion of alkenyl(dimethyl)silanols to expand the scope of the elec-
trophile to include the use of sulfonates. Because silanol-based
cross-coupling reactions involve a nucleophilic component, the
development of such a method is challenging given the sensitivity
of sulfonates toward basic and nucleophilic reagents.19 Therefore,
two major issues need to be addressed to develop a protocol for
a Brønsted base promoted cross-coupling reaction. First, the lower
reactivity of an aromatic triflate, relative to aromatic halides,
would require optimization of the palladium source and the ligand.
Second, the more challenging issue is to identify the reaction con-
ditions that would allow for Brønsted-base activation of the
organosilanol while avoiding unproductive S–O bond cleavage of
the aryl nonaflate or triflate (Scheme 2).
The startingpoint chosen was to survey a variety of Brønstedbase
activators for the reaction of phenyl nonaflate with hepte-
nyl(dimethyl)silanol (E)-1.20 Phenyl nonaflate was selected, rather
than the corresponding triflate, because arylnonaflates are more
reactive than the corresponding triflate in cross-coupling reactions
and they are less prone to hydrolytic or basic cleavage of the S–O
bond.21 The best starting point was to employ the palladium cata-
lyst, ligand, and solvent combination that was successful for the
fluoride-promoted cross-coupling of aryl triflates and nonaflates.22
Therefore, in the presence of PdBr2, 2-biphenyldi(t-butyl)phosphine
⇑
Corresponding author. Tel.: +1 217 333 0066; fax: +1 217 333 3984.
E-mail address: denmark@scs.uiuc.edu (S.E. Denmark).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.133

2166
S. E. Denmark, C. S. Regens / Tetrahedron Letters 52 (2011) 2165–2168
O
S
O
significant amount of 2-naphthol and low conversion to the de-
O
R
TG
OH
sired product (E)-3a (Table 1, entries 1–3). On the other hand, with
Na3PO4, K3PO4, or K3PO4ꢀH2O, low conversion to product was ob-
served, but more importantly S–O cleavage was completely sup-
pressed (Table 1, entries 4 and 5).
base
O
M
TG
cat
R
S
O
2
OR
O
Pd
The next phase of the study was to identify a suitable combina-
tion of palladium source and ligand. These initial studies showed
no significant differences between the palladium(II) sources and
the ligands employed (Table 2, entries 1–5). Interestingly, when
[(allyl)PdCl]2 was used in combination with X-Phos (Table 2, entry
3) fewer by-products were observed by GC analysis compared to
the combination with 2-dicyclohexylphosphino-20-60-dimethoxy-
biphenyl (S-Phos)3a (Table 2, entry 4). In the case where Pd(OAc)2
was employed the rate of cross-coupling was slightly faster than
with the halides (Table 2, entry 5); however, the reaction appeared
to stall after 6 h. Using Pd(dba)2 at room temperature (Table 2, en-
try 6) led to a slight increase in product yield (44%) compared to
palladium(II) salts. However, the reaction was still not complete
and silanol was eventually consumed to disiloxane. Although this
result was not optimal, it did demonstrate that a ‘ligandless’ palla-
dium(0) source was superior to palladium(II) sources. Accordingly,
reaction optimization continued with Pd(dba)2/X-Phos to increase
the overall conversion to product. Heating the reaction to 50 °C in-
creased the yield of (E)-3a to 57% along with 4% of 2-naphthol (Ta-
ble 2, entries 7 and 8). Finally, acceptable product conversion was
accomplished by heating the reaction mixture to 80 °C, giving 87%
of (E)-3a along with 5% of 2-naphthol.
To determine the actual concentration of K3PO4/silanolate in
solution at various temperatures, a series of titration experiments
were performed. The concentration of these components was
determined by mimicking the reaction conditions in Table 2 except
adding only K3PO4 to dioxane and stirring the mixture at room
temperature, 40 °C, 50 °C, 80 °C, and 100 °C. Aliquots were re-
moved and the concentration was determined by a total base titra-
tion. At 80 °C, the solution was approximately 0.07 M in K3PO4
(ꢁ12 mol % relative to triflate). This result suggests that at any gi-
ven time the solution is ca. 0.07 M in silanolate. Thus, a low, steady
state concentration of silanolate is maintained which is sufficient
to promote the cross-coupling instead of the cleavage of 2.
