R – Pd – X + R′ – M
(M = Si, etc.)
III.2.4 Overview of Other
Palladium-Catalyzed Cross-Coupling
Protocols
TAMEJIRO HIYAMA and EIJI SHIRAKAWA
'
A. INTRODUCTION
In this section is reviewed the cross-coupling reaction of organometallic compounds containing a main group metal such as Si, Ge, Cd, In, Hg, Pb, or Bi, not covered in Sects. III.2.1–III.2.3. The carbon–metal bond of these compounds, although less polarized than those of the organometallics covered in preceding sections, has sufficient but not immoderate nucleophilicity to react with palladium(II) complexes. This character leads to chemoselective cross-coupling reactions. Organosilicon compounds have a weakly polarized C— Si bond and thus often need activation by a Lewis base to couple with electrophiles. Organolead compounds having electron-withdrawing ligands sometimes act as an electrophile to react with nucleophilic organometallic compounds, giving crosscoupled products.
B. ORGANOSILICON COMPOUNDS[1]–[4]
B.i. Alkenylsilane
Neutral organosilanes (R — SiMe3) are weak nucleophiles among the organometallics described in this section and generally do not undergo a desilylative coupling reaction with aryl halides in the presence of a palladium catalyst except for the following examples. Hallberg and Westerlund[5] reported that although trimethyl(vinyl)silane could transmetalate with an arylpalladium(II) complex to afford coupled products, aryl-substituted alkenylsilanes formed through the Heck type reaction also accompanied (Scheme 1). On the other hand, Kikukawa and co-workers[6] – [8] found that the reaction of trimethyl( - or-styryl)silanes with arenediazonium tetrafluoroborates gave a regioisomeric mixture of coupling products. The catalytic cycle of the reaction is considered to involve carbopalladation toward the C—C double bond of an alkenylsilane by an arylpalladium intermediate followed by tetrafluoroborate-assisted elimination of the silyl group and palladium(0) (Scheme 2).
Handbook of Organopalladium Chemistry for Organic Synthesis, Edited by Ei-ichi Negishi ISBN 0-471-31506-0 © 2002 John Wiley & Sons, Inc.
285
286 |
III |
Pd-CATALYZED CROSS-COUPLING |
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2% Pd(OAc)2 |
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4% PPh3 |
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R Et3N (1.4 equiv) |
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R |
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R |
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SiMe3 + |
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DMF, 70−125 |
°C |
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Me3Si |
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R = H, OMe, NO2, Me |
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51−60% |
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5−25% |
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Scheme 1 |
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Ph |
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ArN2+BF4− |
Ph |
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Ph |
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Ph |
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Ar |
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5% Pd(dba)2 |
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+ |
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MeCN, 25 °C |
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Ar |
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Ar |
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SiMe3 |
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Ar = Ph |
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B |
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C |
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4-Me-C6H4 |
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from |
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4-Br-C6H4 |
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97−100% yield |
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4-NO2-C6H4 |
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ArN2+BF4− |
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B + |
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10% Pd(dba)2 |
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SiMe3 |
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MeCN, 25 °C |
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68−100% yield |
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Ph |
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ArN2+BF4− |
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B + |
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10% Pd(dba)2 |
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from |
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Me3Si |
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MeCN, 25 °C |
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96−100% yield |
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to |
>99 |
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<1 |
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Scheme 2
In 1982 Yoshida et al.[9] disclosed that an organofluorosilicate underwent desilylative coupling with iodobenzene in the presence of a palladium catalyst under rather drastic reaction conditions (Scheme 3). Although the nucleophilicity at the carbon atom having a silicate group is apparently enhanced, a mixture of regioisomers resulted.
