Synthesis of difluoroalkyl-sulfoximines via a light-promoted atom transfer radical addition (ATRA) process

Sulfoximines are imine derivatives of sulfones for which there has been an increased interest in the last 20 years, because this moiety is present in several biologically active molecules, including marketed drugs and pesticides. For this reason, the research devoted to the synthesis of new molecules bearing this functionality has been increasingly growing in the past few years. On the other hand, the development of new compounds that can act as bioisosteres is another popular research field. In particular, it has been observed that the difluoromethylene group (-CF2-) acts a bioisostere of carbonyl groups (C=O) or oxygen atoms, with significant improvements in terms of efficacy, selectivity and pharmacokinetics of the drug analogue. Building on these grounds, the present thesis work merges these two fields of research: sulfoximines and the difluoromethylene unit as bioisostere, focusing on the development of a new synthetic method for the introduction of difluoroalkyl sulfoximine moieties into relevant synthetic targets and building blocks such as unactivated olefins. The first phase of the thesis project focused on the optimization process, using as model substrates the bromodifluoromethyl phenyl sulfoximine and 1-hexene. I managed to reach an isolated yield of 50% in the model reaction under the optimized reaction conditions. The second goal of the thesis project deals with the evaluation of the genrality of the process, modifying the structure of the olefin reagent to evaluate the tolerance of the reaction towards the introduction of new functional groups.