Although an acceptable yield of (E)-3a was achieved (by GC
analysis), additional studies were needed to identify the ideal
amounts of (E)-1, K3PO4, and ligand. Through extensive optimiza-
tion it was found that increasing the amount of silanol (E)-1 to
1.5 equiv, K3PO4 to 2.3 equiv and X-Phos to 0.052 equiv leads to
complete conversion of 2-naphthyl triflate. Preparatively, this
combination of reaction variables gave a 76% yield of 3a after 4 h
at 80 °C along with ꢁ3% of 2-naphthol.
O
O
R
S
O
R = CF3 or C4F9
M = Sn, B, Si
TG
O
R'
Me
R'
R'
Scheme 1. Cross-coupling via activated alcohols.
(BPTBP) in dioxane at room temperature
a
wide range of
fluoride-free activators were tested (KOSiMe3, KOt-Bu, KH, NaH,
NaOH, CsOH, NaOMe, etc.). Unfortunately, all of these activators
gave low conversion and product yield with a significant amount
of S–O cleavage. These results confirmed that S–O cleavage once
again would be a major challenge. Therefore, a full optimization of
reaction variables was required to identify a suitable activator that
would significantly enhance the cross-coupling rate relative to the
rate of S–O cleavage.
Because soluble Brønsted bases provided primarily the S–O
cleavage product rather than the desired cross-coupling product,
insoluble or sparingly soluble bases were investigated to decrease
the concentration of the Brønsted base promoter in solution, thus
suppressing the undesired S–O cleavage pathway (Table 1). For
these studies 2-naphthyl triflate 2 was chosen (because the poten-
tial side-products could be easily identified by GC analysis) along
with (E)-1 and 2-dicyclohexylphosphino-20,40,60-triisopropylbiphe-
nyl (X-Phos)23 in dioxane. Carbonate bases led to the formation of a
path b
R
path a
O
S
O
R'
Pd catalyzed
path a
FG
O
+
FG
FG
OH
Me
Si
Me
path b
R'
OH
non-catalyzed
(E)-1
R: CF3 (triflate) or C4F9 (nonaflate)
Scheme 2. Divergent pathways for cross-coupling versus S–O bond cleavage.
Table 1
Optimization of Brønsted base for the cross-coupling of 2 with (E)-1
With a functioning catalytic system established, a series of aryl
triflates possessing different electronic and steric properties was
investigated to evaluate the generality of this cross-coupling reac-
tion (Table 3). Overall, the reaction performed well with a series of
electron-rich and sterically hindered aryl triflates and gave good
yields exclusively as the E-isomer (Table 3, entries 1–7). It should
also be noted that 7% or less of the phenol was observed in all
cases. With electron-rich substrates, complete reaction was ob-
served within 4 h (Table 3, entries 1–4). With sterically demanding
substrates (Table 3, entries 5 and 6) the reaction proceeded
smoothly; even the hindered 2,6-disubstituted arene was coupled
to afford a 71% yield. Importantly the TBS protected benzyl alcohol
gave the desired cross-coupling product in 80% yield (Table 3, entry
8). However, electron-deficient arenes were problematic (Table 3,
entries 9 and 10). In these cases a significant amount of S–O cleav-
age was observed, giving rise to reduced yields. These unsatisfac-
tory results suggested that the cross-coupling conditions
required further optimization for application to electron poor
triflates.
PdBr2 (5.0 mol%)
n-C5H11
(E)-3a
X-Phos (10 mol%)
OTf
+
(E)-1
Base (2.0 equiv)
dioxane, rt, 24 h
+
OH
2
Entrya
Basea
Yieldb (%)
(E)-3a
2-Naphthol
1c
2c
3d
4d
5d
6d
Na3CO3
K3CO3
4
8
10
17
31
16
11
13
15
—
2
12
Cs2CO3
Na3PO4
K3PO4
K3PO4ꢀH2O
a
Mass balance is unreacted starting material or disiloxane.