From the standpoint of organic synthesis, the coupling through carbopalladation of a C—C double bond of alkenysilanes is not useful because the reactions afford a mixture of isomers and the substrate is limited to alkenylsilanes. Hatanaka and Hiyama[10] overcame these drawbacks by using fluoride salts to in situ activate organosilicon compounds. Thus, an alkenyl(trimethyl)silane coupled with an aryl or alkenyl halide in the presence of a palladium catalyst and (Et2N)3S (Me3SiF2) , abbreviated as TASF, with retention of the double bond geometry of both substrates (Scheme 4).[10] Upon activation by a fluoride ion, the nucleophilicity of alkenylsilanes becomes adequate to complete transmetallation. This cross-coupling reaction is tolerant of a wide variety of functional groups such as ester, ketone, aldehyde, and alcohol. Furthermore, mild reaction conditions
III.2.4 OVERVIEW OF OTHER Pd-CATALYZED CROSS-COUPLING PROTOCOLS |
287 |
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5% Pd(OAc)2 |
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10% PPh3 |
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+ I−Ph |
Et3N |
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K2 |
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135 °C, 20 h |
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SiF5 |
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Ph |
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51% |
8% |
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Scheme 3 |
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2.5% [PdCl(η3-C3H5)]2 |
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I−Ar |
TASF (1.3 equiv) |
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Ar |
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HMPA, 50 |
°C |
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SiMe3 |
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Ar = 1-Np
4-Me-C6H4 83–98% 4-NO2-C6H4
4-NH2-C6H4
4-MeCO-C6H4
4-I-C6H4
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SiMe3 |
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R = n-Hex |
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(CH2)8COOMe |
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(CH2)9OCOMe |
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(CH2)8CHO |
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C(=CH2)CH2CH2Ph |
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Ph |
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n-Hex |
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SiMe3 + |
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n-Hex |
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OEt |
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SiMe3 |
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2.5% [PdCl(η3-C3H5)]2 5% P(OPh)3
TASF (1.3 equiv)
THF, 50 °C |
R |
52–100%
100%
n-Hex
76%
n-Hex
78%
OEt
Ph 45%
Ph
Ph 32%
Scheme 4
288 |
III Pd-CATALYZED CROSS-COUPLING |
prevent degeneration and/or isomerization of products: thermally labile trienes do not isomerize before the completion of the reaction. n-Bu4N F (TBAF) is equally effective but in some cases inferior to TASF; CsF and KF are futile for diene synthesis.[11] Under similar conditions, alkynyland allyl(trimethyl)silane also reacted with alkenyl or allyl bromides (vide infra).
The following mechanism is suggested for the cross-coupling of alkenylsilanes. Nucleophilic attack of a fluoride ion to the silicon atom of alkenylsilanes should afford a pentacoordinated silicate, whose nucleophilicity of the silicon-substituted carbon and Lewis acidity of silicon are both enhanced to undergo transmetallation effectively through a four-centered transition state (Scheme 5). The importance of Lewis acidity on the silicon is evidenced by the fact that the pentafluorosilicates, which should have sufficient nucleophilicity but lack a coordination site on silicon, were not effective substrates for the cross-coupling reaction (Scheme 3, vide supra).
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F − |
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Ar−Pd−X |
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ArPd |
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SiFMe3 |
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Scheme 5
Trimethyl(vinyl)silanes having an aliphatic substituent on vinyl, however, failed to couple with an aryl iodide under similar conditions, probably because they could not afford pentacoordinated silicates efficiently owing to the electron-donating nature of the substituent. To assist the formation of the pentacoordinated intermediates, the methyl group on the silicon atom was replaced by fluorine.[12] The coupling reaction of (E)-1-fluoro(methyl)silyl-1-octene with 1-iodonaphthalene clearly suggested that introduction of one or two fluorine atom(s) on silicon was effective (Scheme 6). Inertness of (E)-1-trifluorosilyl-1-octene is attributed to the formation of an unreactive hexacoordinated silicate. These findings led to the successful coupling reaction of various alkenylsilanes with aryl and alkenyl iodides with complete retention of configuration of both the coupling partners (Scheme 7).
