Synthesis and Characterization of Cobalt-NHC Complexes: Application in Regioselective Hydroboration of Unsaturated Compounds

Abstract

Boronic acid(esters) have been recognized as an indispensable coupling partner in several cross-coupling reactions, producing a vast spectrum of molecules applicable in diverse fields, from medicinal to materials sciences.[1] Transition metal-catalyzed synthesis of boronic esters from pinacolborane is a well-established methodology.[2] Even though precious metals have played a central role in achieving the transformation, research on the catalytic potential of base metals has started emerging recently. Therefore, developing robust catalytic methods using low-valent cobalt complexes to synthesize boronic esters from organic compounds is challenging.

In the first section, a general procedure for synthesizing a variety of carbene salt precursors using a convenient technique is developed. The extended protocol of a solvent-free approach for synthesizing various bridged bis-imidazolium carbene salts, including tris- and tetrakis-imidazolium precursors, will be described here. Several new Co-NHC complexes were prepared without generating the free carbene using the procedure described herewith. [3]

The second section deals with the ligand-controlled catalytic synthesis of 1,2 dihydro-N-heteroarenes. The in situ generated Co-NHC complex acts as a catalyst, reacts with N-heteroarenes and pinacolborane (HBpin), and produces the corresponding 1,2 dihydro-N-heteroarenes. The choice of sterically demanding N-heterocyclic carbene ligands led to the 1,2-regioselectivity. The preliminary mechanistic studies corroborate that the two ligands followed a distinct catalytic cycle with Co(I) as an active species.[4]

The third section describes the development of regioselective hydroboration of unsymmetrical internal alkynes. The pincer NHC-based Co complex catalyzes the cis-α selective hydroboration of unactivated internal alkynes and the cis-β selective hydroboration of activated internal alkynes with pinacolborane. High chemo-, regio-, and stereoselectivity were showcased in the reaction under base-free reaction conditions with a very low loading of the catalyst. Mechanistic studies suggest a feasible Co-boryl intermediate to explain the unusual regioselectivity.[5]

The last section describes the ligand-controlled cobalt-catalyzed regio-divergent synthesis of vinyl-boronic ester and alkyl-boronic ester via the hydroboration of unactivated enynes. The tridentate-NHC ligated Co(I) complex selectively produced vinyl-boronic ester, whereas the alkyl-boronic ester can be synthesized by changing the ligand to a bis-N-heterocyclic carbene. Mechanistic studies revealed that the formation of two different intermediates selectively hydroborates the enynes, producing different boronic esters in a regio-divergent fashion.[6]

References:

[1] Boronic Acids-Preparation and Applications in Organic Synthesis, Medicine and Materials, 2nd ed.; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2011.

[2] Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B. Chem. Rev. 2016, 116, 9091-9161.

[3] Meher, N. K.; Kashyap, A.; Geetharani, K. Chem. Asian J. 2024, e202401085.

[4] Meher, N. K.; Verma, P. K.; Geetharani, K. Org. Lett. 2023, 25, 87–92.

[5] Meher, N. K.; Suryavansi, M.; Geetharani, K. Org. Lett. 2024, 26, 5862–5867.

[6] Meher, N. K.; Geetharani, K. Manuscript under preparation.