Yields calculated by GC conversion relative to tetradecane as an internal
standard.
Reactions appear to have stalled after 4 h.
Reactions stalled after 12 h.
b
c
d

S. E. Denmark, C. S. Regens / Tetrahedron Letters 52 (2011) 2165–2168
2167
Table 2
Optimization of catalyst and ligand for the cross-coupling of 2 and (E)-124
catalyst (5.0 mol%)
ligand (X mol%)
n-C5H11
(E)-3a
OTf
+
(E)-1
K3PO4 (2.0 equiv)
+
dioxane, time, temp.
OH
1.0 equiv
1.0 equiv
2
Entry
Palladium source
Ligand
Temp (°C)
Time (h)
Yielda (%)
(E)-3a
2-Naphthol
1
2
3
4
5
6
7
8
PdBr2
PdBr2
BPTBP
rt
rt
rt
rt
rt
rt
50
80
24
24
24
24
24
24
12
4
24
31
32
30
31
44
57
87
1
2
7
X-Phos
X-Phos
S-Phos
X-Phos
X-Phos
X-Phos
X-Phos
[(allyl)PdCl]2
[(allyl)PdCl]2
Pd(OAc)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
9
15
12
4
5
a
Yields calculated by GC conversion relative to tetradecane as an internal standard.
CF3
Table 3
Scope in aryl triflate
4
TfO
Pd(dba)2 (5.0 mol%)
X-Phos (5.2 mol%)
((o-tol)3P)Pd (5.0 mol %)
Josi-Phos(5.0 mol %)
Me
CF3
TfO
+
C5H11
Me
Me
Me
Si
OH
Si
R
R
C5H11
R
K3PO4 (2.3 equiv)
dioxane, 80 ºC
OH
toluene, 50ºC
24 h, 48%
C5H11
Me
R = C5H11
(E)-3i
(E)-1
(E)-1
3
1.2 equiv
1.5 equiv
Pt-Bu2
Entrya
Aryl-OTf
Time (h)
Product
Yieldb (%)
PCy2
Fe
76d
72c
71c
78c
77c
71c
72c
80c
30c
11c
Josi-Phos
1
2
3
4
5
6
7
8
9
2-Naphthyl
C6H5
4
4
4
4
4
4
4
4
2
2
3a
3b
3c
3d
3e
3f
3g
3h
3i
4-MeO(C6H4)
4-Me(C6H4)
2-Me(C6H4)
2-MeO(C6H4)
2,6-Me(C6H3)
4-CH2OTBS(C6H4)
4-CF3(C6H4)
4-NO2(C6H4)
Scheme 3. Cross-coupling of an electron-deficient aryl triflate.
a sparingly soluble base (K3PO4) in dioxane allowed for a low-
steady state concentration of the active silanolate in solution. This
was found to suppress the S–O bond cleavage. At this concentra-
tion high yield and stereospecificity were obtained for the cross-
coupling of (E)-1 with a range of electron-rich and sterically
demanding aryl triflates.
10
3j
a
b
c
Reactions employed 1.5 equiv of silanol.
Crude product contained below 7% of the corresponding aryl alcohol.
Yield of chromatographed, distilled products.
Yield of analytically pure material.
d
Acknowledgments
To improve the generality of the Brønsted base promoted cross-
We are grateful to the National Institutes of Health for generous
financial support (GM63167). C.S.R. thanks Eli Lilly Research Labo-
ratories and Johnson & Johnson PRI for graduate fellowships.
coupling of aryl triflates with (E)-1, the nucleophilicity of the silan-
olate was attenuated by the preparation of a variety of metal salts
M+(E)-1ꢂ with the expectation that S–O bond cleavage would be
attenuated (M = Li, MgBr, Cu, Ag). These silanolate salts were easily
prepared by irreversible deprotonation of (E)-1. A solution of the
corresponding salt could then be evaluated in the cross-coupling
reaction with 4-(trifluoromethyl)phenyl triflate 4. Unfortunately,
the use of these salts did not significantly improve the cross-
coupling reaction. Either the reaction stalled at low conversion or
was plagued by disiloxane formation or S–O cleavage.