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n-Hex |
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2.5% [PdCl(η3-C3H5)]2 |
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TASF (1.0 equiv) |
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SiMe3-nFn |
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THF, 50 °C |
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n |
Time (h) Yield (%) |
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Scheme 6
III.2.4 |
OVERVIEW OF OTHER Pd-CATALYZED CROSS-COUPLING PROTOCOLS |
289 |
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or |
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or |
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n-Hex |
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SiMe2F [A] |
n-Bu |
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n-Oct |
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coupling |
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product |
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12−24 h |
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or
I
[A]2.5% [PdCl(η3-C3H5)]2, TASF (1.5 equiv), THF, 60 °C
[B]5% Pd(PPh3)4, TASF (1.5 equiv), THF, 60 °C
[C]2.5% [PdCl(η3-C3H5)]2, TBAF (1.5 equiv), THF, 60 °C
Scheme 7
The cross-coupling reaction of alkenyl(fluoro)silanes with aryl halides sometimes produces small amounts of cine-coupled products in addition to the desired ipso-coupled products.[13] The cine-coupling is often striking in the reaction with organotin compounds. The isomer ratio of products produced by the reaction of 1-fluoro(dimethyl)silyl-1- phenylethene with aryl iodides is found to depend on the electronic nature of the substituent on aryl iodides (Scheme 8). An electron-withdrawing group like trifluoromethyl and acetyl favors the formation of the ipso-coupled product. To explain the substituent effect, a mechanism is proposed for the transmetallation of alkenylsilanes with palladium(II) complexes and is depicted in Scheme 9. It is considered that an electron-donating substituent on Ar enhances the nucleophilicity of the aryl group to promote an intramolecular nucleophilic attack of Ar to the cationic -carbon (path b), leading to the cine-coupled product.
290 |
III Pd-CATALYZED CROSS-COUPLING |
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2.5% [PdCl(η3-C3H5)]2 |
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I−Ar |
TBAF (1.1 equiv) |
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+ |
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THF, 60 |
°C |
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FMe2Si |
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Ar |
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Ar = 4-CF3-C6H4 |
24 h |
72% |
93 |
: |
7 |
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4-MeCO-C6H4 |
20 h |
73% |
88 |
: |
12 |
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4-F-C6H4 |
4 h |
80% |
79 |
: |
21 |
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Ph |
4 h |
69% |
75 |
: |
25 |
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4-Me-C6H4 |
14 h |
84% |
59 |
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41 |
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4-EtO-C6H4 |
20 h |
63% |
60 |
: |
40 |
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Scheme 8 |
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Ph |
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FMe2Si− a |
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Ph |
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+ |
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a |
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FMe2Si− |
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F |
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Pd |
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Pd |
Ar |
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Pd |
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b |
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F |
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[Si]− |
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[Si]− |
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Ar |
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[Si]− |
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H |
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Ph |
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Pd |
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X |
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H |
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Scheme 9
B.ii. Arylsilane
The coupling reaction of arylsilanes with aryl iodides is also mediated by a palladium catalyst and a fluoride ion.[14],[15] Optimized reaction conditions are as follows: (i) two fluorine atoms on silicon are required; (ii) an ethyl or propyl group as a dummy alkyl ligand is preferred, because a methyl group competitively participates in the crosscoupling reaction; and (iii) TBAF, a highly effective fluoride ion source, can be replaced by inexpensive KF. Various unsymmetrical biaryls are synthesized under the conditions (Scheme 10).
Aryl(chloro)silanes, upon pretreatment with KF, smoothly undergo the Pd-catalyzed coupling with aryl bromides and iodides to give various biaryls. For this procedure, Pd(OAc)2 (0.5 mol %)/P(o-tol)3 (0.5 mol %) is convenient (Scheme 11).
Under an atomospheric pressure of carbon monoxide, aryland alkenylsilanes undergo a carbonylative coupling reaction with aryl and alkenyl halides.[16],[17] The optimized conditions for arylsilanes were use of N,N-dimethyl-2-imidazolidinone (DMI) as a solvent and KF as a fluoride ion source (Scheme 12), whereas alkenylsilanes preferred THF and TBAF (Scheme 13).
