Aniline derivatives are frequently encountered in molecules of industrial relevance such as dyes or antioxidants, which make the development of synthetic methods for the functionalization of these privileged structures highly sought-after. A general protocol for the hydroarylation of electronically diverse alkenes with anilines would be ideal to provide densely functionalized compounds. Yet, this transformation has been underexplored compared to more traditional hydroarylation of unactivated alkenes because of the significant challenges associated with the control of the selectivity and its substrate tolerance. Herein, we describe a selective, versatile and user-friendly ortho-C-alkylation of anilines with alkenes that hinges on the beneficial combination of a Lewis acid (Ca(II)) and hexafluoroisopropanol as a solvent. This protocol allows for the extension of this transformation to highly deactivated styrenes and demonstrates a remarkable improved reactivity regarding aliphatic alkenes, styrene derivatives and dienes. In addition, DFT computations were performed which, combined with experimental observations, suggest a nearly concerted mechanism that impart the ortho-selectivity.
Pyrrolidine and piperidine derivatives bearing halide functional groups are prevalent building blocks in drug discovery as halides can serve as an anchor for postmodifications.I np rinciple,o ne of the simplest ways to build these frameworks is the haloamination of alkenes.W hile progress has been made in this field, notably with the development of enantioselective versions,t his reaction is still fraught with limitations in terms of reactivity.Besides,amajor question remaining is to understand the mechanism at work. The formation of ah aliranium intermediate is typically mentioned, but limited mechanistic evidence supports it. Reported here is an efficient metal-and oxidant-free protocol to achieve the haloamidation of olefins,p romoted by hexafluoroisopropanol, along with aD FT investigation of the mechanism. These findings should guide the future development of more complex transformations in the field of halofunctionalization.
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