References and notes
1. (a)Metal-Catalyzed Cross-Coupling Reactions; de Meijere, A., Diederich, F., Eds.,
2nd ed.; Wiley-VCH: Weinheim, 2004; (b) Hegedus, L. S. Transition Metals in the
Synthesis of Complex Organic Molecules, 2nd ed.; University Science Books:
Sausalito, 1999; (c)Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E., Ed.; Wiley Interscience: New York, 2002; (d)Cross-
Coupling Reactions:
A Practical Guide; Miyaura, N., Ed. Topics in Current
These results warranted another round of optimization of all
reaction variables, using 4 as the acceptor. Through extensive eval-
uation of solvent, additives, palladium pre-catalysts, ligands, and
bases, the best result was obtained using a combination of K3PO4,
((o-tol)3P)2Pd and (Josi-Phos)6f in toluene at 50 °C. Under these
conditions a 48% yield (GC) of the desired cross-coupling product
was obtained with approximately 20% S–O cleavage (Scheme 3).
In conclusion, the work presented here demonstrates that alke-
nyl silanols are capable of undergoing mild and smooth palladium-
catalyzed cross-coupling with aryl triflates under Brønsted base
activation. Key to the success of this method was the discovery that
Chemistry; Springer: Berlin, 2002; Vol. 219,.
2. (a) Negishi, E.; Liu, F. In Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.,
Stang, P., Eds.; Wiley, 1998; pp 1–11; (b) Negishi, E. J. Organomet. Chem. 2002,
653, 34–40.
3. (a) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 9722–
9723; (b) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411–2413; (c)
Wolfe, J. P.; Singer, R. A.; Yang, B. H.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121,
9550–9561; (d) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020–
4028; (e) Navarro, O.; Kelly, R. A., III; Nolan, S. P. J. Am. Chem. Soc. 2003, 125,
16194–16195; For a recent review on the development of ligands for the cross-
coupling of aryl chlorides, see: (f) Bedford, R. B.; Cazin, C. S. J.; Holder, D. Coord.
Chem. Rev. 2004, 248, 2283–2321.
4. For organotin coupling to triflates, see: (a) Echavarren, A. M.; Stille, J. K. J. Am.
Chem. Soc. 1987, 109, 5478–5486; (b) Scott, W. J.; Stille, J. K. J. Am. Chem. Soc.

2168
S. E. Denmark, C. S. Regens / Tetrahedron Letters 52 (2011) 2165–2168
1986, 108, 3033–3040; (c) Kwon, H. B.; McKee, B. H.; Stille, J. K. J. Org. Chem.
1990, 55, 3114–3118; For organoboron coupling to triflates, see: (d) Oh-e, T.;
Miyaura, N.; Suzuki, A. J. Org. Chem. 1993, 58, 2201–2208.
10. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483; (b) Suzuki, A. In
Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-
VCH: Weinheim, 1998. Chapter 2; (c) Suzuki, A. J. Organomet. Chem. 1999, 576,
147–168.
11. (a) Negishi, E. In Handbook of Organopalladium Chemistry for Organic Synthesis;
John Wiley and Sons: New York, 2002; Vol. 1,; (b) Fugami, K; Kosugi, M. Top.
Curr. Chem. 2002, 219, 87–130. and references cited therein; (c) Miyaura, N.
Top. Curr. Chem. 2002, 219, 11–59. and references cited therein; (d) Hassan, J.;
Sevigonon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359–
1469; (e) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58, 9633–9695.
12. For the reviews on the synthesis of organo-triflates and nonaflates, see: (a)
Stang, P. J.; Hanack, M.; Subrmanian, L. R. Synthesis 1982, 85–126; (b) Ritter, K.
Synthesis 1993, 735–762.
13. For reviews, see: (a) Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835–
846; (b) Denmark, S. E.; Sweis, R. F. Chem. Pharm. Bull. 2002, 50, 1531–1541; (c)
Denmark, S. E.; Ober, M. H. Aldrichim. Acta 2003, 36, 75–85; (d) Denmark, S. E.;
Sweis, R. F. In Metal Catalyzed Cross-Coupling Reactions; de Meijere, A., Ed.;
Wiley-VCH: Weinheim, 2004. Chapter 4.
