Iridium-catalyzed C–H borylation of quinolines and unsymmetrical 1,2-disubstituted benzenes: insights into steric and electronic effects on selectivity

  title={Iridium-catalyzed C–H borylation of quinolines and unsymmetrical 1,2-disubstituted benzenes: insights into steric and electronic effects on selectivity},
  author={Hazmi Tajuddin and Peter Harrisson and Bianca Bitterlich and Jonathan C. Collings and Neil Sim and Andrei S. Batsanov and Man Sing Cheung and Soichiro Kawamorita and Aoife C. Maxwell and Lena Shukla and James Alan Morris and Zhenyang Lin and Todd B. Marder and Patrick G. Steel},
  journal={Chemical Science},
Borylation of quinolines provides an attractive method for the late-stage functionalization of this important heterocycle. The regiochemistry of this reaction is dominated by steric factors but, by undertaking reactions at room temperature, an underlying electronic selectivity becomes apparent, as exemplified by the comparative reactions of 7-halo-2-methylquinoline and 2,7-dimethylquinoline which afford variable amounts of the 5- and 4-borylated products. Similar electronic selectivities are… 
118 Citations

Metal-Free Borylation of Heteroarenes Using Ambiphilic Aminoboranes: On the Importance of Sterics in Frustrated Lewis Pair C-H Bond Activation.

Two novel frustrated Lewis pair aminoboranes were synthesized, and their structural features were elucidated both in solution and in the solid state, and it was shown that 2 and 3 are more active catalysts for the borylation of heteroarenes than the bulkier analogue 1.

Iridium-catalyzed C-H borylation of heteroarenes: scope, regioselectivity, application to late-stage functionalization, and mechanism.

One-pot functionalizations are reported of the hetero Daryl boronate esters formed in situ, demonstrating the usefulness of the reported methodology for the synthesis of complex heteroaryl structures.

Mechanistic Investigation of Iridium-Catalyzed C–H Borylation of Methyl Benzoate: Ligand Effects in Regioselectivity and Activity

The Ir-catalyzed C–H borylation of methyl benzoate has been studied with DFT methodology in order to understand the experimentally observed ligand-induced regioselectivity and activity when different

para-C-H Borylation of Benzene Derivatives by a Bulky Iridium Catalyst.

The present [Ir(cod)OH]2/Xyl-MeO-BIPHEP catalyst represents a unique, sterically controlled, para-selective, aromatic C-H borylation system that should find use in streamlined, predictable chemical synthesis and in the rapid discovery and optimization of pharmaceuticals and materials.

The directing group wins over acidity: kinetically controlled regioselective lithiation for functionalization of 2-(2,4-dihalophenyl)-1,3-dithiane derivatives.

Computer calculated pKa values of the available reactive site protons and the experimental results suggest that the regioselective lithiation in 2-(2,4-dihalophenyl)-1,3-dithiane derivatives is not governed by thermodynamic acidity but exclusively dictated by the kinetic removal of protons due to cooperative coordination (complex induced proximity effect, CIPE).

Theoretical investigations of the Ir-catalyzed direct borylation of B(3,6)–H of o-carborane: the actual catalyst, mechanism, and origin of regioselectivity

The very recent success of Xie et al. (Nat. Commun., 2017, 8, 14827) in achieving the Ir-catalyzed direct borylation of the cage B(3,6)–H of o-carboranes with excellent yield and regioselectivity

Iridium-catalyzed C-H borylation of pyridines.

The iridium-catalysed C-H borylation is a valuable and attractive method for the preparation of aryl and heteroaryl boronates but can be challenged by low reactivity and propensity for rapid protodeborylation, particularly for a bor onate ester ortho to the azinyl nitrogen.

