A new and in situ formed reagent generated by mixing PIFA {bis[(trifluoroacetoxy)iodobenzene]} and AlCl3 was introduced in the organic synthesis for the direct and highly regioselective ortho‐chlorination of phenols and phenol ethers. An efficient electrophilic chlorination for these electron‐rich arenes as well as the scope of the reaction are described herein. An easy, practical, and open‐flask reaction allowed us to introduce a chlorine atom, which is a highly important functional group in organic synthesis. The reproducibility of our method has been demonstrated on gram‐scale by carrying out the reaction in 6‐bromo‐2‐naphthol. This halogenation reaction also proceeds in excellent conditions by first preparing the iodine(III)‐based chlorinating reagent. Our new chlorinating reagent can be stored at least for two weeks at 4 °C without losing its reactivity.
A practical electrophilic bromination procedure for the phenolic core was developed under efficient and very mild reaction conditions. The new I(iii)-based brominating reagent PhIOAcBr operationally easy to prepare by mixing PIDA and AlBr3 was used.
The oxidative activation of alkyl C-H bonds vs arene C-H bonds with Pd(OAc) 2 has been found to be generalizable to a number of nucleophilic substrates allowing the formation of a range of hindered quaternary centers. The substrates share a common mechanistic path wherein Pd(II) initiates an oxidative dimerization. The resultant dimer modifies the palladium catalyst to favor activation of alkyl C-H bonds in contrast to the trends typically observed via a concerted metalation deprotonation mechanism. Notably, insertion occurs at the terminus of the alkyl arene for hindered substrates. Two different oxidant systems were discovered that turn over the process. Parameters have been identified that predict, which substrates are productive in this reaction.
The
first example of metal-free cyanomethylenation from alkyl nitriles
of sp3 C–H bonds to afford quaternary carbon centers
is described. This oxidative protocol is operationally simple and
features good functional group compatibility. This method provides
a novel approach to highly functionalized fluorene and oxindole derivatives,
which are commonly used in material and pharmaceutical areas. Control
experiments provide evidence of a radical reaction process.
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