14. (a) Denmark, S. E.; Baird, J. D. Chem. Eur. J. 2006, 12, 4954–4963; (b) Denmark,
S. E.; Regens, C. S. Acc. Chem. Res. 2008, 41, 1486–1499.
15. Denmark, S. E.; Smith, R. C.; Chang, T. W.-T.; Muhuhi, J. M. J. Am. Chem. Soc.
2009, 131, 3104–3118.
16. (a) Denmark, S. E.; Kallemeyn, J. M. J. Am. Chem. Soc. 2006, 128, 15958–15959;
(b) Denmark, S. E.; Baird, J. D. Tetrahedron 2009, 65, 3120–3129.
17. Hatanaka, Y.; Hiyama, T. Tetrahedron Lett. 1990, 31, 2719–2722.
18. Denmark, S. E.; Sweis, R. F. Org. Lett. 2002, 4, 3771–3774.
19. Neuville, L.; Bigot, A.; Dau, M. E. T. H.; Zhu, J. J. Org. Chem. 1999, 64, 7638–7642.
20. Heptenyldimethylsilanol (E)-1 was prepared according to known methods:
Denmark, S. E.; Wehrli, D. Org. Lett. 2000, 2, 565–568.
21. It has been reported that nonaflates are less susceptible than triflates to
nucleophilic attack at the sulfur atom. We propose that this is the source of the
undesired phenol formation. Riggleman, S.; DeShong, P. J. Org. Chem. 2003, 68,
8106–8109.
5. (a) Percec, V.; Bae, J.-Y.; Hill, D. H. J. Org. Chem. 1995, 60, 1060–1065; (b) Percec,
V.; Bae, J.-Y.; Zhao, M.; Hill, D. H. J. Org. Chem. 1995, 60, 176–185; (c) Percec, V.;
Bae, J.-Y.; Hill, D. H. J. Org. Chem. 1995, 60, 6895–6903; (d) Percec, V.; Golding,
G. M.; Smidrkal, J.; Weichold, O. J. Org. Chem. 2004, 69, 3447–3452; (e) Naber, J.
R.; Fors, B. R.; Wu, X.; Gunn, J. T.; Buchwald, S. L. Heterocycles 2010, 80, 1215–
1226; (f) Kuroda, J.; Inamota, K.; Hiroya, K.; Doi, T. Eur. J. Org. Chem. 2009,
2251–2261; (g) So, C. M.; Lau, C. P.; Kwong, F. Y. Angew. Chem., Int. Ed. 2008, 47,
8059–8063; (h) So, C. M.; Lee, H. W.; Lau, C. P.; Kwong, F. Y. Org. Lett. 2009, 11,
317–320; (i) Zhang, L.; Qing, J.; Yang, P.-Y.; Wu, J. Org. Lett. 2008, 10, 4971–
4974; (j) Kobayashi, Y.; Mizojiri, R. Tetrahedron Lett. 1996, 37, 8531–8534; (k)
Ueda, M.; Saitoh, A.; Oh-tani, S.; Miyuara, N. Tetrahedron 1998, 54, 13079–
13086.
6. (a) Steinhuebel, D.; Baxter, J. M.; Palucki, M.; Davies, I. W. J. Org. Chem. 2005, 70,
10124–10127; (b) Huffman, M.; Yasuda, N. Synlett 1999, 4, 471–473; (c) Fu, X.;
Zhang, S.; Yin, J.; McAllister, T. L.; Jiang, S. A.; Tann, C.; Thiruvengadam, T. K.;
Zhang, F. Tetrahedron Lett. 2002, 43, 573–576; (d) Wu, J.; Liao, Y.; Yang, Z. J. Org.
Chem. 2001, 66, 3642–3645; (e) Schio, L.; Chatreaux, F.; Klich, M. Tetrahedron
Lett. 2000, 41, 1543–1547; (f) Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2003,
125, 8704–8705; (R)-1-[(Sp)-2-(dicyclohexylphosphino)ferrocenyl]ethyldi-
tert-butylphosphine (Josi-Phos), (g) Klapars, A.; Campos, K. R.; Chen, C. Y.;
Volante, R. P. Org. Lett. 2005, 7, 1185–1188; (h) Zhang, L.; Meng, T.; Jie Wu, J. J.
