Enhancing triethylborane initiation through mechanistic understanding

Triethylborane (Et3B) in the presence of O2 is one of the most widely used systems for radical chain initiation in organic synthesis. However, its initiation mechanism is poorly understood, and some reactions fail to initiate by this system. In this work we uncovered an obscure, previously unknown secondary mechanism of initiation using a novel radical trapping technique. We utilised a new radical trap capable of capturing free radicals generated during initiation to allow their detection by mass spectrometry (MS) and quantification by nuclear magnetic resonance (NMR). This technique was applied to investigate the reactions involved in the initiation mechanism of Et3B/O2 system. We confirmed that the primary initiation mechanism generates ethyl radicals as the initiating radicals. However, as predicted by our kinetic simulations, the primary mechanism is very inefficient, and it is unlikely to account for the initiation alone. We hypothesised that diethyl(ethylperoxy)borane (Et2BOOEt), the product of autoxidation, plays an important role in initiation. We synthesised Et2BOOEt separately and reacted it with Et3B in the presence of the radical trap. It was found that this reaction generated 1 eq. of ethyl radicals, which were identified by MS and quantified by NMR. Our findings suggest that Et3B/Et2BOOEt acts as a more efficient initiator than Et3B/O2 as the initiation proceeds. When this mechanism was simulated computationally it was found the secondary initiation produces 7 x 104 times more initiating radicals than the primary initiation. We exploited this insight to overcome the challenges of initiation by using Et2BOOEt in combination with Et3B to initiate inefficient chains that could not be accessed using Et3B/O2 alone. This work demonstrates the power of our novel radical trapping technique for studying complex radical mechanisms while further expanding our understanding of Et3B/O2 initiation, facilitating its application and opening new avenues for exploration in organic synthesis.