Ir(I)-Catalyzed C–H Borylation

Josephine Nakhla, Market Segment Manager Organometallics and Catalysis

Merck

Arylboronic acids and esters are used for a variety of transformations, most notably the Suzuki-Miyaura cross-coupling reaction. This reaction is used to selectively construct C–C bonds through the combination of an organo-boron nucleophile with a suitable aryl, alkenyl, or alkyl halide or triflate. While the Suzuki-Miyaura reaction has become commonplace within the synthetic community, one limitation of this method is the limited ability to access the requisite organo-boron species.

Historically, methods for the synthesis for aryl C–B bonds have relied upon the use of harshly basic reaction conditions or substrates containing prefunctionalized carbon centers. These shortcomings require additional steps to either protect sensitive functionality or install the necessary functional handle prior to C–B bond formation (Figure 1).

Figure 1. Classical methods for C–B bond formation

The direct formation of aryl C–B bonds from aryl C–H bonds thus represents a powerful strategy for streamlining the synthesis of these useful reagents (Figure 2).¹

Figure 2. Metal-catalyzed direct C–H borylation

Building upon their previous work within the area,² Professor John F. Hartwig has disclosed a method for the direct conversion of aryl C–H bonds to aryl C–B bonds through the use of an Ir(I) catalyst and B₂pin₂ (Figure 3).³ This powerful system displays excellent regioselectivity that can be easily predicted by sterics and leads to the rapid synthesis of highly useful arylboronic esters.

Figure 3. Ir(I)-Catalyzed aryl C–H borylation

This method provides a simple and direct route to arylboronic esters that fully avoids the use of harshly basic reaction conditions and does not require multiple reaction steps and manipulations. Importantly, this reaction employs catalysts and reagents that are all readily accessible and commerically available.

References

1. Cho J. 2002. Remarkably Selective Iridium Catalysts for the Elaboration of Aromatic C-H Bonds. 295(5553):305-308. https://doi.org/10.1126/science.1067074

2. Chen H, Hartwig J. 1999. Catalytic, Regiospecific End‐Functionalization of Alkanes: Rhenium‐Catalyzed Borylation under Photochemical Conditions Angewandte Chemie International Edition. 38(22):3391-3393 .

3. Chen H. 2000. Thermal, Catalytic, Regiospecific Functionalization of Alkanes. 287(5460):1995-1997. https://doi.org/10.1126/science.287.5460.1995

4. Boller TM, Murphy JM, Hapke M, Ishiyama T, Miyaura N, Hartwig JF. 2005. Mechanism of the Mild Functionalization of Arenes by Diboron Reagents Catalyzed by Iridium Complexes. Intermediacy and Chemistry of Bipyridine-Ligated Iridium Trisboryl Complexes. J. Am. Chem. Soc.. 127(41):14263-14278. https://doi.org/10.1021/ja053433g

5. Mkhalid IAI, Barnard JH, Marder TB, Murphy JM, Hartwig JF. 2010. C?H Activation for the Construction of C?B Bonds. Chem. Rev.. 110(2):890-931. https://doi.org/10.1021/cr900206p