Colson, EloïseEloïseColsonAndrez, JulieJulieAndrezDabbous, AliAliDabbousDénès, FabriceFabriceDénèsMaurel, VincentVincentMaurelMouesca, Jean-MarieJean-MarieMouescaRenaud, PhilippePhilippeRenaud0000-0002-9069-71092024-10-152024-10-152022-04-28https://boris-portal.unibe.ch/handle/20.500.12422/120934Tropanes and related bicyclic alkaloids are highly attractive compounds possessing a broad biological activity. Here we report a mild and simple protocol for the synthesis of N-arylated 8-azabicyclo[3.2.1]octane and 9-azabicyclo[3.3.1]nonane derivatives. It provides these valuable bicyclic alkaloid skeletons in good yields and high levels of diastereoselectivity from simple and readily available starting materials using visible-light photoredox catalysis. These bicyclic aniline derivatives are hardly accessible via the classical Robinson tropane synthesis and represent a particularly attractive scaffold for medicinal chemistry. This unprecedented annulation process takes advantage of the unique reactivity of ethyl 2-(acetoxymethyl)acrylate as a 1,3-bis radical acceptor and of cyclic N,N-dialkylanilines as radical 1,3-bis radical donors. The success of this process relies on efficient electron transfer processes and highly selective deprotonation of aminium radical cations leading to the key α-amino radical intermediates.en500 - Science::570 - Life sciences; biology500 - Science::540 - Chemistry000 - Computer science, knowledge & systemsarticle10.48350/1779143669788310.1038/s42004-022-00671-x