Cross-Coupling Reactions of Alkylsilicates

The reaction of the alkylsilicates with aryl bromides under the influence of a Ni^II catalyst and the photoredox agent Ru(bpy)₃(PF₆)₂ gave the alkylated aryl in 0 to 94% yields with methyl, chloromethyl and an epoxy functional system (when reacted with 4-phenyl-1-bromobenzene) all giving low or no yield (Scheme 3).³

As an example of the ability to tolerate the amine functionality the 3-aminopropylsilicate (as the ammonium salt) was reacted with a variety of (het)aryl bromides under the conditions above to provide the aminopropyl-derivatized (het)aryl systems in good yield (Scheme 4). The reaction demonstrated tolerance for CN, CO₂Me, HNCOMe, OH, and CF₃ groups.³

A comparison study of the single-electron-transfer oxidation of trifluoroborates and silicates has been reported. In general both species are able to generate C-centered radicals, although the trifluoroborates were slightly better with Fukuzumi catalyst 3.⁴

The photoredox dual catalysis was applied to the alkylation of vinyl bromides and iodides. Even the typically less reactive vinyl chlorides were found to react. For example, when the 3-acetoxypropylsilicate 4 was reacted with a series of vinyl bromides excellent results in the sp³-sp² cross-coupling took place (Scheme 5). The yields were good to excellent with the lone exception of a hydroxyl derivative that gave 0% coupling product, although the corresponding TBS ether reacted very well. A variety of alkylsilicates were reacted with vinyl bromides (15 examples: 0 – 94%) and vinyl iodides as well (12 examples: 27 – 86%).⁵

A Vertex group reported on a continuous flow approach to the photoredox coupling of alkyltrifluoroborates and alkylsilicates. With a flow rate of 0.5 mL/min sp³-sp² cross coupling with (het)aryl bromides was accomplished in a reaction time of 40 minutes versus 18 hours in a batch approach. The yields were excellent and the process scalable to larger levels (Scheme 6). The approach enables rapid parallel syntheses for library and diversification generation.⁶

The Molander group also contributed to the alkylsilicate cross-coupling arena showing that derivatized phenols could be cross-coupled with the silicates (Scheme 7). Thus, triflates, mesylates and tosylates were all successfully cross-coupled. Amine-functional alkylsilicates failed to react. In comparison, an aryl bromide proved to be more reactive than the corresponding aryl triflate.⁷