StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) is provided by the cyclophane substituent on iodine(III). Computational and experimental studies demonstrate that out of plane steric bulk strongly destabilizes the reductive elimination transition state, and leads to regiochemical control. This approach should be general for high valent main group and transition metal ions.

For the first time it is shown that exceptionally electron-rich arene rings can be fluorinated exclusively during the reductive elimination reactions of diaryliodonium fluorides. The 5-methoxy[2.2]paracyclophan-4-yl directing group simultaneously reduces unproductive aryne chemistry and eliminates ligand exchange reactions by a combination of steric and electronic effects. Use of the cyclophane directing group permits an unprecedented degree of control in fluorination reactions of diaryliodonium salts.

StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) is provided by the cyclophane substituent on iodine(III).Computational and experimental studies demonstrate that out of plane steric bulk strongly destabilizes the reductive elimination transition state, and leads to regiochemical control. This approach should be general for high valent main group and transition metal ions.Keywords reductive elimination; stereoelectronic effects; regiochemistry; iodanes; cyclophanes Diaryliodonium salts are useful precursors for arylation of diverse carbon and heteroatom nucleophiles. [1][2][3][4] In practice, poor regioselectivity for reductive elimination narrows the synthetic scope of diaryliodonium salts (Scheme 1). Efficient conversion is best obtained when two identical aryl substituents are on I(III), however, the preparation of symmetrical diaryliodonium salts can be problematic and uneconomical. [11] For relatively complex aromatic molecules, the tandem synthesis and protection of the oxidized (I(III)) and reduced (organometallic) coupling partners necessary to prepare the symmetrical diaryliodonium salt is often a significant challenge, and purification of the functionalized product from the reductively eliminated aryl iodide can prove difficult.In the thermal decomposition of unsymmetrical diaryliodonium salts, the identity of the aryl iodide reductively eliminated is typically dictated by electronic effects; the electron-rich aryl iodide and the functionalized electron-poor aromatic compound are formed predominantly (Scheme 1). Selectively functionalized electron-rich aromatic rings are often the desired target compounds, but extremely electron-rich diaryliodonium salts are prone to side reactions involving redox and inner-sphere electron transfer, thus there is a limit to using electronic control to achieve regioselectivity.We sought a universal "locked" aryl substituent that would result in StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) from diaryliodonium salts. Since electronic effects cannot be used exclusively to achieve this end, steric and/or stereoelectronic effects must be exploited to gain regiocontrol of reductive elimination. Here we show that the use of cyclophane-derived iodonium salts permits regiospecific reductive elimination (Scheme 2).The impact of steric effects upon reductive elimination in diaryliodonium salts has been investigated in some detail. Aryl methyl substituents ortho to the I(III) center offer a modest acceleration in elimination rates, so that there is a slight preference for the more highly substituted product to be functionalized (Scheme 1). [7,12] "ortho effect" are: 1) the more sterically demanding aromatic ring prefers an equatorial position syn to the nucleophile, and 2) the ortho-substituted aromatic is more likely to prefer a conformation in which the p-system is more likely to align with the incoming nucleophile. [13][14][15] In an exception to this rule, Ochiai and coworkers have shown that for binaphthyl aryl iod...