Alkylboronic Esters as Radical Precursors: Applications to Deboronative Radical Chain Reactions

Many efforts have been made in developing valuable transformations taking advantage of the electron deficiency caused by the vacant p-orbital of boron and the metallic properties of its derivatives. Organoboron derivatives have proven over the years to be a versatile source of alkyl radicals. The generation of carbon-centered radicals from air-sensitive B-alkylcatecholborane through nucleohomolytic substitution at boron is well-established and became a general method to generate alkyl radicals. The high reactivity of catechol alkylboronic esters towards heteroatom-centered radical (e.g. O2) causes stability issues for purification processes and long-term storages. However, the generation of radicals from bench-stable boronic esters such as pinacol alkylboronic esters is not suitable due to their reduced Lewis acidity and lack of radical resonance-stabilization. Our studies focused on an in situ conversion of pinacol alkylboronic esters into catechol alkylboronic esters, achievable by boron-transesterification. This transformation was tailored to various radical chain deboronative processes enabling C—X, C—S, C—C and C—H bonds formation . Besides, we investigated the in situ boron-transesterification using further bench-stable boronic ester precursors, i.e., norbornanediol boronic esters. Ultimately, we applied this chemistry to the underdeveloped anti-Markovnikov hydromethylation of unactivated alkenes by merging an iodine atom transfer radical addition (I-ATRA) of norbornanediol iodomethyl boronate (ICH2Bnor) onto unactivated alkenes, and the previously exploited protodeboronative radical chain process. Additionally, the generation of cyclic and acyclic 1-alkoxyalkyl radicals was explored using our deboronative approach from pinacol alkoxyalkylboronic esters. The synthetic utility of our method was thoroughly studied, allowing the synthesis of 2-alkylated tetrahydrofurans (THF) and tetrahydropyrans (THP) using various radical chain deboronative processes, the hydroalkoxymethylation of Michael acceptors, and the construction of substituted-THF ring systems through radical cyclization