One‐Pot C−H Functionalization of Arenes by Diaryliodonium Salts

Abstract

Atransition-metal-free,mild, and highly regioselective synthesis of nitroarenes from arenes has been developed. The products are obtained in asequential one-pot reaction by nitration of iodine(III) reagents with two carbon ligands,which are formed in situ from iodine(I). This novel concept has been extended to formation of aryl azides,a nd constitutes an important step towards catalytic reactions with these hypervalent iodine reagents.Anefficient nitration of isolated diaryliodonium salts has also been developed, and the mechanismis proposed to proceed by a[ 2,2] ligand coupling pathway.Hypervalent iodine compounds have become important reagents for aw ide variety of transformations,a st hey have avaluable combination of properties including high reactivity, high functional-group tolerance,and low toxicity.[1] Themain drawback with hypervalent iodine reagents is the stoichiometric formation of either an iodine(I) or iodine(III) compound as waste,d epending on the oxidation state (III or V) of the starting reagent. This aspect lowers the atom efficiency and may lead to product purification problems.The groups of Ochiai and Kita reported the first catalytic uses of hypervalent iodine reagents in 2005 (Scheme 1a).[2] Since then many other systems have appeared, where ac atalytic amount of iodoarene is combined with as toichiometric amount of an oxidant.[3]Iodonium salts and their cyclic counterparts benziodoxol-(on)es (e.g. EBX and Tognis reagent) are important iodine(III) reagents for the transfer of carbon ligands (aryl, alkynyl, vinyl, CF 3 ,o rC Ng roups) to aw ide range of nucleophiles.[4] These reagents are generally synthesized in one or more steps,i solated, and subsequently reacted with an ucleophile.K ita and co-workers have demonstrated the efficient in situ formation of diaryliodonium salts from other iodine(III) reagents in metal-free arylations (Scheme 1b), [5] and the group of Suna has utilized the same strategy in metalcatalyzed arylations.[6] However,tothe best of our knowledge, catalytic reactions with iodonium salts or benziodoxol(on)es remain unknown. [4,7] In our long-term quest for catalytic arylation conditions, we reasoned that in situ formation of diaryliodonium salts from arenes and iodoarenes in the presence of an oxidant, followed by arylation of as uitable nucleophile under metalfree conditions,w ould constitute an important step towards this difficult goal. Herein we present our results of an efficient arylation of sodium nitrite with diaryliodonium salts,w hich can be formed in situ from arenes and iodoarenes under oxidative conditions (Scheme 1c). Them ethodology compares well to previous routes to nitroarenes,c oncerning regioselectivity,f unctional-group tolerance,a nd ease of handling. [8] Synthetic routes to aromatic nitro compounds are important, as nitroarenes are key intermediates in the preparation of many dyes,p lastics,a nd explosives.[9] They can be synthesized from arenes under harsh acidic conditions, [9a] by treatment with [bis(trifluoroacetoxy)iodo]benzene...

Site Selective Concerted Nucleophilic Aromatic Substitutions of Azole‐Ligated Diaryliodonium Salts

“…Here, electronic factors were more important, and nitration of electron‐deficient aryl moieties predominated [15a–b,f] . Other studies have noted a strong influence of the ortho ‐effect on the chemoselectivity of ortho ‐substituted iodonium salts, despite competing electronic preferences [15c–e] . In our case, the selectivity is determined by the presence of azaheterocylic substituents.…”

“…The envisioned one‐pot sequence was investigated next. An efficient arylation of sodium nitrite with diaryliodonium salts, which can be formed in situ from arenes and iodoarenes under oxidative conditions, has been previously reported [15e] . In contrast to this initial report, the newly developed nucleophilic nitration with N ‐stabilized iodonium salts can be implemented without the isolation of intermediates by removing solvents under reduced pressure at each stage.…”

“…A variety of benzimidazole‐derived iodonium salts 4 a – 4 i were selectively nitrated in consistently high yields (up to 99%). However, it is worth noting that to achieve complete conversion for benzoxazole and benzimidazole derivatives 4 c – 4 h , additions of NaOTf [15e] (1.0 equiv.) or an additional amount of NaNO 2 , or both, were required.…”

Cu-Mediated C–H 18F-Fluorination of Electron-Rich (Hetero)arenes

“…As shown in Scheme 2 , ArI III X 2 salts are known to participate in site-selective S E Ar reactions with electron-rich (hetero)arenes. 11 − 13 Furthermore, these transformations yield diaryliodonium salts, which we have shown to undergo Cu-catalyzed radiofluorination with [ 18 F]KF. 3a , 14 While electron-rich diaryliodonium salts are notoriously unstable, 5a , 15 this approach offers the advantage that they are generated in situ from stable and readily available C–H starting materials.…”

“…Furthermore, 2a is known to undergo Cu-catalyzed radiofluorination with [ 18 F]KF. 3a , 13 , 14 , 17 There were two key considerations for our choice of aryliodonium electrophile and activator for this one-pot radiofluorination. First, these reagents should not contain nucleophilic counterions ( Y ) (e.g., carboxylates), as these are susceptible to undesired coupling reactions with the diaryliodonium intermediate 2 ( eq 1 ).…”