Preview

PDF, English Download (7MB) | Terms of use

Abstract

The thesis is focused on hydroxylamine-mediated direct arene C-H amination and C-C amination from benzyl alcohols, alkylarenes, styrenes and benzyl ethers/esters, which are used for the anilines synthesis. Additionally, this thesis consists of three parts.

In the first part (Chapter 2), a direct metal-free arene C-H amination mediated by hydroxylamines (TsONHBoc or TsONHR) was discovered, accidentally. Besides one literature reported with only three examples, this is the only report for an aniline synthesis via hydroxylamine derivatives under metal-free conditions. Primary anilines and secondary anilines are afforded under open flask conditions with this protocol, by using TsONHBoc or TsONHR, respectively. In contrast to metal-catalyzed processes, the reaction is triggered by an oxygen-accelerated SET (single electron transfer) from the aromatic systems to the electron-deficient hydroxylamine derivatives. The recombination of an arene radical cation and an aminyl radical, which are in close proximity, then affords the aminated products. The methodology can be applied for the amination of a variety of complex molecules, natural bioactive products and bestselling drugs. The operationally easy, broad functional group tolerance and scalability of this reaction in the absence of any metal make it appealing for both academy and industry.

The second part (Chapter 3) describes an aza-Hock rearrangement of benzyl alcohols by using hydroxylamines (ArSO2ONHR) as reagents under mild conditions, which makes primary anilines accessible from O-(2,4,6- trimethylbenzenesulfonyl)hydroxylamine (MSH) and secondary anilines available from other aminating reagents like TsONHR. Mechanistically we could prove that an aza-Hock rearrangement operates. Other benzyl cation precursors (eg. benzyl ethers/esters/halides and alkylarenes) are also potent substrates for this strategy, expanding the synthetic utility. In addition, chemoselective C-C brominations and oxygenations are possible under similar conditions. Interestingly, despite some early evidence for such a reactivity pattern, until now the synthetic utility of this process is limited and our report might pave the way for further protocols based on such pattern in the future.

A modified aza-Hock rearrangement of benzyl cation precursors – alkylarenes, styrenes and benzyl ethers/esters – mediated by hydroxylamines, was investigated in the third part (Chapter 4). Notably, i-alkylarenes are differentiated by the aminating reagent MSH over n-alkylarenes, and n-alkylarenes are smoothly converted into anilines with TsONHMe. This rare phenomenon points out a way to distinguish different kinds of alkylarenes with such a pattern. Moreover, aminodealkenylation (C-C amination of styrenes) opens a gateway for employing styrenes in a plethora of known benzyl cation transformations, which should serve as a valuable tool for anilines synthesis, adding to the growing catalogue of C-C functionalization.