Org. Chem. 2007, 72, 9346–9349; (i) Bhayana, B.; Fors, B. P.; Buchwald, S. L. Org.
Lett. 2009, 11, 3954–3957; (j) So, C. M.; Lau, C. P.; Chan, A. S. C.; Kwong, F. Y. J.
Org. Chem. 2008, 73, 7731–7734; (k) Wilson, D. A.; Wilson, C. J.; Rosen, B. M.;
Percec, V. Org. Lett. 2008, 10, 4879–4882; (l) Zhang, L.; Meng, T.; Wu, J. J. Org.
Chem. 2007, 72, 9346–9349; (m) Nguyen, H. N.; Huang, X.; Buchwald, S. L. J. Am.
Chem. Soc. 2003, 125, 11818–11819; (n) Brenstrum, T.; Gerristma, D. A.;
Adjabeng, G. M.; Frampton, C. S.; Britten, J.; Robertson, A. J.; McNulty, J.;
Capretta, A. J. Org. Chem. 2004, 69, 7635–7639.
7. (a) Hayashi, T.; Yoshio, K.; Okamoto, Y.; Kumada, M. Tetrahedron Lett. 1981, 22,
4449–4452; (b) Gauthier, D.; Beckendorf, S.; Gøgsig, T. M.; Lindhardt, A. T.;
Skrydstrup, T. J. Org. Chem. 2009, 74, 3536–3539; (c) Huffman, M. A.; Yasuda, N.
Synlett 1998, 471–473; (d) Nan, Y.; Yang, Z. Tetrahedron Lett. 1999, 40, 3321–
3324; (e) Lepifre, F.; Buon, C.; Rabot, R.; Bouyssou, P.; Coudert, G. Tetrahedron
Lett. 1999, 40, 6373–6376.
8. (a) Quasdorf, K. W.; Riener, M.; Petrova, K. V.; Garg, N. K. J. Am. Chem. Soc. 2009,
131, 17748–17749; (b) Quasdorf, K. W.; Tian, X.; Garg, N. K. J. Am. Chem. Soc.
2008, 130, 14422–14423; For reviews, see.; (c) Tobisu, M.; Chatani, N. Angew.
Chem., Int. Ed. 2009, 48, 3565–3568; (d) Goossen, L. J.; Goossen, K.; Stanciu, C.
Angew. Chem., Int. Ed. 2009, 48, 3569–3571; (e) Knochel, P.; Gavryushin, A.
Synfacts 2009, 200; Guan, B.-T.; Wang, Y.; Li, B.-J.; Yu, D.-G.; Shi, Z.-J. J. Am.
Chem. Soc. 2008, 130, 14468–14470.
22. See Ref. 12. It should also be noted that polar coordinating solvents such as THF,
diglyme, dioxane, and dimethoxyethane (DME) facilitated cross-coupling:
however, the best results were obtained using dioxane as the solvent.
23. X-Phos was chosen as the ligand because it has been reported to prevent
cyclometalation of palladium to the ligand especially in cationic palladium
complexes. For recent reviews on dialkylbiaryl phosphine ligands see: (a)
Martin, R.; Buchwald, S. L. Acc. Chem. Res. 2008, 41, 1461–1473; (b) Surry, D. S.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6338–6361.
24. Extensive optimization of all reaction variables was conducted ligands (NHC,
bidentate, monodendate, etc.), palladium precatalysts, additives and solvents.
It was found from these studies that Buchwald type dialkylbiaryl phosphine
ligands were optimal in ethereal solvents (THF, dioxane, and DME); while all
other combinations surveyed did not significantly improve the product yield. It
should also be noted that the major side products observed in these reactions
were disiloxane formation, from dimerization of (E)-1, and/or S–O bond
cleavage.
9. (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508–523; (b) Farina, V.;
Krishnamurthy, V.; Scott, W. J. Org. React. 1998, 50, 1–652; (c) Mitchell, T. N. In
Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-
VCH: Weinheim, 1998. Chapter 4.