Details

Autor(en) / Beteiligte

• Granados, Albert
• Cabrera-Afonso, María Jesús
• Escolano, Marcos
• Badir, Shorouk O.
• Molander, Gary A.

Titel

Thianthrenium-enabled sulfonylation via electron donor-acceptor complex photoactivation

Ist Teil von

• Chem catalysis, 2022-04, Vol.2 (4), p.898-907

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Sulfone-containing compounds are prevalent building blocks in pharmaceutical agents and other biomolecules, and they serve as key intermediates in the synthesis of complex scaffolds. During the past decade, several methods have been developed to access sulfones. These strategies, however, require the use of strong reaction conditions, limiting their substrate scope. Recently, visible-light-mediated transformations have emerged as novel platforms to access unprecedented structural motifs. This report demonstrates thianthrenium-enabled sulfonylation via intra-complex charge transfer to generate transient aryl- and persistent sulfonyl radicals that undergo selective coupling to generate alkyl- and (hetero)aryl sulfones under ambient conditions. This strategy allows retention of halide handles, presenting a complementary approach to transition metal-mediated photoredox couplings. Furthermore, this sulfonylation allows high functional group tolerance and is amenable to late-stage functionalization of complex biomolecules. Mechanistic investigations support the intermediacy of electron donor-acceptor (EDA) complexes. [Display omitted] •Efficient formation of C-SO2 bonds via visible-light-mediated EDA complex strategy•Simultaneous generation of a transient aryl and persistent sulfonyl radicals•Late-stage sulfonylation of highly functionalized bioactive compounds or pharmaceuticals•Atom economy: thianthrene leaving group reused to construct new thianthrenium salts Given their importance in medicinal chemistry, agrochemicals, and materials science, numerous methods have been developed for the synthesis of sulfones. Traditional strategies require the use of harsh reaction conditions or employ expensive catalysts. Recently, electron donor-acceptor (EDA) complex photoactivation has been enlisted as a powerful strategy in organic synthesis because it avoids the use of exogenous photosensitizers and allows rapid assembly of diverse structural motifs under ambient conditions. This report describes thianthrenium-enabled sulfonylation via intra-complex charge transfer to generate transient aryl and persistent sulfonyl radicals that undergo selective coupling. This strategy is amenable to late-stage functionalization and enables retention of halide handles that can be harnessed for further derivatization. An operationally simple sulfonylation of activated arenes was achieved to render privileged sulfone structures. This is enabled by a photoinduced electron donor-acceptor (EDA) complex strategy using thianthrenium tetrafluoroborates and sodium sulfinates under mild conditions. This strategy allows late-stage sulfonylation of relevant bioactive molecules, such as gemfibrozil or fenofibrate, as well as retention of halogen handles.