Generation of Diversity Sets with High sp³ Fraction Using the Photoredox Coupling of Organotrifluoroborates and Organosilicates with Heteroaryl/Aryl Bromides in Continuous Flow

Abstract

The photoredox cross-coupling of aryl halides and potassium alkyl trifluoroborates is a very effective means to form Csp-Csp bonds. However, this transformation is inefficient for the coupling of unactivated primary trifluoroborates. We have developed a generally useful, continuous flow Csp-Csp coupling procedure for the synthesis of diverse product sets that is compatible with both trifluoroborates and silicate reagents. This universal protocol provides diversity sets from both primary and secondary coupling partners. This easily scalable procedure widens the substrate scope of the coupling reaction and is efficient for producing a greater range of analogues bearing a high sp fraction.

Multigram Synthesis of Heterabicyclo[n.1.0]alkan‐1‐yl Trifluoroborates

“…Building blocks providing new C–C bonds are relatively rarer; typically, they are organoboron derivatives which have gained momentum with recent advances in sp 2 ‐sp 3 couplings [12–15] . Molander's photoredox and related methodologies are excellent examples of introducing building blocks of type 1 (X = BF 3 – K + ) into such transformations (Figure 1); [16–21] however, building blocks 1 have low reactivity under other commonly used C–C coupling conditions. An alternative approach that steps back to classical palladium‐catalyzed couplings involves partially unsaturated reagents of general structure 2 , which are highly effective in e.g.…”

Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry

“…[85] Two years later, the same group described an optimized protocol that also worked well for secondary trifluoroborates as the coupling partners (Scheme 19). [86] The procedure commenced with the preparation of a single stock solution containing an aryl halide, a Ni precatalyst, a ligand, and an Ir photocatalyst in dimethylacetamide (DMA). This solution was then added to vessels charged with solid alkyl trifluoroborate.…”

Synthesis of Aliphatic Amides through a Photoredox Catalyzed Radical Carbonylation Involving Organosilicates as Alkyl Radical Precursors

“…They are interesting for their ease of synthesis from the corresponding alkoxysilane or trichlorosilane and for their ability to generate unstabilized primary alkyl radicals, under photoredox‐catalyzed conditions, whether in the presence of classical Ru(II) or Ir(III) photocatalysts or even with an organic dye . The nucleophilic radicals thus formed can be readily engaged in C−C bond formation by addition to various species such as activated alkenes, allylsulfones, imines or recently heteroarenes and N‐acylhydrazone or by nickel catalyzed cross coupling reactions …”