The first examples of Rh-catalyzed asymmetric C-H insertions involving a donor-donor diaryl rhodium carbenoid are reported. The carbenoid precursor, a diazo compound, is formed in situ by MnO2 oxidation of a diaryl hydrazone. A chiral catalyst, Rh2(R-PTAD)4, is added in one pot to afford various benzodihydrofurans in high diastereo- and enantioselectivity. Highlights of this reaction include: excellent yields of up to 95%, dr >95:5 and er up to 99:1 with a wide functional group tolerance. The reaction is also amenable to scale-up and low catalyst loading (0.1 mol %). The benzodihydrofuran core formed in the C-H insertion reaction is an important structure that is seen in many natural products, such as resveratrol derivatives. Some resveratrol-derived natural products are known to have useful antibiotic and antifungal properties. Synthetic efforts towards these compounds have largely been limited to enzymatic transformations and racemic syntheses. We have applied our new C-H insertion methodology toward the first example of an asymmetric synthesis of a resveratrol derivative, E-d-viniferin. This synthesis involves a late stage C-H insertion of a diaryl diazo intermediate. The methodology and synthetic work presented here provides access to the efficient and enantioselective synthesis of compounds not previously accessible by available synthetic methods.

Asymmetric synthesis of benzodihydrofurans via C-H insertion of diaryl rhodium (II) carbenoids

248th National Meeting (2014)

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