A designed new class of modifiable sulfur tethers for aromatic CH bond functionalizations is presented. As a model, the palladium-catalyzed directed acetoxylation reaction was studied. The more challenging sulfoxide tethers were the most effective in this transformation, showing a broad functionality tolerance, high S oxido-redox stability and no catalyst poisoning. Preliminary mechanistic studies indicate that the higher reactivity and selectivity shown by the sulfoxide tethers vs. the corresponding sulfones can be attributed to an extra coordination of the sulfoxide S atom to the catalyst. The utility of the presented methodology to generate structurally interesting aromatic derivatives by a subsequent modification of the S-tether is also exemplified.

The cross dehydrogenative coupling (CDC) of cyclic benzyl ethers with aliphatic and α,β-unsaturated aldehydes has been developed. The mild reaction conditions, in which an N-oxoammonium salt derived from TEMPO (2,2,6,6-tetramethyl-1-piperidinoxyl) is employed as the oxidant in combination with a Cu catalyst, allow the use of relatively redox-unstable aldehydes under oxidative CDC conditions. The addition of a catalytic amount of trifluoroacetic acid (TFA) or Ac₂O facilitates the reaction and increases the efficiency and selectivity. In contrast to the expected α-alkylation obtained with aliphatic aldehydes, α,β-unsaturated aldehydes led preferentially to the more challenging γ-alkylated products. The utility of the developed methodology was demonstrated by the synthesis of isochromane-derived bioactive compounds, such as the dopamine antagonist sonepiprazole.

The first oxoammonium salt mediated formation of C–C bonds from benzylic C(sp³)–H bonds adjacent to an oxygen or nitrogen atom by dehydrogenative coupling with enolizable carbonyls has been developed. The use of these oxidants in combination with catalytic amounts of Fe(OTf)₂ as Lewis acid allows the reaction to be carried out under mild conditions, leading to the corresponding coupling products in moderate to good yields.