Technical Library

The now well-known cross-coupling of sp-sp2 and sp2-sp2 carbon centers has proved to be highly useful in synthetic organic chemistry. Lacking in the various C-C cross-coupling arsenal is the ability to couple sp3-sp2 and sp3-sp3 carbon centers. The Molander group at the University of Pennsylvania was the first to employ a photoredox/Ni dual catalysis approach to the resolution of this omission (Scheme 1). A general method for the coupling of sp3-sp2 carbon centers is particulary important for drug discovery as it has been reported that compounds with lower sp3 fractions have higher rates of attrition in drug development.1 Their first attempts were to use a metal photoredox catalyst and an alkyltrifluoroborate as the radical provider. The second catalyst was a Ni0 complex, which reacts with the radical generating a NiI intermediate. This then undergoes an oxidative addition of the aryl or vinyl halide to form a NiIII intermediate, followed by a reductive elimination to NiI and the cross-coupled product. This work was followed by both Fensterbank and Molander utilizing alkylbis(catecholato)silicates as the alkyl radical source. A summary of that chemistry is the topic of this review. The photoredox-catalyzed, nickel-based cross-coupling of alkylsilicates and alkyltrifluoroborates has been reviewed.2

In the interest of space and repetition the two commonly used silicates are generalized in structures 1 for the triethylammonium silicate moiety and 2 for the diisopropylammonium silicate moiety . Thus the abbreviations Si and Si* are used for the triethylammonium and diisopropylammonium silicate, respectively, throughout this review.

Scheme 1

The introduction of the use of alkylbis(catecholato)silanes was brought about by the observation that the oxidation potential (E0 for these species is +0.34 V vs SCE for R = primary alkyl) is well below the E0 for photoexcited Ir or Ru catalyst (E0 = +1.32 V vs SCE) as well as those for certain organic dyes. The Ir-based photocatalyst is very expensive, and Molander was able to replace it with a less costly Ru compound. The alkylbis(catecholato)silanes are readily prepared from the appropriate alkyltrimethoxysilane via reaction with a substoichiometric amount of catechol and either triethylamine or diisopropylamine (Scheme 2). Isolated yields of the alkylsilicates from this readily scaled procedure are in the high 80 to mid 90% range. The alkylbis(catecholato) silanes are air stable solids that can be stored for long periods of time.3 Gelest offers a wide range of alkylsilicates and can also make custom versions upon request.