Access to ALPHA-Boryl Radicals from 1,1-Diboronates

Organic chemistry concerns itself with the synthesis and application of molecules primarily composed of carbon and hydrogen atoms. As such, organic compounds are the main components of all living matter and are therefore of high importance for medicinal, biochemical and agrochemical purposes. The synthesis of organic molecules is primarily focused on the formation of new carbon carbon (CC) bonds further functionalisation, for example through oxidations or reductions, subsequently leads to the desired products. Carbon-based molecules containing boron are commonly referred to as organoboron compounds. In these molecules, the boron atom is bound covalently to one carbon atom (BC) and is also, in most cases, connected to two oxygen atoms by two separate bonds (BO). The functional boron-group is capable of promoting the aforementioned CC bond-formation (often, but not exclusively, catalysed by transition metals); but other elementsso-called heteroatomscan also be introduced through activation of the boroncarbon bond. Remarkably, these transformations can also be conducted in a stereospecific manner. Stereospecificity entails the retention of the three-dimensional (stereochemical) structure and information of the substrate and as such stereospecific transformations are a main focus of attention of modern synthetic chemistry. The versatility of organoboron compounds renders them highly valuable synthetic intermediates and the group of Prof. Varinder K. Aggarwal at the University of Bristol has devoted decades of research to their formation and synthetic use. The aim of this project is to assemble synthetically useful organoboron compounds via a novel approach photoredox catalysis. Photoredox catalysis harnesses the energy of light for the activation of catalysts which, down the line, effect the desired transformations. In this specific case, the controlled decay of mixed 1,1-diboronates is to be induced by an activated photocatalyst, generating a-boryl radicals. These resulting species can then be coupled with select substrates by various different methods, generating novel and valuable organoboron compounds. The synthetic advantage of this new approach lies in the catalytic nature of the process (avoiding the use of large quantities of reagents) and also in the mild reaction conditions that allow the desired transformation to proceed even with highly sensitive substrate molecules.

To our initial disappointment, it became apparent quite early that the originally sought transformation would be exceedingly hard to achieve. For this reason, we shifted the focus of our investigations from 1,1 diboronates to 1,2-diboronates. The general approach and the connected research question, however, remained the same: Is it possible to generate radicals from diboronates using photoredoxcatalysis and can these radicals be converted into functionalized boron-containing products? In contrast to 1,1-diboronates, in which both boron substituents are identical, 1,2-diboronates pose an additional challenge in the context of regioselectivity. In order to develop a synthetically useful transformation, it is imperative that only one of the two boron substituents be activated and subsequently functionalized. To our delight, by choosing a sterically demanding activating agent, the selective activation of the more accessible boron substituent was possible. We thus reasoned that the radical resulting from oxidation with a photoredoxcatalyst would engage in a carbon-carbon bond-forming reaction at this less substituted (and therefore more accessible) position of the former 1,2-diboronate. Following activation, the intermediate was, according to the original plan, subjected to photoredox oxidation and subsequent functionalization. Surprisingly, our initial investigations revealed the opposite regioselectivity to that which we had expected, functionalizing the more hindered carbon atom. Owing to the obvious selectivity of the activation step (which we would go on to prove using isotopic labelling studies), we concluded that the reaction must proceed via a 1,2-boron shift with concomitant migration of the radical. While similar processes are known for related classes of compounds, the homolytic 1,2-boron shift is wildly underrepresented in the literature - to the best of our knowledge, there had been only one previous report of such a transformation on somewhat more specialized molecular frameworks. The discovery of this unusual process allowed us to further investigate new approaches for the functionalizations of hindered positions. The products thus obtained, in some cases having evolved through complex rearrangements and fragmentations, are characterized by high yields, regioselectivities and, in some cases, stereoselectivities. Additional exploration of the potential scope of this 1,2-boron shift is underway and novel synthetic routes to products of added value and complexity are currently being developed.