Recently, Shibata and co-workers[18] found that aryl(trimethoxy)silanes were also applicable to the Pd-catalyzed cross-coupling reaction with aryl bromides (Scheme 14). A similar procedure using phenyl-, vinyland allyl(trialkoxy)silanes was also reported by Mowery and DeShong.[19]
III.2.4 OVERVIEW OF OTHER Pd-CATALYZED CROSS-COUPLING PROTOCOLS |
291 |
5% [PdCl(η3-C3H5)]2
KF (3 equiv) −
Ar1−SiRF2 + I−Ar2 Ar1 Ar2 DMF, 70−100 °C, 6−49 h
45−94%
Ar1 = Ph
4-Me-C6H4
4-CF3-C6H4
3-MeO-C6H4
R = Et, Pr
Ar2 = 4-EtO-C6H4 2-MeO-C6H4 3-MeO-C6H4 3-HOCH2-C6H4 3-MeCOOCH2-C6H4 4-NC-C6H4 4-MeCOO-C6H4 4-MeCO-C6H4 4-MeOCO-C6H4
3-HCO-C6H4
1-Np
Scheme 10
|
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KF (5 equiv) |
|
0.5% Pd(OAc)2 |
||
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0.5% P(o-tol)3 |
|||
Ar1−SiEtCl2 |
+ Br−Ar2 |
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Ar1−Ar2 |
DMF, 60 °C, 3 h |
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120 °C, 18 h |
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41−99% |
Ar1 = Ph |
Ar2 = 4-NC-C6H4 |
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4-CH3-C6H4 |
4-CF3-C6H4 |
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4-n-Pent-C6H4 |
4-F-C6H4 |
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4-CH3O-C6H4 |
4-MeOCO-C6H4 |
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3-MeO-C6H4 |
4-MeCO-C6H4 |
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2-Me-C6H4 |
3-HCO-C6H4 |
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2-NO2-C6H4
2-NC-C6H4 etc...
Scheme 11
2.5% [PdCl(η3-C3H5)]2 CO (1 atm)
KF (1.5 equiv)
Ar1−SiR1F2 + I−R2
DMI, 100 °C, 5−25 h
Ar1 = Ph
3-MeO-C6H4
4-CF3-C6H4
4-Me-C6H4
2-thienyl
R1 = Et, n-Pr
R2 = 3-HCO-C6H4 1-Np
4-MeCO-C6H4
4-NC-C6H4
4-MeOCO-C6H4
3-quinolinyl (E)-1-octen-1-yl
Scheme 12
Ar1 R2
O
38−80%
292 |
III Pd-CATALYZED CROSS-COUPLING |
n-Hex
SiF3
R = 3-HCO-C6H4 3-MeO-C6H4 3-HOCH2-C6H4 (E)-2-phenylethen-1-yl
Scheme 13
n-Hex R
O
43−71%
Ar1−Si(OMe)3 |
TBAF (1.05 equiv) |
|
THF, r.t., 30 min |
||
|
Ar1 = 4-(4-n-Pr-cyclohexyl)-C6H4 4-(4-n-Pent-cyclohexyl)-C6H4 4-(4-Et-cyclohexyl)-C6H4 4-(4-MeOCH2-cyclohexyl)-C6H4
4-n-Pent-C6H4 4-MeO-C6H4 3,4-F2C6H3
Ar2−Br (1.2 equiv) 5% Pd(OAc)2
15% PPh3 −
Ar1 Ar2
toluene, 120 °C, 3–30 h
61−92%
Ar2 = 3,4-F2C6H3 4-MeO-C6H4 4-NO2-C6H4 4-NC-C6H4 4-EtOCO-C6H4 3-pyridyl
4-MeCO-C6H4
Scheme 14
Aryl chlorides that are usually unreactive in Pd-catalyzed cross-coupling reactions are applicable to the reaction with aryland alkenylchlorosilanes using a fluoride ion reagent and a catalytic amount of (i-Pr3P)2PdCl2, (Cy2PCH2CH2PCy2)PdCl2, or [PdCl( 3-C3H5)]2
(Scheme 15).[20]
MeO |
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SiEtCl2 |
[A] or [B] |
Cl |
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COMe |
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Cl |
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Me |
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SiEtCl2 |
[A] |
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COMe |
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+ |
Cl |
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F |
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20−48 h |
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n-Bu |
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SiMeCl2 |
[C] |
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F |
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Cl |
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CF3 |
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n-Hex |
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SiMeCl2 |
[C] |
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Cl |
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CN |
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[A]0.5% PdCl2(i-Pr3P)2, KF (6 equiv), DMF, 120 °C
[B]2.0% PdCl2(Cy2PCH2CH2PCy2), KF (10 equiv), DMF, 120 °C
[C]0.5% [PdCl(η3-C3H5)]2, TBAF (3.6 equiv), THF, 90 °C in a sealed tube
coupling product
58−97%
Scheme 15
III.2.4 OVERVIEW OF OTHER Pd-CATALYZED CROSS-COUPLING PROTOCOLS |
293 |
The role of a fluoride ion as an activator and as a ligand on silicon can be played by a hydroxide ion and a chloride ligand, respectively.[21] Thus, the Pd-catalyzed coupling of aryland alkenylchlorosilanes with aryl and alkenyl halides was accomplished in the presence of NaOH under mild conditions (Scheme 16).
