The goal of the early work in the use of organosilanes as the organometallic component in the cross-coupling reactions was to take advantage of the polarizing and activating effect of fluorine ligands on the silicon atom. Thus, phenyltrifluorosilane couples with aryl bromides in modest to good yield.
The presence of a fluorine ligand on silicon aids in the coupling of the silane in various cross-coupling applications. For instance, (Z)-1-(fluorodimethylsilyl)-1-decene is coupled with (Z)-1-iodo-1-decene in good yield to form the corresponding Z,Z-diene (Eq. 1).19
Vinylpentafluorosilicates undergo Heck coupling reactions (Eq. 2).20 This system also couples well with allyl chloride (Eq. 3).20 The tetrabutylammonium triphenyldifluorosilicate cross-coupling with aryl bromides or chlorides is also possible, with bromides being the more reactive electrophilic component (Eq. 4).21
Alkenyldimethylfluorosilanes, readily prepared from the corresponding esters, cross-couple with vinyl and aryl iodides under the influence of fluoride ion promotion (Eqs. 5, 6).22
Cyclopropyltrifluorosilanes can be prepared by cyclopropanation of a vinyltrichlorosilane, in turn available via hydrosilylation of an acetylene. These cyclopropyltrifluorosilanes were shown to cross-couple with aryl bromides to give the arylcyclopropane in good yields (Eq. 7).23 This is a good example of an sp3 organosilane cross-coupling.
Cross-coupling of aryltrifluorosilanes with secondary alkyl bromides and iodides occurs in good yields (Eq. 8).24
The coupling of an alkyltrifluorosilane with aryl bromides gives good yields of the alkylated aromatic ring.25 The reaction was shown to be regioselective with 2,3-dibromofurans and 2,3-dibromopyridine (Eqs. 9, 10).
Nickel in combination with an amino alcohol ligand, for example norephedrine, was found to provide the most versatile and efficient catalyst for Hiyama cross-coupling reactions of alkyl electrophiles with aryltrifluorosilanes that has been described to date. Unprecedented Hiyama reactions of activated secondary alkyl bromides were achieved, as were the first Hiyama couplings of activated alkyl chlorides (Eqs. 11, 12).26
Trimethylvinylsilanes can be used to directly vinylate aryl and vinyl iodides in moderate to excellent yields as shown in Eqs. 13-16.27 The allylpalladium chloride dimer, APC, is an excellent catalyst for these reactions. Ethynyltrimethylsilanes undergo Sonogashira-type cross-coupling reactions to form enynes (Eq. 17) and allyltrimethylsilane can lead to 1,4-dienes (Eq. 18) or 1,5-dienes (Eq. 19) when cross-coupled with vinyl halides or allyl halides, respectively.27
A study of the reactivities of β-silylethylcarbazole showed that the triethoxysilyl group is more effective in the cross- coupling with aryl iodobenzene than either the phenyldimethylsilyl or trimethylsilyl derivatives (Eq. 20).28
Aryltrimethylsilanes can be cross-coupled with aryl bromides after first being converted to the dichloroborane (Eq. 21).29 This approach, which really uses the boronic acid Suzuki methodology, provides a clean, in-situ route to the arylboronic acid derivative.
o-Fluoro-, chloro- or methoxyphenyltrimethylsilanes undergo efficient cross-coupling reactions with aryl iodides transferring the o-aryl substituent (Eq. 22).30 2-Allyldimethylsilylpyridine cross-couples the 2-pyridyl group with aryl iodides (Eq. 23).31 ln this reaction the allyl group serves as a source of the silanol functionality, the reactive silyl intermediate in the cross-coupling step.
The significant difference in the reactivity of the C-H bond versus the C-Si bond in the cross-coupling reactions of ethynyltrimethylsilane allows for the facile stepwise preparation of asymmetrical diarylacetylenes (Eq. 24).32
The synthesis of a key intermediate conjugated tetraene in the total synthesis of RK-397, a polyene macrocycle, was accomplished taking advantage of the sequential, selective silicon-based cross-coupling steps to prepare a key difunctional conjugated tetraene. Thus, the dimethylsilanol moiety cross-couples in the absence of fluoride promotion whereas the benzyldimethylsilyl unit requires fluoride activation (Eq. 25).33
Advantage was taken of the excellent stability of the benzyldimethylsilyl group in a cross-coupling step in the synthesis of fostriecin, a cyctotoxic phosphate ester (Eq. 26).34 The reaction conditions required demonstrate the potential drawback of the protocols that require fluoride promotion in that the silyl protecting groups are removed under the reaction conditions.
The cesium fluoride-catalyzed direct pentafluorophenylation of a 2-trimethylsilylthiophene proved possible (Eqs. 27, 28).35 lt is advantageous to block the 5 position of the thiophene to avoid a side reduction reaction.
Various trimethylsilylated thiophenes cross-couple at the 5-C-H site rather than the C-Si site under conditions in which fluoride ion is not involved (Eq. 29).36
Esters, ketones, mono-protected primary amines, and ethers are tolerated in the cross-coupling of alkenylsilanes with aryl iodides (Eqs. 30, 31).37 Several of the vinylsilane systems employed in the study are shown below. The nature of the functional group influences the regiochemistry of the coupling step.
The phenyldimethylsilyl group can be utilized in cross-coupling reactions, but first the phenyl group must be converted to a silanol derivative, which then undergoes the cross-coupling reaction (Eq. 32).38 The reaction sequence was applied to the synthesis of matairesionol.
Advantage can be taken of the facile fluorodebenzylation of benzylsilanes to use benzyldimethylsilyl groups in cross-coupling reactions utilizing organosilanes.39-40 Examples of this approach are shown in Eqs. 33, 34, 35. ln these reactions the active silane species is the fluorosilane.
ln a similar manner the aryl or vinyl silacyclobutanes under the influence of fluoride ion cross-couple well with aryl iodides (Eqs. 36-38).42,43 It has been shown that due to the ring strain the silacyclobutane unit is a precursor to the reactive silanol functionality in these reactions.