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. 2024 May 20;43(11):1208-1212.
doi: 10.1021/acs.organomet.4c00174. eCollection 2024 Jun 10.

A Hydrazone Ligand for Iridium-Catalyzed C-H Borylation: Enhanced Reactivity and Selectivity for Fluorinated Arenes

Christopher D Peruzzi  1 , Susanne L Miller  1 , Jonathan E Dannatt  1   2 , Behnaz Ghaffari  1 , Robert E Maleczka Jr  1 , Milton R Smith 3rd  1
Affiliations

A Hydrazone Ligand for Iridium-Catalyzed C-H Borylation: Enhanced Reactivity and Selectivity for Fluorinated Arenes

Christopher D Peruzzi et al. Organometallics. .

Abstract

Ir-catalyzed C-H borylations of fluorinated and cyanated arenes with high meta-to-F/CN are described. Use of a dipyridyl hydrazone framework as the ancillary ligand and pinacolborane (HBpin) as the functionalizing reagent generates catalysts that are significantly more active and selective than 4,4'-di-tert-butyl-2,2'-bipyridine (dtbpy) for both electron-deficient and electron-rich substrates. Investigation of the ligand framework resulted in the observation of formal N-borylation of the hydrazone by HBpin, as evidenced by NMR spectroscopy and X-ray crystallography. Subsequent stoichiometric reactions of this adduct with an iridium precatalyst revealed the formation of an unusual IrI hydrazido. Isolation and use of this hydrazido reproduce the selectivity of in situ generated catalysts, suggesting that it leads to formation of the active species.

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Conflict of interest statement

The authors declare the following competing financial interest(s): S.L.M., M.R.S., and R.E.M. own a percentage of BoroPharm, Inc.

Figures

Scheme 1
Scheme 1. Challenges in Selective Fluoroarene Functionalizations
Scheme 2
Scheme 2. Optimization of Borylation Conditions
Reaction conditions: fluoroarene (1.0 mmol), HBpin (2.0 mmol) or B2pin2 (1.0 mmol), [Ir(OMe)cod]2 (1.0 mol %), ligand (2.0 mol %), solvent (2.0 mL). n-Hexane used as solvent. CH2Cl2 used as solvent. Reaction run at 40 °C.
Scheme 3
Scheme 3. Investigation of the Hydrazone Ligand Framework
Molecular structure displayed with 50% probability ellipsoids and a partial labeling scheme (cocrystallized CH3CN and H2O omitted for clarity). N1–B1 = 1.520 Å, N3–B1 = 1.587 Å.
Scheme 4
Scheme 4. Borylation of Fluorochlorobenzene with Isolated Adduct and IrI Hydrazido
See the Supporting Information for full details on the experimental procedures.
See this image and copyright information in PMC

References

    1. Ros A.; Fernández R.; Lassaletta J. M. Functional Group Directed C–H Borylation. Chem. Soc. Rev. 2014, 43 (10), 3229–3243. 10.1039/C3CS60418G. - DOI - PubMed
    1. Robbins D. W.; Boebel T. A.; Hartwig J. F. Iridium-Catalyzed, Silyl-Directed Borylation of Nitrogen-Containing Heterocycles. J. Am. Chem. Soc. 2010, 132 (12), 4068–4069. 10.1021/ja1006405. - DOI - PubMed
    1. Kawamorita S.; Ohmiya H.; Sawamura M. Ester-Directed Regioselective Borylation of Heteroarenes Catalyzed by a Silica-Supported Iridium Complex. J. Org. Chem. 2010, 75 (11), 3855–3858. 10.1021/jo100352b. - DOI - PubMed
    1. Ishiyama T.; Isou H.; Kikuchi T.; Miyaura N. Ortho-C-H Borylation of Benzoate Esters with Bis(Pinacolato)Diboron Catalyzed by Iridium-Phosphine Complexes. Chem. Commun. 2010, 46 (1), 159–161. 10.1039/B910298A. - DOI - PubMed
    1. Roosen P. C.; Kallepalli V. A.; Chattopadhyay B.; Singleton D. A.; Maleczka R. E. Jr.; Smith M. R. III Outer-Sphere Direction in Iridium C-H Borylation. J. Am. Chem. Soc. 2012, 134 (28), 11350–11353. 10.1021/ja303443m. - DOI - PMC - PubMed

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