Nucleophilic Boron Chemistry: Catalytic approaches to C-X (X= Br, Cl, O, N) Bond Activation in Metal/Metal-free Conditions

Abstract

The boron-carbon bond occupies a central position in organic synthesis, functioning as a versatile “universal connector” to a broad range of functional groups. As a result, organoboranes have become indispensable synthetic tools, motivating continued efforts to develop precise and efficient methods for incorporating boryl groups into organic frameworks. Over the past two decades, advances in nucleophilic-boron chemistry have reshaped our understanding of boron reactivity, challenging its classical role as a Lewis acid. Through strategic ligand design and base activation, boron centers can be rendered electron-rich, unlocking reactivity patterns that complement traditional organoborane chemistry. Despite this progress, achieving controlled boryl-group transfer and high catalytic efficiency remains a significant challenge.

In this thesis, we first demonstrate the use of iron complexes to achieve the borylation of alkyl halides under mild conditions, obviating the need for strongly basic organometallic reagents. Employing an Fe(II) bis(amide) complex together with bis(neopentylglycolato)diboron (B₂neop₂), the reaction proceeds through a radical pathway, as supported by TEMPO-trapping and radical-clock experiments. The proposed mechanism involves the formation of iron–boryl intermediates followed by single-electron transfer (SET) steps that generate alkyl radicals, which subsequently couple with boronate nucleophiles to forge C-B bonds.

We next report a metal-free protoboration of dialkyl ketones that delivers α-hydroxy boronates and effectively reverses the regioselectivity typically observed in hydroboration reactions. This transformation proceeds through a nucleophilic-boron mechanism in which the boron reagent activates the carbonyl group via a concerted pathway, affording products in high yield and with excellent chemoselectivity. Given the synthetic importance of α-amino boronates, we extended this method to customized dialkyl ketimines, enabling their direct conversion into valuable α-amino boronate esters. Finally, we explored hydroboration and homologation strategies on these ketimines to access β-amino boronate esters, further broadening the synthetic utility of boron-based methodologies.