R1 |
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SiR2Cl2 |
Br |
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F |
X |
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R1 = H, MeO, Me, |
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F |
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COMe |
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trans-4-n-Pr-cyclohexyl |
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X |
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COMe |
Br |
CN |
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R2 = Et, Me |
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+ |
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N |
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R3 |
SiMeCl2 |
X |
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R3 = n-Bu, Me3Si |
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Me |
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CF3 |
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n-Hex |
SiEtCl2 |
Br |
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Cl |
CF3 |
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I |
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n-Hex |
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CF3 |
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X = I, Br, Cl |
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0.5−2.5% Pd(OAc)2, Pd(OAc)2/2PPh3 or PdCl2(i-Pr3P)2 |
coupling |
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NaOH (6.0 equiv) |
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product |
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55−95% |
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THF or benzene, 60−80 °C, 5−62 h |
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Scheme 16
Allyl carbonates (Schemes 17 and 18) and diene monoxides (Scheme 19) were also employed in the Pd-catalyzed coupling reaction of aryland alkenylsilanes.[22],[23] The reaction does not require activation by a fluoride ion or an additional base like a hydroxide ion.
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5% Pd(OAc)2 |
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R1 |
+ R2OCOO |
Ph |
5% PPh3 |
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SiMen F3-n |
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DMF, 60 |
°C, 1−28 h |
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R1 = n-Hex, Ph |
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2 |
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R |
= Et, i-Pr |
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R1 |
Ph |
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n = 1, 2 |
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Ph |
EtOCOO |
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72−94% |
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+ |
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SiMeF2 |
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Ph |
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+ |
Ph |
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1 |
: |
4.4 |
76% |
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EtOCOO |
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Ph |
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Ph |
+ |
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+ |
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PhCH2O |
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PhCH2O |
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PhCH2O |
80% |
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2.5 |
: |
1 |
|
Scheme 17
294 |
III |
Pd-CATALYZED CROSS-COUPLING |
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||||||||||||
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2.5% Pd2(dba)3 • CHCl3 |
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Ar −SiEtF2 |
+ EtOCOO |
Ph |
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5% PPh3 |
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Ar |
Ph |
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benzene, 60 °C |
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Ar = Ph |
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84−97% |
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2-thienyl |
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2,5-(MeO)2C6H3 |
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4-Me-C6H4 |
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Ph |
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Ph−SiEtF2 |
EtOCOO |
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Ph |
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+ |
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Ph |
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1 : |
10 |
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93% |
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EtOCOO |
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Ph |
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+ |
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52% |
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EtOCOO |
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Ph |
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+ |
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33% |
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EtOCOO |
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Ph |
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+ |
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40% |
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Scheme 18 |
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O |
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Ph |
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2.5% Pd2(dba)3 • CHCl3 |
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SiMeF2 |
|
10% P(OCH2)3CEt |
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benzene, 40 °C |
Ph |
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Ph |
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OH |
+ |
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OH |
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5.9 |
: |
1 |
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59% |
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O |
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2.5% Pd2(dba)3 • CHCl3 |
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Ar−SiEtF2 |
5% PPh3 |
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benzene, 40−60 °C |
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Ar = Ph |
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Ar |
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Ar |
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+ |
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2-thienyl |
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OH |
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2,5-(MeO)2C6H3 |
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1−7.1 |
: 1 |
OH |
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4-Me-C6H4 |
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51−67% |
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Scheme 19