C-H Functionalization

The selective functionalization of carbon-hydrogen bonds is an emerging method in organic synthesis and is attractive for the synthesis of new synthetic building blocks as well as late stage functionalization. Because carbon-boron bonds are among the most versatile in synthesis, C-H borylation methods are both highly attractive and powerful. Use of electron donating pyridine bis(phosphine) pincers has enabled two-electron redox chemistry at cobalt and enabled highly active and selective catalysts for the borylation of C(sp2)-H bonds (J. Am. Chem. Soc. 2014, 136, 4133.). With relatively electron rich arenes and pyridines, mechanistic studies support C-H oxidative addition as the turnover limiting step promoted by a cobalt(I)-boryl (J. Am. Chem. Soc. 2016, 138, 10645.). Unprecedented electronic sensitivity has also been observed and the cobalt catalyst can distinguish between subtle differences in pKas of C(sp2)-H bonds in fluorinated arenes opening promising new pathways to drug molecules and agrochemicals (J. Am. Chem. Soc. 2017, ASAP.). A number of other electron donating ligands have also been evaluated for cobalt catalyzed C(sp2)-H borylation (Organometallics 2015, 34, 1307.), leading to the discovery of readily available, air-stable terpyridine Cobalt bis(acetate) precatalysts effective for this transformation (Organometallics 2017, 36, 142.).

Altering the selectivity of metal-catalyzed borylation from C(sp2)-H to C(sp3)-H bonds without the use of directing groups is a long-standing challenge in catalysis and organic synthesis. Cobalt(II) and nickel(II) complexes supported by potentially redox-active α-diimine ligands promote the selective borylation of benzylic C(sp3)-H bonds in arenes over the more common C(sp2)-H aromatic sites (J. Am. Chem. Soc. 2016, 138, 766.; J. Am. Chem. Soc. 2017, ASAP.). Another interesting feature of this chemistry is the conversion of multiple C-H bonds on a methyl group to C-B bonds. Air stable catalyst variants have been realized and current efforts are focused on exploration of the polyborylated products in organic synthesis as well as understanding the nature of this unusual catalytic process.

Selected Publications

Cobalt-Catalyzed C(sp2)–H Borylation with an Air-Stable, Readily Prepared Terpyridine Cobalt(II) Bis(acetate) Precatalyst
Nadia G. Léonard, Máté J. Bezdek, and Paul J. Chirik
Organometallics 2017, 36, 142-150.

Cobalt-Catalyzed C(sp2)-H Borylation: Mechanistic Insights Inspire Catalyst Design
Jennifer V. Obligacion, Scott P. Semproni, Iraklis Pappas and Paul J. Chirik
J. Am. Chem. Soc. 2016, 138, 10645-10653.

Cobalt-Catalyzed Benzylic Borylation: Enabling Polyborylation and Functionalization of Remote, Unactivated C(sp3)–H Bonds
W. Neil Palmer, Jennifer V. Obligacion, Iraklis Pappas, and Paul J. Chirik
J. Am. Chem. Soc. 2016, 138, 766-769.

Cobalt-Catalyzed C–H Borylation
Jennifer V. Obligacion, Scott P. Semproni, Paul J. Chirik
J. Am. Chem. Soc. 2014, 136 (11), 4133-4136.