Flexible Reaction Pocket on Bulky Diphosphine–Ir Complex Controls Regioselectivity in para-Selective C–H Borylation of Arenes

We used DFT calculations to elucidate the mechanism and source of regioselectivity for Ir-catalyzed para-selective C–H borylation with the bulky Xyl-MeO-BIPHEP diphosphine ligand (L1). We found that

Rhodium-Catalyzed Intermolecular C–H Silylation of Arenes with High Steric Regiocontrol

A catalytic intermolecular C–H silylation of unactivated arenes that manifests very high regioselectivity through steric effects of substituents meta to a potential site of reactivity is reported.

Late-Stage Functionalization of 1,2-Dihydro-1,2-azaborines via Regioselective Iridium-Catalyzed C-H Borylation: The Development of a New N,N-Bidentate Ligand Scaffold.

The 6-[pyrid-2-yl]-B-Me-1,2-azaborine ligand has been demonstrated to form an emissive coordination complex with dimesitylboron that exhibits bathochromically shifted absorption and emission maxima and a higher photoluminescence quantum yield compared to its carbonaceous analogue.



C-H arylation of pyridines: high regioselectivity as a consequence of the electronic character of C-H bonds and heteroarene ring.

The new protocol expands the scope of catalytic azine functionalization as the excellent regioselectivity at the 3- and 4-positions well complements the existing methods for C-H arylation and Ir-catalyzed borylation, as well as classical functionalization of pyridines.

Mild iridium-catalyzed borylation of arenes. High turnover numbers, room temperature reactions, and isolation of a potential intermediate.

It is reported that Ir(I) precursors in conjunction with bipyridine ligands catalyze in high yields the borylation of arenes under mild conditions, and that the reactions involve uncommon, Ir(II) tris-boryl complexes.

Cyanation of arenes via iridium-catalyzed borylation.

The utility of this methodology is demonstrated through the conversion of a protected 2,6-disubstituted phenol to 4-cyano-2, 6-dimethylphenol, which is an intermediate in the synthesis of the pharmaceutical etravirine.

Iridium complexes of N-heterocyclic carbenes in C–H borylation using energy efficient microwave technology: influence of structure, ligand donor strength and counter ion on catalytic activity

Bridged and unbridged N-heterocyclic carbene (NHC) ligands were metalated with [Ir(COD)Cl]2 to give iridium(I) mono- and biscarbene substituted catalysts [Ir(COD)NHC(Cl)] and [Ir(COD)(NHC)2][X] (X:

Meta halogenation of 1,3-disubstituted arenes via iridium-catalyzed arene borylation.

The utility of this methodology was demonstrated by the formal conversion of nicotine to Altinicline in three steps with an overall yield of 61% using meta bromination of nicotine as the first step.

Experimental and computational evidence for a boron-assisted, sigma-bond metathesis pathway for alkane borylation.

It is shown by a combination of experimental and theoretical studies that the "unoccupied" p orbital of dioxaboryl ligands are intimately involved in the C-H bond activation step and that this hydrogen transfer to boron occurs by a bor on-assisted, metal-mediated sigma-bond metathesis.

Borylation and silylation of C-H bonds: a platform for diverse C-H bond functionalizations.

  • J. Hartwig
  • Chemistry
    Accounts of chemical research
  • 2012
The fundamental principles that govern the reactivity of intermediates containing metal-boron bonds are emphasized and how an understanding of the effects of the ligands on this reactivity led us to broaden the scope of main group reagents that react under mild conditions to generate synthetically useful organosilanes is described.

Importance of palladium-carbon bond energies in direct arylation of polyfluorinated benzenes.

It is found that the key aspects of the reactions are the lowering of the energy of the CMD step by the ortho fluorine substituents, the regioselective activation of C-H bonds ortho to fluorine which is also determined at the C MD step, and the decoordination of AcOH, which maintains the transition state for reductive elimination at low Gibbs free energy.

Carboxylation of organoboronic esters catalyzed by N-heterocyclic carbene copper(I) complexes.

An excellent N-heterocyclic carbene copper(I) catalyst system for the carboxylation of aryland alkenylboronic esters with CO2 is reported, which not only showed higher functional-group tolerance, but could also afford structurally characterizable active catalyst species, thus offering unprecedented insight into the mechanistic aspects of the catalytic process.