Asymmetric Migratory Tsuji-Wacker Oxidation Enables the Enantioselective Synthesis of Hetero- and Isosteric Diarylmethanes.

Diarylmethanes play, in part, a pivotal role in the design of highly potent, chiral, nonracemic drugs whose bioactivity is typically affected by the substitution pattern of their arene units. In this context, certain arenes such as -substituted benzenes or unsubstituted heteroarenes cause particular synthetic challenges, since such isosteric residues at the central methane carbon atom are typically indistinguishable for a chiral catalyst. Hence, the stereoselective incorporation of isosteric (hetero)arenes into chiral methane scaffolds requires the use of stoichiometrically differentiated building blocks, which is typically realized through preceding redox-modifying operations such as metalation or halogenation and thus associated with disadvantageous step- and redox-economic traits.

Unimolecular net heterolysis of symmetric and homopolar σ-bonds.

The unimolecular heterolysis of covalent σ-bonds is integral to many chemical transformations, including S1-, E1- and 1,2-migration reactions. To a first approximation, the unequal redistribution of electron density during bond heterolysis is governed by the difference in polarity of the two departing bonding partners. This means that if a σ-bond consists of two identical groups (that is, symmetric σ-bonds), its unimolecular fission from the S, S, or T states only occurs homolytically after thermal or photochemical activation.