The use of pre-installed directing groups has become a popular and powerful strategy to control site selectivity in transition metal catalysed C–H functionalisation reactions. However, the necessity for directing group...
Transient directing groups (TDGs) can provide a powerful means for C−H functionalization without requiring additional steps for directing group introduction and removal. We report the first use of a TDG in combination with copper to effect C−H functionalization. The regioselective copper mediated β−C(sp2)−H sulfonylation of aldehydes with sulfinate salts is accomplished using catalytic β‐alanine to form a transient imine. A broad range of sulfonylated benzaldehydes are prepared using copper fluoride as both copper source and oxidant, involving a [5,6] cupracyclic intermediate. γ‐(peri)‐Sulfonylation of napthyl and phenanthrenyl carboxaldehydes is achieved through [6,6] cupracyclic intermediates. Further derivatisation of the aldehyde products is demonstrated. Kinetic experiments and Hammett analysis suggest the turnover limiting step to be a concerted asynchronous C−H cleavage via a dearomative Wheland‐type transition state.
Transient directing groups can provide a powerful means for C–H functionalization to install medicinally valuable motifs without requiring additional steps for directing group introduction and removal. Here we report the first use of a transient directing group in combination with copper to effect C-H functionalization. The copper mediated β–C(sp2)–H sulfonylation of aldehydes with sulfinate salts is accomplished using β-alanine, in catalytic quantities, to form a transient imine. A broad range of sulfonylated benzaldehydes are prepared using copper fluoride as both copper source and oxidant, involving a [5,6] cupracyclic intermediate. The transient directing group provides exclusive regioselectivity in C–H functionalization, even in the presence of other strongly coordinating Lewis basic groups. In addition, gamma-(peri)-sulfonylation of napthyl and phenanthrene carboxaldehydes is achieved through [6,6] cupracyclic intermediates. Further derivatisation of the aldehyde products is demonstrated. Mechanistic studies, including deuteration and kinetic experiments, which identify orders in all reagents, provide insight to the catalytic behaviour of the amine. Kinetic isotope effect experiments and Hammett analysis suggest the turnover limiting step to be a concerted asynchronous C–H cleavage via a dearomative Wheland-type transition state.
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