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. 2025 Apr 30;147(17):14163-14173.
doi: 10.1021/jacs.4c15596. Epub 2025 Apr 17.

The Role of Boron Reagents in Determining the Site-Selectivity of Pyridine(dicarbene) Cobalt-Catalyzed C-H Borylation of Fluorinated Arenes

Haozheng Li  1 , Hanna H Cramer  1 , Jose B Roque  1 , Carlota Odena  1 , Alex M Shimozono  1 , Paul J Chirik  1
Affiliations

The Role of Boron Reagents in Determining the Site-Selectivity of Pyridine(dicarbene) Cobalt-Catalyzed C-H Borylation of Fluorinated Arenes

Haozheng Li et al. J Am Chem Soc. .

Abstract

The origin of the meta- and ortho-to-fluorine site-selectivity in the C(sp2)-H borylation of fluorinated arenes with B2Pin2 and HBPin promoted by pyridine(dicarbene)cobalt catalysts has been investigated. In situ generation of the cobalt(I)-boryl complex and treatment with three representative fluoroarenes established meta-selective C(sp2)-H oxidative addition to form predominantly the meta isomers of the corresponding cobalt(I)-aryl complexes. Attempts to observe or isolate the four-coordinate cobalt(I)-boryl complex yielded the cobalt-hydride dimer, [(iPrACNC)CoH]2, borohydride (iPrACNC)CoH2BPin, or diboryl hydride, (iPrACNC)CoH(BPin)2 depending on the amounts of B2Pin2 and HBPin present. The phosphite derivatives (iPrACNC)CoH(P(OiPr)3) and (iPrACNC)CoBPin(P(OiPr)3) were prepared and crystallographically characterized. In the catalytic borylation of 1,3-difluorobenzene, ortho-to-fluorine cobalt(I)-aryl and borohydride complexes were identified as resting states despite meta-to-fluorine borylation being the major product of catalysis. Deuterium kinetic isotope effects support irreversible but not turnover-limiting C(sp2)-H oxidative addition. Stoichiometric borylation of isolated cobalt(I)-aryl intermediates with B2Pin2 established that the meta-cobalt(I)-aryl was more reactive than the ortho-isomer and accounts for the observed cobalt(I)-aryl resting states. All cobalt(I)-aryl compounds reacted more quickly with HBPin. While ortho-cobalt(I)-aryl compounds yielded arylboronate products with high site-selectivity, meta-cobalt-aryl counterparts yielded a mixture of arylboronate isomers and free arene. Deuterium labeling experiments with DBPin confirmed that HBPin mediates reversible C(sp2)-H oxidative addition. Thus, the overall site-selectivity arises from two reinforcing effects: (i) kinetically meta-selective oxidative addition and (ii) faster reaction of the meta-cobalt-aryl isomer with B2Pin2. As B2Pin2 is converted to HBPin, C(sp2)-H reductive elimination competes against borylation of the meta-cobalt-aryl isomer, resulting in increased ortho-selective borylation.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Solid-state structure of (iPrACNC)CoH(P(OiPr)3) at 30% probability ellipsoids. Hydrogen atoms omitted for clarity.
Figure 2.
Figure 2.
Resting state analysis during the catalytic borylation of 1a with 1 equivalent of B2Pin2 in THF-d8. Yields of 2a and cobalt resting states were determined by 1H and 19F NMR spectroscopies, respectively using 1,4-bis(trifluoromethyl)benzene as an internal standard.
Figure 3.
Figure 3.
Calculated Gibbs free energy profile for the oxidative addition of 1a to (iPrACNC)CoBPin and formation of cobalt(I) aryl products.
Scheme 1.
Scheme 1.. Pincer effects in cobalt-catalyzed C(sp2)–H borylation to promote ortho versus meta selective reactions of 1-fluoro-3-(trifluoromethyl)benzene.,
Scheme 2.
Scheme 2.. (A) Representative example of switchable site-selectivity in the cobalt-catalyzed borylation of fluoroarenes. (B) Site-selectivity of C(sp2)–H oxidative addition with (iPrACNC)CoR1 and isomerization. (C) Understanding the origin of site-selectivity in cobalt-catalyzed C(sp2)–H borylation of fluoroarenes (this work).
Scheme 3.
Scheme 3.. Synthesis of (A) cobalt(I)-borohydride and (B) hydride complexes.
Scheme 4.
Scheme 4.. Reactivity of [(iPrACNC)CoH]2 with P(OiPr)3 and Arenes.
Scheme 5
Scheme 5. (A) Observation of the equilibrium between (iPrACNC)CoH2BPin and (iPrACNC)CoH(BPin)2 in THF-d8 at 23 °C. (B) Trapping of (iPrACNC)CoH(BPin)2 by triisopropyl phosphite and solid-state structure of (iPrACNC)Co(BPin)(P(OiPr)3) at 30% probability ellipsoids with hydrogen atoms omitted for clarity.
.
Scheme 6.
Scheme 6.. Site-selectivity of C(sp2)–H oxidative addition activation from in-situ generated (iPrACNC)CoBPin by borylation of cobalt(I)-aryl intermediates with B2Pin2.
Scheme 7.
Scheme 7.. Measurement of (A) parallel and (B) competition deuterium kinetic isotope effects for the borylation of 1a with (iPrACNC)CoCH3 using B2Pin2.
Scheme 8.
Scheme 8.. Stoichiometric borylation of isomers of Co-1a with B2Pin2.
Scheme 9.
Scheme 9.. Stoichiometric borylation of isomers of Co-1a isomers with HBPin.
Scheme 10.
Scheme 10.. Proposed mechanisms to account for the differences in chemoselectivity between B2Pin2 and HBPin and between 3,5- and 2,6-Co-1a isomers.
Scheme 11.
Scheme 11.. Deuterium labeling experiments with 2 equivalents of DBPin under catalytic conditions.
Scheme 12.
Scheme 12.. Catalytic and stoichiometric borylation of 1c in the presence of DBPin.
Scheme 13.
Scheme 13.. Origins of meta-selective cobalt-catalyzed borylation.
Scheme 14.
Scheme 14.. Origin of ortho-selective cobalt-catalyzed borylation with HBPin.
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