Borane-catalysed Alkyne Hydroboration
Nieto Sepúlveda, Eduardo
Within the past few decades, organoboron compounds have become essential intermediates in organic and medicinal chemistry due to their unique advantages and versatility. Many synthetic approaches have been utilised to prepare these useful compounds, including several catalytic systems and diverse hydroborating agents. The hydroboration of terminal alkynes is one of the more common routes that provides alkenylboron reagents, allowing regio- and stereo-selective installation of the boron. Alcoholysis of phosphine borane complex to generate a new metastable hydroborating agent has been studied. The effect of the alcohol and solvent used in the solvolysis reaction have been determined. The use of halogenated solvents removed the irreproducibility observed when an ethereal solvent is used on its own. Thus having a mixture of both solvents, produces an ideal media to stabilise dialkoxyborane species. All kinetic data obtained are consistent with a direct SN2-like mechanism. A plausible mechanism has been proposed where an inconsistent generation of an ionic active species is likely to be causing the irreproducibility in the kinetic stability of the intermediate HB(OEt) 2. The dicyclohexylborane-catalysed hydroboration of 4-fluoropheny-lacetylene with pinacolborane was used as a benchmark. The kinetic profile for all components, including intermediates and side-products, have also been established by using in situ 19F NMR kinetic analysis and simulation. Isotope entrainment and stoichiometric studies employing isotopic labelling were used to characterise key steps of the borane-catalysed hydroboration reaction. The experimental evidence used to propose a thorough mechanism were also backed up by density functional theory (DFT) calculations. The mechanism includes the first true transborylation step, responsible of the regeneration of the catalyst (HBCy2) via B-C-B transfer of the alkenyl group with retention of (E)-configuration.