Hypervalent Iodine as Directing Tool in Iodine-Retentive Transformation of C-H Bonds

Identifier:  TDX:2723

Handle: https://hdl.handle.net/20.500.11797/TDX2723

Authors:  Wu, Yichen

Abstract:
The chemistry of organic hypervalent iodine compounds has been a potent and versatile toolbox in organic synthesis. In particular, organic λ3-iodanes have been utilized as terminal 2-electron oxidants, as well as group transfer agents in a wide range oxidative functionalization processes. With few exceptions, such transformations are accompanied by the liberation of the parent organoiodine fragment. A less explored, but synthetically attractive possibility consists in incorporating both the organic group and the iodine atom into the final product. Such approach presents a clear synthetic appeal, given that the iodine retention opens the door for downstream derivatization. This thesis describes a series of such “iodine-directed” coupling reaction employing organo-λ3-iodanes as substrates. In one approach, a new method for direct metal-free α-arylation of ketones is described. The aryl transfer takes place via the coupling ortho to iodine, and is based on in situ hypervalent activation of the iodine atom. The protocol shows good functional group compatibility on the arene core. The ortho-selectivity was rationalized by DFT calculations through an unusual low-barrier “iodonio-Claisen¨ process. We also developed a new approach for regioselective benzylation of the ArI(OAc)2 cores using benzyltrimethylsilane. Interestingly, the carbon-carbon coupling now takes place selectively at para position to the iodine atom. Finally, an approach for oxidative “iodoarylation” of imidazoles was uncovered. The procedure relies on an efficient activation of the parent NH-imidazole with ArI(OAc)2, followed by copper-catalyzed intramolecular 1,3 I-to-N aryl transfer to constitute the synthetically challenging N1-aryl-5-iodoimidazoles. The importance of this manifold resides in the ability of the 5-iodoimidazoles to act as precursors for a range of 1,5-substituted imidazoles.