Asymmetric radical-mediated transformations are highly desirable yet rarely realized, as it is challenging to maintain meaningful catalyst associations with high energy open-shell intermediates. Proton-coupled electron transfer (PCET) is an unconventional redox mechanism in which a radical species is generated within a hydrogen-bonded interface, providing a unique handle for enantioselective radical catalysis. Here, we report the synthesis of enantioenriched pyrroloindoline products using a PCET strategy in which a photoredox catalyst and chiral Brønsted base act jointly in the oxidation of tryptamine to provide a key H-bonded indolyl radical intermediate. This species is quickly trapped by TEMPO● to produce C<sub>3</sub>-functionalized pyrroloindoline products with high yields and enantioselectivities. These enantioenriched ‘TEMPO-lated’ pyrroloindolines are valuable synthetic intermediates as subsequent one-electron oxidation and mesolytic C-O bond cleavage reveals a configurationally-biased pyrroloindoline carbocation able to react with a wide range of nucleophiles in a stereoretentive fashion. This work provides facile access to a variety of pyrroloindoline natural products and highlights concise enantio- and diastereoselective routes to (-)-chimonanthine and (-)-calycanthidine.

Enantioselective photoredox catalysis enabled by proton-coupled electron transfer: Development of a concise, asymmetric synthesis of pyrroloindoline alkaloids

255th National Meeting (2018)

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